Abstract

Oocyte and embryo selection governs the success of assisted reproductive technologies. The imaging tools applied for selecting embryos may need to contain several key properties: noninvasiveness, high 3D resolution, and the contrast capability to provide as much information about the embryos as possible, such as spindle fibers, zona pellucida, and organelles. Currently adopted imaging techniques can only provide one or two of these desired properties and are with limited contrast of the embryos. Some image techniques can even damage the embryos. Previous studies have shown that harmonic generation microscopy (HGM), a virtual-transition based technology, can provide noninvasive imaging in zebrafish embryos with a sub-cellular 3D resolution and a millimeter penetration depth, and thus could be a suitable tool for future oocyte and embryo selection of assisted reproductive technologies. However to evaluate HGM in clinical use, the intrinsic contrast origin of the second harmonic generation (SHG) and third harmonic generation (THG) inside the mammal embryos has to be studied. In this work we performed HGM studies on the in vitro cultured mouse oocytes and embryos by combining the SHG and THG modalities, with a focus on the contrast origin evaluation. Through the noninvasive HGM imaging, we can clearly identify various structures in the whole oocytes and embryos, including spindle fibers, zona pellucida, polar bodies, cell membranes, and the laminated organelles in the cells. The origin of the THG contrast was further confirmed through the standard staining studies. Through SHG signals, we could not only observe the spindle fibers when the oocytes were arrested at metaphase II or during the cleavage of the embryos, but can also distinguish and analyze the thickness of the three layers of the zona pellucida. Combining two different higher-harmonic generation modalities, SHG and THG, HGM successfully revealed the subcellular structures of the whole mouse embryos with a high 3D spatial resolution.

© 2008 Optical Society of America

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2008 (1)

2007 (4)

C.-H. Yu, S.-P. Tai, C.-T. Kung, I.-J. Wang, H.-C. Yu, H.-J. Huang, W.-J. Lee, Y.-F. Chan, and C.-K. Sun, "In vivo and ex vivo imaging of intra-tissue elastic fibers using third-harmonic-generation microscopy," Opt. Express 15, 11167-11177 (2007).
[CrossRef] [PubMed]

J. Holte, L.  Berglund, K.  Milton, C.  Garello, G.  Gennarelli, A.  Revelli, T.  Bergh, "Construction of an evidence-based integrated morphology cleavage embryo score for implantation potential of embryos scored and transferred on day 2 after oocyte retrieval," Hum. Reprod. 22, 548-557 (2007)
[CrossRef]

G. FitzHarris, P. Marangos, and J. Carroll, "Changes in endoplasmic reticulum structure during mouse oocyte maturation are controlled by the cytoskeleton and cytoplasmic dynein," Dev. Biol. 305, 133-144 (2007).
[CrossRef] [PubMed]

M. Shribak, J. LaFountain, D. Biggs, and S. Inoué, "Quantitative orientation-independent differential interference contrast (DIC) microscopy coupled with orientation-independent polarization microscopy," Microsc. Microanal. 13, 10-11 (2007).
[PubMed]

2006 (1)

D. Debarre, W. Supatto, A. M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M. C. Schanne-Klein, and E. Beaurepaire, "Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy," Nat. Methods 3, 47-53 (2006).
[CrossRef]

2005 (5)

S.-W. Chu, S.-P. Tai, C.-L. Ho, C.-H. Lin, and C.-K Sun, "High-resolution simultaneous three-photon fluorescence and third-harmonic-generation microscopy," Microsc. Res. Tech. 66, 193-197 (2005).
[CrossRef] [PubMed]

Y. Shen, T. Stalf, C. Mehnert, U. Eichenlaub-Ritter, and H.-R. Tinneberg, "High magnitude of light retardation by the zona pellucida is associated with conception cycles," Hum. Reprod. 20, 1596-1606 (2005).
[CrossRef] [PubMed]

G. A. Thouas, A. O. Trounson, and G. M. Jones, "Effect of Female Age on Mouse Oocyte Developmental Competence Following Mitochondrial Injury,"Biol. Reprod. 73, 366 - 373 (2005).
[CrossRef] [PubMed]

V.  Barzda, C.  Greenhalgh, J. A. D. Au, S. Elmore, J. H. van Beek, and J. Squier, "Visualization of mitochondria in cardiomyocytes by simultaneous harmonic generation and fluorescence microscopy," Opt. Express  13, 8263-8276 (2005).
[CrossRef] [PubMed]

V. Barzda, "Visualization of mitochondria in cardiomyocytes by simultaneous harmonic generation and fluorescence microscopy," Opt. Express 13,8263-8276 (2005).
[CrossRef] [PubMed]

2004 (5)

J. P. de Bruin, M. Dorland, E. R. Spek, G. Posthuma, M. van Haaften, C. W. Looman, and E. R. te Velde, "Age-related changes in the ultrastructure of the resting follicle pool in human ovaries," Biol. Reprod. 70, 419-424 (2004).
[CrossRef]

J. Otsuki, A. Okada, K. Morimoto, Y. Nagai, and H. Kubo, "The relationship between pregnancy outcome and smooth endoplasmic reticulum clusters in MII human oocytes," Hum. Reprod. 19, 1591-1597 (2004).
[CrossRef] [PubMed]

C. Pelletier, D. L. Keefe, and J. R. Trimarchi, "Noninvasive polarized light microscopy quantitatively distinguishes the multilaminar structure of the zona pellucida of living human eggs and embryos," Fertil. Steril. 81, 850-856 (2004).
[CrossRef] [PubMed]

C.-K. Sun, S.-W. Chu, S.-Y. Chen, T.-H. Tsai, T.-M. Liu, C.-Y. Lin, and H.-J. Tsai, "Higher harmonic generation microscopy for developmental biology," J. Struct. Bio. 147, 19-30 (2004).
[CrossRef]

S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of ???(2)/???(3) tensors in submicron-scaled bio-tissues by polarization harmonics optical microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

2003 (4)

D. F. Albertini and S. L. Barrett, "Oocyte-somatic cell communication," Reproduction 61 (Suppl), 49-54 (2003).
[PubMed]

G. Fitzharris, P. Marangos, and J. Carroll, "Cell cycle-dependent regulation of structure of endoplasmic reticulum and inositol 1, 4, 5-trisphosphate-induced Ca2+ release in mouse oocytes and embryos," Mol. Biol. Cell 14, 288-301 (2003).
[CrossRef] [PubMed]

S. Cooke, J. P. P. Tyler, G. L. Driscoll, "Meiotic spindle location and identification and its effect on embryonic cleavage plane and early development," Hum. Reprod. 18,2397-2405 (2003)
[CrossRef] [PubMed]

S.-W. Chu, S.-Y. Chen, T.-H. Tsai, T.-M. Liu, C.-Y. Lin, H.-J. Tsai, and C.-K. Sun, "In vivo developmental biology study using noninvasive multi-harmonic generation microscopy," Opt. Express 11, 3093-3099 (2003).
[CrossRef] [PubMed]

2002 (5)

L. Liu and D. L. Keefe, "Ageing-associated aberration in meiosis of oocytes from senescence-accelerated mice," Hum. Reprod. 17, 2678-2685 (2002).
[CrossRef] [PubMed]

R. D. Moreno, G. Schatten, and J. Ramalho-Santos, "Golgi apparatus dynamics during mouse oocyte in vitro maturation: effect of the membrane trafficking inhibitor brefeldin A," Biol. Reprod. 66, 1259-1266 (2002)
[CrossRef] [PubMed]

J. V. Blerkom, P. Davis, V. Mathwig, and S. Alexander, "Domains of high-polarized and low-polarized mitochondria may occur in mouse and human oocytes and early embryos" Hum. Reprod. 17, 393-406 (2002).
[CrossRef] [PubMed]

P. Stoller, K. M. Reiser, P. M. Celliers, and A. M. Rubenchik, "Polarization-modulated second harmonic generation in collagen," Biophys. J. 82, 3330-3342 (2002).
[CrossRef] [PubMed]

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, and W. A. Mohler, "Three dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissues," Biophys. J. 82, 493-508 (2002).
[CrossRef]

2001 (2)

S.-U. Chen, Y.-R. Lien, Y.-Y. Cheng, H.-F. Chen, H.-N. Ho, and Y.-S. Yang, "Vitrification of mouse oocytes using closed pulled straws (CPS) achieves a high survival and preserves good patterns of meiotic spindles, compared with conventional straws, open pulled straws (OPS) and grids," Hum. Reprod. 16, 2350 - 2356 (2001).
[PubMed]

M. Terasaki, L. L. Runft, and A. R. Hand, "Changes in organization of the endoplasmic reticulum during Xenopus oocyte maturation and activation," Mol. Biol. Cell 12, 1103-1116 (2001)
[PubMed]

2000 (3)

A. Gabrielsen, P.R. Bhatnager, K. Petersen and S. Lindenberg, "Influence of zona pellucida thickness of human embryos on clinical pregnancy outcome following in vitro fertilization treatment," J. Assist. Reprod. Genet. 17, 323-328 (2000).
[CrossRef] [PubMed]

S.-U. Chen, Y.-L. Lien, and H.-F. Chen, "Open pulled straws for vitrification of mature mouse oocytes preserve patterns of meiotic spindles and chromosomes better than conventional straws," Hum. Reprod. 15, 2598-2603 (2000).
[CrossRef] [PubMed]

S. D. Spandorfer, P. H. Chung, I. Kligman, H. C. Liu, O. K. Davis, and Z. Rosenwal, "An analysis of the effect of age on implantation rates," J. Assist. Reprod. Genet. 17, 303-306 (2000).
[CrossRef] [PubMed]

1999 (1)

J. M. Squirell, D. L. Wokosin, J. G. White, and B. D. Bavister, "Long-term two-photon fluorescence imaging of mammalian embryos without compromising viability," Nat. Biotechnol. 17, 763-767 (1999).
[CrossRef]

1998 (2)

S. Inoué, and R. Oldenbourg, "Microtubule dynamics in mitotic spindle displayed by polarized light microscopy," Mol. Biol. Cell 9, 1603-1607 (1998).
[PubMed]

J. A. Squier, M. Muller, and G. J. Brakenhoff, and K. R. Wilson, "Third harmonic generation microscopy," Opt. Express 3, 315-324 (1998).
[CrossRef] [PubMed]

1997 (3)

K. Konig, P. T. C. So, W. W. Mantulin, E. Gratton, "Cellular response to near-infrared femtosecond laser pulses in two-photon microscopes," Opt. Lett. 22,135-136 (1997).
[CrossRef] [PubMed]

D. Keefe, P. Tran, C. Pellegrini, and R. Oldenbourg, "Polarized light microscopy and digital image processing identify a multilaminar structure of the hamster zona pellucida," Hum. Reprod. 12, 1250-1252 (1997).
[CrossRef] [PubMed]

Y. Barad, H. Eisenberg, M. Horowitz, and Y. Silberberg, "Nonlinear scanning laser microscopy by third harmonic generation," App. Phy. Lett. 70, 922-924 (1997).
[CrossRef]

1996 (1)

Y. Fujino, K. Ozaki, S. Yamamasu, F. Ito, I. Matsuoka, E. Hayashi, H. Nakamura, S. Ogita, E. Sato, and M. Inoue, "DNA fragmentation of oocytes in aged mice," Hum. Reprod. 11, 1480-1483 (1996).
[PubMed]

1995 (2)

T. Y. F. Tsang, "Optical 3rd-harmonic generation at interfaces," Phys. Rev. A 52, 4116-4125 (1995).
[CrossRef]

L. M. Mehlmann, M. Terasaki, L. A. Jaffe, D. Kline, "Reorganization of the endoplasmic reticulum during meiotic maturation of the mouse oocyte," Dev. Biol. 170, 607-615 (1995).
[CrossRef] [PubMed]

1994 (2)

D. F. Albertini and V. Rider, "Patterns of intercellular connectivity in the mammalian cumulus-oocyte complex," Microsc. Res. Tech. 27, 125-133 (1994).
[CrossRef] [PubMed]

P. M. Motta, S. Makabe, T. Naguro, and S. Correr, "Oocyte follicle cells association during development of human ovarian follicle. A study by high resolution scanning and transmission electron microscopy," Arch. Histol. Cytol. 57, 369-394 (1994).
[CrossRef] [PubMed]

1993 (1)

T.  Tokura, Y.  Noda, Y.  Goto, and T.  Mori, "Sequential observation of mitochondrial distribution in mouse oocytes and embryos," J. Assist. Reprod. Genet. 10, 417-426 (1993).
[CrossRef] [PubMed]

1992 (1)

J. V. Blerkom and G. Henry, "Oocyte dysmorphism and aneuploidy in meiotically mature human oocytes after ovarian stimulation," Hum. Reprod. 7, 379-390 (1992).
[PubMed]

1984 (1)

J. V. Blerkom, M. N. Runner, "Mitochondrial reorganization during resumption of arrested meiosis in the mouse oocyte," Am. J. Anat. 171, 335-355(1984).
[CrossRef] [PubMed]

1980 (2)

D. M. Phillips, R. M. Shalgi, "Surface properties of the zona pellucida," J. Exp. Zool. 213, 1-8 (1980).
[CrossRef] [PubMed]

J. C. Bleil and P. M. Wassarman, "Structure and function for the zona pellucida: identification and characterization of the proteins of the mouse oocyte's zona pellucida," Dev. Biol. 76, 185-202 (1980).
[CrossRef] [PubMed]

Albertini, D. F.

D. F. Albertini and S. L. Barrett, "Oocyte-somatic cell communication," Reproduction 61 (Suppl), 49-54 (2003).
[PubMed]

D. F. Albertini and V. Rider, "Patterns of intercellular connectivity in the mammalian cumulus-oocyte complex," Microsc. Res. Tech. 27, 125-133 (1994).
[CrossRef] [PubMed]

Alexander, S.

J. V. Blerkom, P. Davis, V. Mathwig, and S. Alexander, "Domains of high-polarized and low-polarized mitochondria may occur in mouse and human oocytes and early embryos" Hum. Reprod. 17, 393-406 (2002).
[CrossRef] [PubMed]

Au, J. A. D.

Barad, Y.

Y. Barad, H. Eisenberg, M. Horowitz, and Y. Silberberg, "Nonlinear scanning laser microscopy by third harmonic generation," App. Phy. Lett. 70, 922-924 (1997).
[CrossRef]

Barrett, S. L.

D. F. Albertini and S. L. Barrett, "Oocyte-somatic cell communication," Reproduction 61 (Suppl), 49-54 (2003).
[PubMed]

Barzda, V.

Bavister, B. D.

J. M. Squirell, D. L. Wokosin, J. G. White, and B. D. Bavister, "Long-term two-photon fluorescence imaging of mammalian embryos without compromising viability," Nat. Biotechnol. 17, 763-767 (1999).
[CrossRef]

Beaurepaire, E.

D. Debarre, W. Supatto, A. M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M. C. Schanne-Klein, and E. Beaurepaire, "Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy," Nat. Methods 3, 47-53 (2006).
[CrossRef]

Bergh, T.

J. Holte, L.  Berglund, K.  Milton, C.  Garello, G.  Gennarelli, A.  Revelli, T.  Bergh, "Construction of an evidence-based integrated morphology cleavage embryo score for implantation potential of embryos scored and transferred on day 2 after oocyte retrieval," Hum. Reprod. 22, 548-557 (2007)
[CrossRef]

Berglund, L.

J. Holte, L.  Berglund, K.  Milton, C.  Garello, G.  Gennarelli, A.  Revelli, T.  Bergh, "Construction of an evidence-based integrated morphology cleavage embryo score for implantation potential of embryos scored and transferred on day 2 after oocyte retrieval," Hum. Reprod. 22, 548-557 (2007)
[CrossRef]

Bhatnager, P.R.

A. Gabrielsen, P.R. Bhatnager, K. Petersen and S. Lindenberg, "Influence of zona pellucida thickness of human embryos on clinical pregnancy outcome following in vitro fertilization treatment," J. Assist. Reprod. Genet. 17, 323-328 (2000).
[CrossRef] [PubMed]

Biggs, D.

M. Shribak, J. LaFountain, D. Biggs, and S. Inoué, "Quantitative orientation-independent differential interference contrast (DIC) microscopy coupled with orientation-independent polarization microscopy," Microsc. Microanal. 13, 10-11 (2007).
[PubMed]

Bleil, J. C.

J. C. Bleil and P. M. Wassarman, "Structure and function for the zona pellucida: identification and characterization of the proteins of the mouse oocyte's zona pellucida," Dev. Biol. 76, 185-202 (1980).
[CrossRef] [PubMed]

Blerkom, J. V.

J. V. Blerkom, P. Davis, V. Mathwig, and S. Alexander, "Domains of high-polarized and low-polarized mitochondria may occur in mouse and human oocytes and early embryos" Hum. Reprod. 17, 393-406 (2002).
[CrossRef] [PubMed]

J. V. Blerkom and G. Henry, "Oocyte dysmorphism and aneuploidy in meiotically mature human oocytes after ovarian stimulation," Hum. Reprod. 7, 379-390 (1992).
[PubMed]

J. V. Blerkom, M. N. Runner, "Mitochondrial reorganization during resumption of arrested meiosis in the mouse oocyte," Am. J. Anat. 171, 335-355(1984).
[CrossRef] [PubMed]

Brakenhoff, G. J.

J. A. Squier, M. Muller, and G. J. Brakenhoff, and K. R. Wilson, "Third harmonic generation microscopy," Opt. Express 3, 315-324 (1998).
[CrossRef] [PubMed]

M. Muller, J. Squier, K. R. Wilson, and G. J. Brakenhoff, "3D microscopy of transparent objects using third-harmonic generation," J. Microsc.-Oxford 191, 266-274 (1998).
[CrossRef]

A. C. Millard, D. N. Fittinghoff, P. W. Wiseman, M. Muller, G. J. Brakenhoff, J. A. Squier, and K. R. Wilson, "Three dimensional, third harmonic microscopy of living systems," Biophys. J. 78, 800Plat Part 2 (2000).

Bucci, J. A.

W. T. Garside, J. R. L. D. Mola, J. A. Bucci, R. W. Tureck, S. Heyner, "Sequential analysis of zona thickness during in vitro culture of human zygotes: Correlation with embryo quality, age, and implantation," Mol. Reprod. Dev.47, 99-104 (1997).
[CrossRef] [PubMed]

Campagnola, P. J.

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, and W. A. Mohler, "Three dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissues," Biophys. J. 82, 493-508 (2002).
[CrossRef]

Carroll, J.

G. FitzHarris, P. Marangos, and J. Carroll, "Changes in endoplasmic reticulum structure during mouse oocyte maturation are controlled by the cytoskeleton and cytoplasmic dynein," Dev. Biol. 305, 133-144 (2007).
[CrossRef] [PubMed]

G. Fitzharris, P. Marangos, and J. Carroll, "Cell cycle-dependent regulation of structure of endoplasmic reticulum and inositol 1, 4, 5-trisphosphate-induced Ca2+ release in mouse oocytes and embryos," Mol. Biol. Cell 14, 288-301 (2003).
[CrossRef] [PubMed]

Celliers, P. M.

P. Stoller, K. M. Reiser, P. M. Celliers, and A. M. Rubenchik, "Polarization-modulated second harmonic generation in collagen," Biophys. J. 82, 3330-3342 (2002).
[CrossRef] [PubMed]

Chan, Y.-F.

Chang, L.-J.

S.-U. Chen, T.-H. Lee, Y.-R. Lien, Y.-Y. Tsai, L.-J. Chang, and Y.-S. Yang, "Microsuction of blastocoelic fluid before vitrification increased survival and pregnancy of mouse expanded blastocysts, but pretreatment with the cytoskeletal stabilizer did not increase blastocyst survival," Fertil. Steril. 84, 1156-1162 (2005).
[CrossRef] [PubMed]

Chen, H.-F.

S.-U. Chen, Y.-R. Lien, Y.-Y. Cheng, H.-F. Chen, H.-N. Ho, and Y.-S. Yang, "Vitrification of mouse oocytes using closed pulled straws (CPS) achieves a high survival and preserves good patterns of meiotic spindles, compared with conventional straws, open pulled straws (OPS) and grids," Hum. Reprod. 16, 2350 - 2356 (2001).
[PubMed]

S.-U. Chen, Y.-L. Lien, and H.-F. Chen, "Open pulled straws for vitrification of mature mouse oocytes preserve patterns of meiotic spindles and chromosomes better than conventional straws," Hum. Reprod. 15, 2598-2603 (2000).
[CrossRef] [PubMed]

Chen, I.-H.

S.-W. Chu, I.-H. Chen, T.-M. Liu, C.-K. Sun, S.-P. Lee, B.-L. Lin, P.-C. Cheng, M.-X. Kuo, D.-J. Lin, and H.-L. Liu, "Nonlinear bio-photonic crystal effects revealed with multimodal nonlinear microscopy," J. Microsc.-Oxford 208, 190-200 (2002).
[CrossRef]

Chen, S.-U.

S.-U. Chen, Y.-R. Lien, Y.-Y. Cheng, H.-F. Chen, H.-N. Ho, and Y.-S. Yang, "Vitrification of mouse oocytes using closed pulled straws (CPS) achieves a high survival and preserves good patterns of meiotic spindles, compared with conventional straws, open pulled straws (OPS) and grids," Hum. Reprod. 16, 2350 - 2356 (2001).
[PubMed]

S.-U. Chen, Y.-L. Lien, and H.-F. Chen, "Open pulled straws for vitrification of mature mouse oocytes preserve patterns of meiotic spindles and chromosomes better than conventional straws," Hum. Reprod. 15, 2598-2603 (2000).
[CrossRef] [PubMed]

S.-U. Chen, T.-H. Lee, Y.-R. Lien, Y.-Y. Tsai, L.-J. Chang, and Y.-S. Yang, "Microsuction of blastocoelic fluid before vitrification increased survival and pregnancy of mouse expanded blastocysts, but pretreatment with the cytoskeletal stabilizer did not increase blastocyst survival," Fertil. Steril. 84, 1156-1162 (2005).
[CrossRef] [PubMed]

Chen, S.-Y.

C.-K. Sun, S.-W. Chu, S.-Y. Chen, T.-H. Tsai, T.-M. Liu, C.-Y. Lin, and H.-J. Tsai, "Higher harmonic generation microscopy for developmental biology," J. Struct. Bio. 147, 19-30 (2004).
[CrossRef]

S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of ???(2)/???(3) tensors in submicron-scaled bio-tissues by polarization harmonics optical microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

S.-W. Chu, S.-Y. Chen, T.-H. Tsai, T.-M. Liu, C.-Y. Lin, H.-J. Tsai, and C.-K. Sun, "In vivo developmental biology study using noninvasive multi-harmonic generation microscopy," Opt. Express 11, 3093-3099 (2003).
[CrossRef] [PubMed]

S.-Y. Chen, C.-S. Hsieh, S.-W. Chu, C.-Y. Ko, Y.-C. Chen, H.-J. Tsai, C.-H. Hu, C.-K. Sun, "Noninvasive harmonics optical microscopy for long-term observation of embryonic nervous system development in vivo. "J. Biom. Opt. 11, 054022 1-8 (2006).

Chen, Y.-C.

S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of ???(2)/???(3) tensors in submicron-scaled bio-tissues by polarization harmonics optical microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

S.-Y. Chen, C.-S. Hsieh, S.-W. Chu, C.-Y. Ko, Y.-C. Chen, H.-J. Tsai, C.-H. Hu, C.-K. Sun, "Noninvasive harmonics optical microscopy for long-term observation of embryonic nervous system development in vivo. "J. Biom. Opt. 11, 054022 1-8 (2006).

Cheng, P.-C.

S.-W. Chu, I.-H. Chen, T.-M. Liu, C.-K. Sun, S.-P. Lee, B.-L. Lin, P.-C. Cheng, M.-X. Kuo, D.-J. Lin, and H.-L. Liu, "Nonlinear bio-photonic crystal effects revealed with multimodal nonlinear microscopy," J. Microsc.-Oxford 208, 190-200 (2002).
[CrossRef]

Cheng, Y.-Y.

S.-U. Chen, Y.-R. Lien, Y.-Y. Cheng, H.-F. Chen, H.-N. Ho, and Y.-S. Yang, "Vitrification of mouse oocytes using closed pulled straws (CPS) achieves a high survival and preserves good patterns of meiotic spindles, compared with conventional straws, open pulled straws (OPS) and grids," Hum. Reprod. 16, 2350 - 2356 (2001).
[PubMed]

Chern, G.-W.

S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of ???(2)/???(3) tensors in submicron-scaled bio-tissues by polarization harmonics optical microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

Chu, S.-W.

S.-W. Chu, S.-P. Tai, C.-L. Ho, C.-H. Lin, and C.-K Sun, "High-resolution simultaneous three-photon fluorescence and third-harmonic-generation microscopy," Microsc. Res. Tech. 66, 193-197 (2005).
[CrossRef] [PubMed]

S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of ???(2)/???(3) tensors in submicron-scaled bio-tissues by polarization harmonics optical microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

C.-K. Sun, S.-W. Chu, S.-Y. Chen, T.-H. Tsai, T.-M. Liu, C.-Y. Lin, and H.-J. Tsai, "Higher harmonic generation microscopy for developmental biology," J. Struct. Bio. 147, 19-30 (2004).
[CrossRef]

S.-W. Chu, S.-Y. Chen, T.-H. Tsai, T.-M. Liu, C.-Y. Lin, H.-J. Tsai, and C.-K. Sun, "In vivo developmental biology study using noninvasive multi-harmonic generation microscopy," Opt. Express 11, 3093-3099 (2003).
[CrossRef] [PubMed]

S.-W. Chu, I.-H. Chen, T.-M. Liu, C.-K. Sun, S.-P. Lee, B.-L. Lin, P.-C. Cheng, M.-X. Kuo, D.-J. Lin, and H.-L. Liu, "Nonlinear bio-photonic crystal effects revealed with multimodal nonlinear microscopy," J. Microsc.-Oxford 208, 190-200 (2002).
[CrossRef]

S.-Y. Chen, C.-S. Hsieh, S.-W. Chu, C.-Y. Ko, Y.-C. Chen, H.-J. Tsai, C.-H. Hu, C.-K. Sun, "Noninvasive harmonics optical microscopy for long-term observation of embryonic nervous system development in vivo. "J. Biom. Opt. 11, 054022 1-8 (2006).

Chung, P. H.

S. D. Spandorfer, P. H. Chung, I. Kligman, H. C. Liu, O. K. Davis, and Z. Rosenwal, "An analysis of the effect of age on implantation rates," J. Assist. Reprod. Genet. 17, 303-306 (2000).
[CrossRef] [PubMed]

Combettes, L.

D. Debarre, W. Supatto, A. M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M. C. Schanne-Klein, and E. Beaurepaire, "Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy," Nat. Methods 3, 47-53 (2006).
[CrossRef]

Cooke, S.

S. Cooke, J. P. P. Tyler, G. L. Driscoll, "Meiotic spindle location and identification and its effect on embryonic cleavage plane and early development," Hum. Reprod. 18,2397-2405 (2003)
[CrossRef] [PubMed]

Correr, S.

P. M. Motta, S. Makabe, T. Naguro, and S. Correr, "Oocyte follicle cells association during development of human ovarian follicle. A study by high resolution scanning and transmission electron microscopy," Arch. Histol. Cytol. 57, 369-394 (1994).
[CrossRef] [PubMed]

Davis, O. K.

S. D. Spandorfer, P. H. Chung, I. Kligman, H. C. Liu, O. K. Davis, and Z. Rosenwal, "An analysis of the effect of age on implantation rates," J. Assist. Reprod. Genet. 17, 303-306 (2000).
[CrossRef] [PubMed]

Davis, P.

J. V. Blerkom, P. Davis, V. Mathwig, and S. Alexander, "Domains of high-polarized and low-polarized mitochondria may occur in mouse and human oocytes and early embryos" Hum. Reprod. 17, 393-406 (2002).
[CrossRef] [PubMed]

de Bruin, J. P.

J. P. de Bruin, M. Dorland, E. R. Spek, G. Posthuma, M. van Haaften, C. W. Looman, and E. R. te Velde, "Age-related changes in the ultrastructure of the resting follicle pool in human ovaries," Biol. Reprod. 70, 419-424 (2004).
[CrossRef]

Debarre, D.

D. Debarre, W. Supatto, A. M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M. C. Schanne-Klein, and E. Beaurepaire, "Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy," Nat. Methods 3, 47-53 (2006).
[CrossRef]

Dorland, M.

J. P. de Bruin, M. Dorland, E. R. Spek, G. Posthuma, M. van Haaften, C. W. Looman, and E. R. te Velde, "Age-related changes in the ultrastructure of the resting follicle pool in human ovaries," Biol. Reprod. 70, 419-424 (2004).
[CrossRef]

Driscoll, G. L.

S. Cooke, J. P. P. Tyler, G. L. Driscoll, "Meiotic spindle location and identification and its effect on embryonic cleavage plane and early development," Hum. Reprod. 18,2397-2405 (2003)
[CrossRef] [PubMed]

Eichenlaub-Ritter, U.

Y. Shen, T. Stalf, C. Mehnert, U. Eichenlaub-Ritter, and H.-R. Tinneberg, "High magnitude of light retardation by the zona pellucida is associated with conception cycles," Hum. Reprod. 20, 1596-1606 (2005).
[CrossRef] [PubMed]

Eisenberg, H.

Y. Barad, H. Eisenberg, M. Horowitz, and Y. Silberberg, "Nonlinear scanning laser microscopy by third harmonic generation," App. Phy. Lett. 70, 922-924 (1997).
[CrossRef]

Elmore, S.

Fabre, A.

D. Debarre, W. Supatto, A. M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M. C. Schanne-Klein, and E. Beaurepaire, "Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy," Nat. Methods 3, 47-53 (2006).
[CrossRef]

Fittinghoff, D. N.

A. C. Millard, D. N. Fittinghoff, P. W. Wiseman, M. Muller, G. J. Brakenhoff, J. A. Squier, and K. R. Wilson, "Three dimensional, third harmonic microscopy of living systems," Biophys. J. 78, 800Plat Part 2 (2000).

FitzHarris, G.

G. FitzHarris, P. Marangos, and J. Carroll, "Changes in endoplasmic reticulum structure during mouse oocyte maturation are controlled by the cytoskeleton and cytoplasmic dynein," Dev. Biol. 305, 133-144 (2007).
[CrossRef] [PubMed]

G. Fitzharris, P. Marangos, and J. Carroll, "Cell cycle-dependent regulation of structure of endoplasmic reticulum and inositol 1, 4, 5-trisphosphate-induced Ca2+ release in mouse oocytes and embryos," Mol. Biol. Cell 14, 288-301 (2003).
[CrossRef] [PubMed]

Fujino, Y.

Y. Fujino, K. Ozaki, S. Yamamasu, F. Ito, I. Matsuoka, E. Hayashi, H. Nakamura, S. Ogita, E. Sato, and M. Inoue, "DNA fragmentation of oocytes in aged mice," Hum. Reprod. 11, 1480-1483 (1996).
[PubMed]

Gabrielsen, A.

A. Gabrielsen, P.R. Bhatnager, K. Petersen and S. Lindenberg, "Influence of zona pellucida thickness of human embryos on clinical pregnancy outcome following in vitro fertilization treatment," J. Assist. Reprod. Genet. 17, 323-328 (2000).
[CrossRef] [PubMed]

Garello, C.

J. Holte, L.  Berglund, K.  Milton, C.  Garello, G.  Gennarelli, A.  Revelli, T.  Bergh, "Construction of an evidence-based integrated morphology cleavage embryo score for implantation potential of embryos scored and transferred on day 2 after oocyte retrieval," Hum. Reprod. 22, 548-557 (2007)
[CrossRef]

Garside, W. T.

W. T. Garside, J. R. L. D. Mola, J. A. Bucci, R. W. Tureck, S. Heyner, "Sequential analysis of zona thickness during in vitro culture of human zygotes: Correlation with embryo quality, age, and implantation," Mol. Reprod. Dev.47, 99-104 (1997).
[CrossRef] [PubMed]

Gennarelli, G.

J. Holte, L.  Berglund, K.  Milton, C.  Garello, G.  Gennarelli, A.  Revelli, T.  Bergh, "Construction of an evidence-based integrated morphology cleavage embryo score for implantation potential of embryos scored and transferred on day 2 after oocyte retrieval," Hum. Reprod. 22, 548-557 (2007)
[CrossRef]

Goto, Y.

T.  Tokura, Y.  Noda, Y.  Goto, and T.  Mori, "Sequential observation of mitochondrial distribution in mouse oocytes and embryos," J. Assist. Reprod. Genet. 10, 417-426 (1993).
[CrossRef] [PubMed]

Gratton, E.

Greenhalgh, C.

Hand, A. R.

M. Terasaki, L. L. Runft, and A. R. Hand, "Changes in organization of the endoplasmic reticulum during Xenopus oocyte maturation and activation," Mol. Biol. Cell 12, 1103-1116 (2001)
[PubMed]

Hayashi, E.

Y. Fujino, K. Ozaki, S. Yamamasu, F. Ito, I. Matsuoka, E. Hayashi, H. Nakamura, S. Ogita, E. Sato, and M. Inoue, "DNA fragmentation of oocytes in aged mice," Hum. Reprod. 11, 1480-1483 (1996).
[PubMed]

Henry, G.

J. V. Blerkom and G. Henry, "Oocyte dysmorphism and aneuploidy in meiotically mature human oocytes after ovarian stimulation," Hum. Reprod. 7, 379-390 (1992).
[PubMed]

Heyner, S.

W. T. Garside, J. R. L. D. Mola, J. A. Bucci, R. W. Tureck, S. Heyner, "Sequential analysis of zona thickness during in vitro culture of human zygotes: Correlation with embryo quality, age, and implantation," Mol. Reprod. Dev.47, 99-104 (1997).
[CrossRef] [PubMed]

Ho, C.-L.

S.-W. Chu, S.-P. Tai, C.-L. Ho, C.-H. Lin, and C.-K Sun, "High-resolution simultaneous three-photon fluorescence and third-harmonic-generation microscopy," Microsc. Res. Tech. 66, 193-197 (2005).
[CrossRef] [PubMed]

Ho, H.-N.

S.-U. Chen, Y.-R. Lien, Y.-Y. Cheng, H.-F. Chen, H.-N. Ho, and Y.-S. Yang, "Vitrification of mouse oocytes using closed pulled straws (CPS) achieves a high survival and preserves good patterns of meiotic spindles, compared with conventional straws, open pulled straws (OPS) and grids," Hum. Reprod. 16, 2350 - 2356 (2001).
[PubMed]

Holte, J.

J. Holte, L.  Berglund, K.  Milton, C.  Garello, G.  Gennarelli, A.  Revelli, T.  Bergh, "Construction of an evidence-based integrated morphology cleavage embryo score for implantation potential of embryos scored and transferred on day 2 after oocyte retrieval," Hum. Reprod. 22, 548-557 (2007)
[CrossRef]

Hoppe, P. E.

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, and W. A. Mohler, "Three dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissues," Biophys. J. 82, 493-508 (2002).
[CrossRef]

Horowitz, M.

Y. Barad, H. Eisenberg, M. Horowitz, and Y. Silberberg, "Nonlinear scanning laser microscopy by third harmonic generation," App. Phy. Lett. 70, 922-924 (1997).
[CrossRef]

Hsieh, C.-S.

S.-Y. Chen, C.-S. Hsieh, S.-W. Chu, C.-Y. Ko, Y.-C. Chen, H.-J. Tsai, C.-H. Hu, C.-K. Sun, "Noninvasive harmonics optical microscopy for long-term observation of embryonic nervous system development in vivo. "J. Biom. Opt. 11, 054022 1-8 (2006).

Hu, C.-H.

S.-Y. Chen, C.-S. Hsieh, S.-W. Chu, C.-Y. Ko, Y.-C. Chen, H.-J. Tsai, C.-H. Hu, C.-K. Sun, "Noninvasive harmonics optical microscopy for long-term observation of embryonic nervous system development in vivo. "J. Biom. Opt. 11, 054022 1-8 (2006).

Huang, H.-J.

Inoue, M.

Y. Fujino, K. Ozaki, S. Yamamasu, F. Ito, I. Matsuoka, E. Hayashi, H. Nakamura, S. Ogita, E. Sato, and M. Inoue, "DNA fragmentation of oocytes in aged mice," Hum. Reprod. 11, 1480-1483 (1996).
[PubMed]

Inoué, S.

M. Shribak, J. LaFountain, D. Biggs, and S. Inoué, "Quantitative orientation-independent differential interference contrast (DIC) microscopy coupled with orientation-independent polarization microscopy," Microsc. Microanal. 13, 10-11 (2007).
[PubMed]

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L. M. Mehlmann, M. Terasaki, L. A. Jaffe, D. Kline, "Reorganization of the endoplasmic reticulum during meiotic maturation of the mouse oocyte," Dev. Biol. 170, 607-615 (1995).
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D. Keefe, P. Tran, C. Pellegrini, and R. Oldenbourg, "Polarized light microscopy and digital image processing identify a multilaminar structure of the hamster zona pellucida," Hum. Reprod. 12, 1250-1252 (1997).
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C. Pelletier, D. L. Keefe, and J. R. Trimarchi, "Noninvasive polarized light microscopy quantitatively distinguishes the multilaminar structure of the zona pellucida of living human eggs and embryos," Fertil. Steril. 81, 850-856 (2004).
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S. D. Spandorfer, P. H. Chung, I. Kligman, H. C. Liu, O. K. Davis, and Z. Rosenwal, "An analysis of the effect of age on implantation rates," J. Assist. Reprod. Genet. 17, 303-306 (2000).
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L. M. Mehlmann, M. Terasaki, L. A. Jaffe, D. Kline, "Reorganization of the endoplasmic reticulum during meiotic maturation of the mouse oocyte," Dev. Biol. 170, 607-615 (1995).
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Kubo, H.

J. Otsuki, A. Okada, K. Morimoto, Y. Nagai, and H. Kubo, "The relationship between pregnancy outcome and smooth endoplasmic reticulum clusters in MII human oocytes," Hum. Reprod. 19, 1591-1597 (2004).
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Kuo, M.-X.

S.-W. Chu, I.-H. Chen, T.-M. Liu, C.-K. Sun, S.-P. Lee, B.-L. Lin, P.-C. Cheng, M.-X. Kuo, D.-J. Lin, and H.-L. Liu, "Nonlinear bio-photonic crystal effects revealed with multimodal nonlinear microscopy," J. Microsc.-Oxford 208, 190-200 (2002).
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M. Shribak, J. LaFountain, D. Biggs, and S. Inoué, "Quantitative orientation-independent differential interference contrast (DIC) microscopy coupled with orientation-independent polarization microscopy," Microsc. Microanal. 13, 10-11 (2007).
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S.-W. Chu, I.-H. Chen, T.-M. Liu, C.-K. Sun, S.-P. Lee, B.-L. Lin, P.-C. Cheng, M.-X. Kuo, D.-J. Lin, and H.-L. Liu, "Nonlinear bio-photonic crystal effects revealed with multimodal nonlinear microscopy," J. Microsc.-Oxford 208, 190-200 (2002).
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S.-U. Chen, T.-H. Lee, Y.-R. Lien, Y.-Y. Tsai, L.-J. Chang, and Y.-S. Yang, "Microsuction of blastocoelic fluid before vitrification increased survival and pregnancy of mouse expanded blastocysts, but pretreatment with the cytoskeletal stabilizer did not increase blastocyst survival," Fertil. Steril. 84, 1156-1162 (2005).
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S.-U. Chen, Y.-L. Lien, and H.-F. Chen, "Open pulled straws for vitrification of mature mouse oocytes preserve patterns of meiotic spindles and chromosomes better than conventional straws," Hum. Reprod. 15, 2598-2603 (2000).
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S.-U. Chen, Y.-R. Lien, Y.-Y. Cheng, H.-F. Chen, H.-N. Ho, and Y.-S. Yang, "Vitrification of mouse oocytes using closed pulled straws (CPS) achieves a high survival and preserves good patterns of meiotic spindles, compared with conventional straws, open pulled straws (OPS) and grids," Hum. Reprod. 16, 2350 - 2356 (2001).
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S.-U. Chen, T.-H. Lee, Y.-R. Lien, Y.-Y. Tsai, L.-J. Chang, and Y.-S. Yang, "Microsuction of blastocoelic fluid before vitrification increased survival and pregnancy of mouse expanded blastocysts, but pretreatment with the cytoskeletal stabilizer did not increase blastocyst survival," Fertil. Steril. 84, 1156-1162 (2005).
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S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of ???(2)/???(3) tensors in submicron-scaled bio-tissues by polarization harmonics optical microscopy," Biophys. J. 86, 3914-3922 (2004).
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S.-W. Chu, S.-P. Tai, C.-L. Ho, C.-H. Lin, and C.-K Sun, "High-resolution simultaneous three-photon fluorescence and third-harmonic-generation microscopy," Microsc. Res. Tech. 66, 193-197 (2005).
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C.-K. Sun, S.-W. Chu, S.-Y. Chen, T.-H. Tsai, T.-M. Liu, C.-Y. Lin, and H.-J. Tsai, "Higher harmonic generation microscopy for developmental biology," J. Struct. Bio. 147, 19-30 (2004).
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S.-W. Chu, I.-H. Chen, T.-M. Liu, C.-K. Sun, S.-P. Lee, B.-L. Lin, P.-C. Cheng, M.-X. Kuo, D.-J. Lin, and H.-L. Liu, "Nonlinear bio-photonic crystal effects revealed with multimodal nonlinear microscopy," J. Microsc.-Oxford 208, 190-200 (2002).
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A. Gabrielsen, P.R. Bhatnager, K. Petersen and S. Lindenberg, "Influence of zona pellucida thickness of human embryos on clinical pregnancy outcome following in vitro fertilization treatment," J. Assist. Reprod. Genet. 17, 323-328 (2000).
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S. D. Spandorfer, P. H. Chung, I. Kligman, H. C. Liu, O. K. Davis, and Z. Rosenwal, "An analysis of the effect of age on implantation rates," J. Assist. Reprod. Genet. 17, 303-306 (2000).
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C.-H. Yu, S.-P. Tai, C.-T. Kung, W.-J. Lee, Y.-F. Chan, H.-L. Liu, J.-Y. Lyu, C.-K. Sun, "Molecular third-harmonic-generation microscopy through resonance enhancement with absorbing dye," Opt. Lett. 33,387-389 (2008).
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L. Liu and D. L. Keefe, "Ageing-associated aberration in meiosis of oocytes from senescence-accelerated mice," Hum. Reprod. 17, 2678-2685 (2002).
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C.-K. Sun, S.-W. Chu, S.-Y. Chen, T.-H. Tsai, T.-M. Liu, C.-Y. Lin, and H.-J. Tsai, "Higher harmonic generation microscopy for developmental biology," J. Struct. Bio. 147, 19-30 (2004).
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S.-W. Chu, I.-H. Chen, T.-M. Liu, C.-K. Sun, S.-P. Lee, B.-L. Lin, P.-C. Cheng, M.-X. Kuo, D.-J. Lin, and H.-L. Liu, "Nonlinear bio-photonic crystal effects revealed with multimodal nonlinear microscopy," J. Microsc.-Oxford 208, 190-200 (2002).
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J. P. de Bruin, M. Dorland, E. R. Spek, G. Posthuma, M. van Haaften, C. W. Looman, and E. R. te Velde, "Age-related changes in the ultrastructure of the resting follicle pool in human ovaries," Biol. Reprod. 70, 419-424 (2004).
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P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, and W. A. Mohler, "Three dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissues," Biophys. J. 82, 493-508 (2002).
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J. V. Blerkom, P. Davis, V. Mathwig, and S. Alexander, "Domains of high-polarized and low-polarized mitochondria may occur in mouse and human oocytes and early embryos" Hum. Reprod. 17, 393-406 (2002).
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Y. Fujino, K. Ozaki, S. Yamamasu, F. Ito, I. Matsuoka, E. Hayashi, H. Nakamura, S. Ogita, E. Sato, and M. Inoue, "DNA fragmentation of oocytes in aged mice," Hum. Reprod. 11, 1480-1483 (1996).
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L. M. Mehlmann, M. Terasaki, L. A. Jaffe, D. Kline, "Reorganization of the endoplasmic reticulum during meiotic maturation of the mouse oocyte," Dev. Biol. 170, 607-615 (1995).
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Mehnert, C.

Y. Shen, T. Stalf, C. Mehnert, U. Eichenlaub-Ritter, and H.-R. Tinneberg, "High magnitude of light retardation by the zona pellucida is associated with conception cycles," Hum. Reprod. 20, 1596-1606 (2005).
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P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, and W. A. Mohler, "Three dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissues," Biophys. J. 82, 493-508 (2002).
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A. C. Millard, D. N. Fittinghoff, P. W. Wiseman, M. Muller, G. J. Brakenhoff, J. A. Squier, and K. R. Wilson, "Three dimensional, third harmonic microscopy of living systems," Biophys. J. 78, 800Plat Part 2 (2000).

Milton, K.

J. Holte, L.  Berglund, K.  Milton, C.  Garello, G.  Gennarelli, A.  Revelli, T.  Bergh, "Construction of an evidence-based integrated morphology cleavage embryo score for implantation potential of embryos scored and transferred on day 2 after oocyte retrieval," Hum. Reprod. 22, 548-557 (2007)
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Mohler, W. A.

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, and W. A. Mohler, "Three dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissues," Biophys. J. 82, 493-508 (2002).
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R. D. Moreno, G. Schatten, and J. Ramalho-Santos, "Golgi apparatus dynamics during mouse oocyte in vitro maturation: effect of the membrane trafficking inhibitor brefeldin A," Biol. Reprod. 66, 1259-1266 (2002)
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T.  Tokura, Y.  Noda, Y.  Goto, and T.  Mori, "Sequential observation of mitochondrial distribution in mouse oocytes and embryos," J. Assist. Reprod. Genet. 10, 417-426 (1993).
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J. Otsuki, A. Okada, K. Morimoto, Y. Nagai, and H. Kubo, "The relationship between pregnancy outcome and smooth endoplasmic reticulum clusters in MII human oocytes," Hum. Reprod. 19, 1591-1597 (2004).
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Motta, P. M.

P. M. Motta, S. Makabe, T. Naguro, and S. Correr, "Oocyte follicle cells association during development of human ovarian follicle. A study by high resolution scanning and transmission electron microscopy," Arch. Histol. Cytol. 57, 369-394 (1994).
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Muller, M.

J. A. Squier, M. Muller, and G. J. Brakenhoff, and K. R. Wilson, "Third harmonic generation microscopy," Opt. Express 3, 315-324 (1998).
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A. C. Millard, D. N. Fittinghoff, P. W. Wiseman, M. Muller, G. J. Brakenhoff, J. A. Squier, and K. R. Wilson, "Three dimensional, third harmonic microscopy of living systems," Biophys. J. 78, 800Plat Part 2 (2000).

M. Muller, J. Squier, K. R. Wilson, and G. J. Brakenhoff, "3D microscopy of transparent objects using third-harmonic generation," J. Microsc.-Oxford 191, 266-274 (1998).
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J. Otsuki, A. Okada, K. Morimoto, Y. Nagai, and H. Kubo, "The relationship between pregnancy outcome and smooth endoplasmic reticulum clusters in MII human oocytes," Hum. Reprod. 19, 1591-1597 (2004).
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Naguro, T.

P. M. Motta, S. Makabe, T. Naguro, and S. Correr, "Oocyte follicle cells association during development of human ovarian follicle. A study by high resolution scanning and transmission electron microscopy," Arch. Histol. Cytol. 57, 369-394 (1994).
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Nakamura, H.

Y. Fujino, K. Ozaki, S. Yamamasu, F. Ito, I. Matsuoka, E. Hayashi, H. Nakamura, S. Ogita, E. Sato, and M. Inoue, "DNA fragmentation of oocytes in aged mice," Hum. Reprod. 11, 1480-1483 (1996).
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T.  Tokura, Y.  Noda, Y.  Goto, and T.  Mori, "Sequential observation of mitochondrial distribution in mouse oocytes and embryos," J. Assist. Reprod. Genet. 10, 417-426 (1993).
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Y. Fujino, K. Ozaki, S. Yamamasu, F. Ito, I. Matsuoka, E. Hayashi, H. Nakamura, S. Ogita, E. Sato, and M. Inoue, "DNA fragmentation of oocytes in aged mice," Hum. Reprod. 11, 1480-1483 (1996).
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J. Otsuki, A. Okada, K. Morimoto, Y. Nagai, and H. Kubo, "The relationship between pregnancy outcome and smooth endoplasmic reticulum clusters in MII human oocytes," Hum. Reprod. 19, 1591-1597 (2004).
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Oldenbourg, R.

S. Inoué, and R. Oldenbourg, "Microtubule dynamics in mitotic spindle displayed by polarized light microscopy," Mol. Biol. Cell 9, 1603-1607 (1998).
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D. Keefe, P. Tran, C. Pellegrini, and R. Oldenbourg, "Polarized light microscopy and digital image processing identify a multilaminar structure of the hamster zona pellucida," Hum. Reprod. 12, 1250-1252 (1997).
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J. Otsuki, A. Okada, K. Morimoto, Y. Nagai, and H. Kubo, "The relationship between pregnancy outcome and smooth endoplasmic reticulum clusters in MII human oocytes," Hum. Reprod. 19, 1591-1597 (2004).
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Y. Fujino, K. Ozaki, S. Yamamasu, F. Ito, I. Matsuoka, E. Hayashi, H. Nakamura, S. Ogita, E. Sato, and M. Inoue, "DNA fragmentation of oocytes in aged mice," Hum. Reprod. 11, 1480-1483 (1996).
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Pellegrini, C.

D. Keefe, P. Tran, C. Pellegrini, and R. Oldenbourg, "Polarized light microscopy and digital image processing identify a multilaminar structure of the hamster zona pellucida," Hum. Reprod. 12, 1250-1252 (1997).
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Pelletier, C.

C. Pelletier, D. L. Keefe, and J. R. Trimarchi, "Noninvasive polarized light microscopy quantitatively distinguishes the multilaminar structure of the zona pellucida of living human eggs and embryos," Fertil. Steril. 81, 850-856 (2004).
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D. Debarre, W. Supatto, A. M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M. C. Schanne-Klein, and E. Beaurepaire, "Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy," Nat. Methods 3, 47-53 (2006).
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Petersen, K.

A. Gabrielsen, P.R. Bhatnager, K. Petersen and S. Lindenberg, "Influence of zona pellucida thickness of human embryos on clinical pregnancy outcome following in vitro fertilization treatment," J. Assist. Reprod. Genet. 17, 323-328 (2000).
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D. M. Phillips, R. M. Shalgi, "Surface properties of the zona pellucida," J. Exp. Zool. 213, 1-8 (1980).
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Posthuma, G.

J. P. de Bruin, M. Dorland, E. R. Spek, G. Posthuma, M. van Haaften, C. W. Looman, and E. R. te Velde, "Age-related changes in the ultrastructure of the resting follicle pool in human ovaries," Biol. Reprod. 70, 419-424 (2004).
[CrossRef]

Ramalho-Santos, J.

R. D. Moreno, G. Schatten, and J. Ramalho-Santos, "Golgi apparatus dynamics during mouse oocyte in vitro maturation: effect of the membrane trafficking inhibitor brefeldin A," Biol. Reprod. 66, 1259-1266 (2002)
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P. Stoller, K. M. Reiser, P. M. Celliers, and A. M. Rubenchik, "Polarization-modulated second harmonic generation in collagen," Biophys. J. 82, 3330-3342 (2002).
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Revelli, A.

J. Holte, L.  Berglund, K.  Milton, C.  Garello, G.  Gennarelli, A.  Revelli, T.  Bergh, "Construction of an evidence-based integrated morphology cleavage embryo score for implantation potential of embryos scored and transferred on day 2 after oocyte retrieval," Hum. Reprod. 22, 548-557 (2007)
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Rosenwal, Z.

S. D. Spandorfer, P. H. Chung, I. Kligman, H. C. Liu, O. K. Davis, and Z. Rosenwal, "An analysis of the effect of age on implantation rates," J. Assist. Reprod. Genet. 17, 303-306 (2000).
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Rubenchik, A. M.

P. Stoller, K. M. Reiser, P. M. Celliers, and A. M. Rubenchik, "Polarization-modulated second harmonic generation in collagen," Biophys. J. 82, 3330-3342 (2002).
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M. Terasaki, L. L. Runft, and A. R. Hand, "Changes in organization of the endoplasmic reticulum during Xenopus oocyte maturation and activation," Mol. Biol. Cell 12, 1103-1116 (2001)
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J. V. Blerkom, M. N. Runner, "Mitochondrial reorganization during resumption of arrested meiosis in the mouse oocyte," Am. J. Anat. 171, 335-355(1984).
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Sato, E.

Y. Fujino, K. Ozaki, S. Yamamasu, F. Ito, I. Matsuoka, E. Hayashi, H. Nakamura, S. Ogita, E. Sato, and M. Inoue, "DNA fragmentation of oocytes in aged mice," Hum. Reprod. 11, 1480-1483 (1996).
[PubMed]

Schanne-Klein, M. C.

D. Debarre, W. Supatto, A. M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M. C. Schanne-Klein, and E. Beaurepaire, "Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy," Nat. Methods 3, 47-53 (2006).
[CrossRef]

Schatten, G.

R. D. Moreno, G. Schatten, and J. Ramalho-Santos, "Golgi apparatus dynamics during mouse oocyte in vitro maturation: effect of the membrane trafficking inhibitor brefeldin A," Biol. Reprod. 66, 1259-1266 (2002)
[CrossRef] [PubMed]

Shalgi, R. M.

D. M. Phillips, R. M. Shalgi, "Surface properties of the zona pellucida," J. Exp. Zool. 213, 1-8 (1980).
[CrossRef] [PubMed]

Shen, Y.

Y. Shen, T. Stalf, C. Mehnert, U. Eichenlaub-Ritter, and H.-R. Tinneberg, "High magnitude of light retardation by the zona pellucida is associated with conception cycles," Hum. Reprod. 20, 1596-1606 (2005).
[CrossRef] [PubMed]

Shribak, M.

M. Shribak, J. LaFountain, D. Biggs, and S. Inoué, "Quantitative orientation-independent differential interference contrast (DIC) microscopy coupled with orientation-independent polarization microscopy," Microsc. Microanal. 13, 10-11 (2007).
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Y. Barad, H. Eisenberg, M. Horowitz, and Y. Silberberg, "Nonlinear scanning laser microscopy by third harmonic generation," App. Phy. Lett. 70, 922-924 (1997).
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Spandorfer, S. D.

S. D. Spandorfer, P. H. Chung, I. Kligman, H. C. Liu, O. K. Davis, and Z. Rosenwal, "An analysis of the effect of age on implantation rates," J. Assist. Reprod. Genet. 17, 303-306 (2000).
[CrossRef] [PubMed]

Spek, E. R.

J. P. de Bruin, M. Dorland, E. R. Spek, G. Posthuma, M. van Haaften, C. W. Looman, and E. R. te Velde, "Age-related changes in the ultrastructure of the resting follicle pool in human ovaries," Biol. Reprod. 70, 419-424 (2004).
[CrossRef]

Squier, J.

Squier, J. A.

J. A. Squier, M. Muller, and G. J. Brakenhoff, and K. R. Wilson, "Third harmonic generation microscopy," Opt. Express 3, 315-324 (1998).
[CrossRef] [PubMed]

A. C. Millard, D. N. Fittinghoff, P. W. Wiseman, M. Muller, G. J. Brakenhoff, J. A. Squier, and K. R. Wilson, "Three dimensional, third harmonic microscopy of living systems," Biophys. J. 78, 800Plat Part 2 (2000).

Squirell, J. M.

J. M. Squirell, D. L. Wokosin, J. G. White, and B. D. Bavister, "Long-term two-photon fluorescence imaging of mammalian embryos without compromising viability," Nat. Biotechnol. 17, 763-767 (1999).
[CrossRef]

Stalf, T.

Y. Shen, T. Stalf, C. Mehnert, U. Eichenlaub-Ritter, and H.-R. Tinneberg, "High magnitude of light retardation by the zona pellucida is associated with conception cycles," Hum. Reprod. 20, 1596-1606 (2005).
[CrossRef] [PubMed]

Stoller, P.

P. Stoller, K. M. Reiser, P. M. Celliers, and A. M. Rubenchik, "Polarization-modulated second harmonic generation in collagen," Biophys. J. 82, 3330-3342 (2002).
[CrossRef] [PubMed]

Sun, C.-K

S.-W. Chu, S.-P. Tai, C.-L. Ho, C.-H. Lin, and C.-K Sun, "High-resolution simultaneous three-photon fluorescence and third-harmonic-generation microscopy," Microsc. Res. Tech. 66, 193-197 (2005).
[CrossRef] [PubMed]

Sun, C.-K.

C.-H. Yu, S.-P. Tai, C.-T. Kung, W.-J. Lee, Y.-F. Chan, H.-L. Liu, J.-Y. Lyu, C.-K. Sun, "Molecular third-harmonic-generation microscopy through resonance enhancement with absorbing dye," Opt. Lett. 33,387-389 (2008).
[CrossRef] [PubMed]

C.-H. Yu, S.-P. Tai, C.-T. Kung, I.-J. Wang, H.-C. Yu, H.-J. Huang, W.-J. Lee, Y.-F. Chan, and C.-K. Sun, "In vivo and ex vivo imaging of intra-tissue elastic fibers using third-harmonic-generation microscopy," Opt. Express 15, 11167-11177 (2007).
[CrossRef] [PubMed]

S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of ???(2)/???(3) tensors in submicron-scaled bio-tissues by polarization harmonics optical microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

C.-K. Sun, S.-W. Chu, S.-Y. Chen, T.-H. Tsai, T.-M. Liu, C.-Y. Lin, and H.-J. Tsai, "Higher harmonic generation microscopy for developmental biology," J. Struct. Bio. 147, 19-30 (2004).
[CrossRef]

S.-W. Chu, S.-Y. Chen, T.-H. Tsai, T.-M. Liu, C.-Y. Lin, H.-J. Tsai, and C.-K. Sun, "In vivo developmental biology study using noninvasive multi-harmonic generation microscopy," Opt. Express 11, 3093-3099 (2003).
[CrossRef] [PubMed]

S.-W. Chu, I.-H. Chen, T.-M. Liu, C.-K. Sun, S.-P. Lee, B.-L. Lin, P.-C. Cheng, M.-X. Kuo, D.-J. Lin, and H.-L. Liu, "Nonlinear bio-photonic crystal effects revealed with multimodal nonlinear microscopy," J. Microsc.-Oxford 208, 190-200 (2002).
[CrossRef]

S.-Y. Chen, C.-S. Hsieh, S.-W. Chu, C.-Y. Ko, Y.-C. Chen, H.-J. Tsai, C.-H. Hu, C.-K. Sun, "Noninvasive harmonics optical microscopy for long-term observation of embryonic nervous system development in vivo. "J. Biom. Opt. 11, 054022 1-8 (2006).

Supatto, W.

D. Debarre, W. Supatto, A. M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M. C. Schanne-Klein, and E. Beaurepaire, "Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy," Nat. Methods 3, 47-53 (2006).
[CrossRef]

Tai, S.-P.

te Velde, E. R.

J. P. de Bruin, M. Dorland, E. R. Spek, G. Posthuma, M. van Haaften, C. W. Looman, and E. R. te Velde, "Age-related changes in the ultrastructure of the resting follicle pool in human ovaries," Biol. Reprod. 70, 419-424 (2004).
[CrossRef]

Terasaki, M.

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, and W. A. Mohler, "Three dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissues," Biophys. J. 82, 493-508 (2002).
[CrossRef]

M. Terasaki, L. L. Runft, and A. R. Hand, "Changes in organization of the endoplasmic reticulum during Xenopus oocyte maturation and activation," Mol. Biol. Cell 12, 1103-1116 (2001)
[PubMed]

L. M. Mehlmann, M. Terasaki, L. A. Jaffe, D. Kline, "Reorganization of the endoplasmic reticulum during meiotic maturation of the mouse oocyte," Dev. Biol. 170, 607-615 (1995).
[CrossRef] [PubMed]

Thouas, G. A.

G. A. Thouas, A. O. Trounson, and G. M. Jones, "Effect of Female Age on Mouse Oocyte Developmental Competence Following Mitochondrial Injury,"Biol. Reprod. 73, 366 - 373 (2005).
[CrossRef] [PubMed]

Tinneberg, H.-R.

Y. Shen, T. Stalf, C. Mehnert, U. Eichenlaub-Ritter, and H.-R. Tinneberg, "High magnitude of light retardation by the zona pellucida is associated with conception cycles," Hum. Reprod. 20, 1596-1606 (2005).
[CrossRef] [PubMed]

Tokura, T.

T.  Tokura, Y.  Noda, Y.  Goto, and T.  Mori, "Sequential observation of mitochondrial distribution in mouse oocytes and embryos," J. Assist. Reprod. Genet. 10, 417-426 (1993).
[CrossRef] [PubMed]

Tordjmann, T.

D. Debarre, W. Supatto, A. M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M. C. Schanne-Klein, and E. Beaurepaire, "Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy," Nat. Methods 3, 47-53 (2006).
[CrossRef]

Tran, P.

D. Keefe, P. Tran, C. Pellegrini, and R. Oldenbourg, "Polarized light microscopy and digital image processing identify a multilaminar structure of the hamster zona pellucida," Hum. Reprod. 12, 1250-1252 (1997).
[CrossRef] [PubMed]

Trimarchi, J. R.

C. Pelletier, D. L. Keefe, and J. R. Trimarchi, "Noninvasive polarized light microscopy quantitatively distinguishes the multilaminar structure of the zona pellucida of living human eggs and embryos," Fertil. Steril. 81, 850-856 (2004).
[CrossRef] [PubMed]

Trounson, A. O.

G. A. Thouas, A. O. Trounson, and G. M. Jones, "Effect of Female Age on Mouse Oocyte Developmental Competence Following Mitochondrial Injury,"Biol. Reprod. 73, 366 - 373 (2005).
[CrossRef] [PubMed]

Tsai, H.-J.

C.-K. Sun, S.-W. Chu, S.-Y. Chen, T.-H. Tsai, T.-M. Liu, C.-Y. Lin, and H.-J. Tsai, "Higher harmonic generation microscopy for developmental biology," J. Struct. Bio. 147, 19-30 (2004).
[CrossRef]

S.-W. Chu, S.-Y. Chen, T.-H. Tsai, T.-M. Liu, C.-Y. Lin, H.-J. Tsai, and C.-K. Sun, "In vivo developmental biology study using noninvasive multi-harmonic generation microscopy," Opt. Express 11, 3093-3099 (2003).
[CrossRef] [PubMed]

S.-Y. Chen, C.-S. Hsieh, S.-W. Chu, C.-Y. Ko, Y.-C. Chen, H.-J. Tsai, C.-H. Hu, C.-K. Sun, "Noninvasive harmonics optical microscopy for long-term observation of embryonic nervous system development in vivo. "J. Biom. Opt. 11, 054022 1-8 (2006).

Tsai, T.-H.

S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of ???(2)/???(3) tensors in submicron-scaled bio-tissues by polarization harmonics optical microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

C.-K. Sun, S.-W. Chu, S.-Y. Chen, T.-H. Tsai, T.-M. Liu, C.-Y. Lin, and H.-J. Tsai, "Higher harmonic generation microscopy for developmental biology," J. Struct. Bio. 147, 19-30 (2004).
[CrossRef]

S.-W. Chu, S.-Y. Chen, T.-H. Tsai, T.-M. Liu, C.-Y. Lin, H.-J. Tsai, and C.-K. Sun, "In vivo developmental biology study using noninvasive multi-harmonic generation microscopy," Opt. Express 11, 3093-3099 (2003).
[CrossRef] [PubMed]

Tsai, Y.-Y.

S.-U. Chen, T.-H. Lee, Y.-R. Lien, Y.-Y. Tsai, L.-J. Chang, and Y.-S. Yang, "Microsuction of blastocoelic fluid before vitrification increased survival and pregnancy of mouse expanded blastocysts, but pretreatment with the cytoskeletal stabilizer did not increase blastocyst survival," Fertil. Steril. 84, 1156-1162 (2005).
[CrossRef] [PubMed]

Tsang, T. Y. F.

T. Y. F. Tsang, "Optical 3rd-harmonic generation at interfaces," Phys. Rev. A 52, 4116-4125 (1995).
[CrossRef]

Tureck, R. W.

W. T. Garside, J. R. L. D. Mola, J. A. Bucci, R. W. Tureck, S. Heyner, "Sequential analysis of zona thickness during in vitro culture of human zygotes: Correlation with embryo quality, age, and implantation," Mol. Reprod. Dev.47, 99-104 (1997).
[CrossRef] [PubMed]

Tyler, J. P. P.

S. Cooke, J. P. P. Tyler, G. L. Driscoll, "Meiotic spindle location and identification and its effect on embryonic cleavage plane and early development," Hum. Reprod. 18,2397-2405 (2003)
[CrossRef] [PubMed]

van Beek, J. H.

van Haaften, M.

J. P. de Bruin, M. Dorland, E. R. Spek, G. Posthuma, M. van Haaften, C. W. Looman, and E. R. te Velde, "Age-related changes in the ultrastructure of the resting follicle pool in human ovaries," Biol. Reprod. 70, 419-424 (2004).
[CrossRef]

Wang, I.-J.

Wassarman, P. M.

J. C. Bleil and P. M. Wassarman, "Structure and function for the zona pellucida: identification and characterization of the proteins of the mouse oocyte's zona pellucida," Dev. Biol. 76, 185-202 (1980).
[CrossRef] [PubMed]

Weakley, B. S.

B. S.  Weakley, P.  Webb, and J. L.  James, "Cytochemistry of the Golgi apparatus in developing ovarian germ cells of the Syrian hamster," Cell Tissue Res. 220, 349-372 (1981).
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Webb, P.

B. S.  Weakley, P.  Webb, and J. L.  James, "Cytochemistry of the Golgi apparatus in developing ovarian germ cells of the Syrian hamster," Cell Tissue Res. 220, 349-372 (1981).
[CrossRef] [PubMed]

White, J. G.

J. M. Squirell, D. L. Wokosin, J. G. White, and B. D. Bavister, "Long-term two-photon fluorescence imaging of mammalian embryos without compromising viability," Nat. Biotechnol. 17, 763-767 (1999).
[CrossRef]

Wilson, K. R.

J. A. Squier, M. Muller, and G. J. Brakenhoff, and K. R. Wilson, "Third harmonic generation microscopy," Opt. Express 3, 315-324 (1998).
[CrossRef] [PubMed]

M. Muller, J. Squier, K. R. Wilson, and G. J. Brakenhoff, "3D microscopy of transparent objects using third-harmonic generation," J. Microsc.-Oxford 191, 266-274 (1998).
[CrossRef]

A. C. Millard, D. N. Fittinghoff, P. W. Wiseman, M. Muller, G. J. Brakenhoff, J. A. Squier, and K. R. Wilson, "Three dimensional, third harmonic microscopy of living systems," Biophys. J. 78, 800Plat Part 2 (2000).

Wiseman, P. W.

A. C. Millard, D. N. Fittinghoff, P. W. Wiseman, M. Muller, G. J. Brakenhoff, J. A. Squier, and K. R. Wilson, "Three dimensional, third harmonic microscopy of living systems," Biophys. J. 78, 800Plat Part 2 (2000).

Wokosin, D. L.

J. M. Squirell, D. L. Wokosin, J. G. White, and B. D. Bavister, "Long-term two-photon fluorescence imaging of mammalian embryos without compromising viability," Nat. Biotechnol. 17, 763-767 (1999).
[CrossRef]

Yamamasu, S.

Y. Fujino, K. Ozaki, S. Yamamasu, F. Ito, I. Matsuoka, E. Hayashi, H. Nakamura, S. Ogita, E. Sato, and M. Inoue, "DNA fragmentation of oocytes in aged mice," Hum. Reprod. 11, 1480-1483 (1996).
[PubMed]

Yang, Y.-S.

S.-U. Chen, Y.-R. Lien, Y.-Y. Cheng, H.-F. Chen, H.-N. Ho, and Y.-S. Yang, "Vitrification of mouse oocytes using closed pulled straws (CPS) achieves a high survival and preserves good patterns of meiotic spindles, compared with conventional straws, open pulled straws (OPS) and grids," Hum. Reprod. 16, 2350 - 2356 (2001).
[PubMed]

S.-U. Chen, T.-H. Lee, Y.-R. Lien, Y.-Y. Tsai, L.-J. Chang, and Y.-S. Yang, "Microsuction of blastocoelic fluid before vitrification increased survival and pregnancy of mouse expanded blastocysts, but pretreatment with the cytoskeletal stabilizer did not increase blastocyst survival," Fertil. Steril. 84, 1156-1162 (2005).
[CrossRef] [PubMed]

Yu, C.-H.

Yu, H.-C.

Am. J. Anat. (1)

J. V. Blerkom, M. N. Runner, "Mitochondrial reorganization during resumption of arrested meiosis in the mouse oocyte," Am. J. Anat. 171, 335-355(1984).
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Y. Barad, H. Eisenberg, M. Horowitz, and Y. Silberberg, "Nonlinear scanning laser microscopy by third harmonic generation," App. Phy. Lett. 70, 922-924 (1997).
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Arch. Histol. Cytol. (1)

P. M. Motta, S. Makabe, T. Naguro, and S. Correr, "Oocyte follicle cells association during development of human ovarian follicle. A study by high resolution scanning and transmission electron microscopy," Arch. Histol. Cytol. 57, 369-394 (1994).
[CrossRef] [PubMed]

Biol. Reprod. (3)

J. P. de Bruin, M. Dorland, E. R. Spek, G. Posthuma, M. van Haaften, C. W. Looman, and E. R. te Velde, "Age-related changes in the ultrastructure of the resting follicle pool in human ovaries," Biol. Reprod. 70, 419-424 (2004).
[CrossRef]

G. A. Thouas, A. O. Trounson, and G. M. Jones, "Effect of Female Age on Mouse Oocyte Developmental Competence Following Mitochondrial Injury,"Biol. Reprod. 73, 366 - 373 (2005).
[CrossRef] [PubMed]

R. D. Moreno, G. Schatten, and J. Ramalho-Santos, "Golgi apparatus dynamics during mouse oocyte in vitro maturation: effect of the membrane trafficking inhibitor brefeldin A," Biol. Reprod. 66, 1259-1266 (2002)
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Biophys. J. (3)

P. J. Campagnola, A. C. Millard, M. Terasaki, P. E. Hoppe, C. J. Malone, and W. A. Mohler, "Three dimensional high-resolution second-harmonic generation imaging of endogenous structural proteins in biological tissues," Biophys. J. 82, 493-508 (2002).
[CrossRef]

P. Stoller, K. M. Reiser, P. M. Celliers, and A. M. Rubenchik, "Polarization-modulated second harmonic generation in collagen," Biophys. J. 82, 3330-3342 (2002).
[CrossRef] [PubMed]

S.-W. Chu, S.-Y. Chen, G.-W. Chern, T.-H. Tsai, Y.-C. Chen, B.-L. Lin, and C.-K. Sun, "Studies of ???(2)/???(3) tensors in submicron-scaled bio-tissues by polarization harmonics optical microscopy," Biophys. J. 86, 3914-3922 (2004).
[CrossRef] [PubMed]

Dev. Biol. (3)

J. C. Bleil and P. M. Wassarman, "Structure and function for the zona pellucida: identification and characterization of the proteins of the mouse oocyte's zona pellucida," Dev. Biol. 76, 185-202 (1980).
[CrossRef] [PubMed]

G. FitzHarris, P. Marangos, and J. Carroll, "Changes in endoplasmic reticulum structure during mouse oocyte maturation are controlled by the cytoskeleton and cytoplasmic dynein," Dev. Biol. 305, 133-144 (2007).
[CrossRef] [PubMed]

L. M. Mehlmann, M. Terasaki, L. A. Jaffe, D. Kline, "Reorganization of the endoplasmic reticulum during meiotic maturation of the mouse oocyte," Dev. Biol. 170, 607-615 (1995).
[CrossRef] [PubMed]

Hum. Reprod. (11)

J. V. Blerkom, P. Davis, V. Mathwig, and S. Alexander, "Domains of high-polarized and low-polarized mitochondria may occur in mouse and human oocytes and early embryos" Hum. Reprod. 17, 393-406 (2002).
[CrossRef] [PubMed]

L. Liu and D. L. Keefe, "Ageing-associated aberration in meiosis of oocytes from senescence-accelerated mice," Hum. Reprod. 17, 2678-2685 (2002).
[CrossRef] [PubMed]

S. Cooke, J. P. P. Tyler, G. L. Driscoll, "Meiotic spindle location and identification and its effect on embryonic cleavage plane and early development," Hum. Reprod. 18,2397-2405 (2003)
[CrossRef] [PubMed]

J. Holte, L.  Berglund, K.  Milton, C.  Garello, G.  Gennarelli, A.  Revelli, T.  Bergh, "Construction of an evidence-based integrated morphology cleavage embryo score for implantation potential of embryos scored and transferred on day 2 after oocyte retrieval," Hum. Reprod. 22, 548-557 (2007)
[CrossRef]

Y. Shen, T. Stalf, C. Mehnert, U. Eichenlaub-Ritter, and H.-R. Tinneberg, "High magnitude of light retardation by the zona pellucida is associated with conception cycles," Hum. Reprod. 20, 1596-1606 (2005).
[CrossRef] [PubMed]

J. V. Blerkom and G. Henry, "Oocyte dysmorphism and aneuploidy in meiotically mature human oocytes after ovarian stimulation," Hum. Reprod. 7, 379-390 (1992).
[PubMed]

S.-U. Chen, Y.-L. Lien, and H.-F. Chen, "Open pulled straws for vitrification of mature mouse oocytes preserve patterns of meiotic spindles and chromosomes better than conventional straws," Hum. Reprod. 15, 2598-2603 (2000).
[CrossRef] [PubMed]

S.-U. Chen, Y.-R. Lien, Y.-Y. Cheng, H.-F. Chen, H.-N. Ho, and Y.-S. Yang, "Vitrification of mouse oocytes using closed pulled straws (CPS) achieves a high survival and preserves good patterns of meiotic spindles, compared with conventional straws, open pulled straws (OPS) and grids," Hum. Reprod. 16, 2350 - 2356 (2001).
[PubMed]

D. Keefe, P. Tran, C. Pellegrini, and R. Oldenbourg, "Polarized light microscopy and digital image processing identify a multilaminar structure of the hamster zona pellucida," Hum. Reprod. 12, 1250-1252 (1997).
[CrossRef] [PubMed]

Y. Fujino, K. Ozaki, S. Yamamasu, F. Ito, I. Matsuoka, E. Hayashi, H. Nakamura, S. Ogita, E. Sato, and M. Inoue, "DNA fragmentation of oocytes in aged mice," Hum. Reprod. 11, 1480-1483 (1996).
[PubMed]

J. Otsuki, A. Okada, K. Morimoto, Y. Nagai, and H. Kubo, "The relationship between pregnancy outcome and smooth endoplasmic reticulum clusters in MII human oocytes," Hum. Reprod. 19, 1591-1597 (2004).
[CrossRef] [PubMed]

J. Assist. Reprod. Genet. (3)

S. D. Spandorfer, P. H. Chung, I. Kligman, H. C. Liu, O. K. Davis, and Z. Rosenwal, "An analysis of the effect of age on implantation rates," J. Assist. Reprod. Genet. 17, 303-306 (2000).
[CrossRef] [PubMed]

T.  Tokura, Y.  Noda, Y.  Goto, and T.  Mori, "Sequential observation of mitochondrial distribution in mouse oocytes and embryos," J. Assist. Reprod. Genet. 10, 417-426 (1993).
[CrossRef] [PubMed]

A. Gabrielsen, P.R. Bhatnager, K. Petersen and S. Lindenberg, "Influence of zona pellucida thickness of human embryos on clinical pregnancy outcome following in vitro fertilization treatment," J. Assist. Reprod. Genet. 17, 323-328 (2000).
[CrossRef] [PubMed]

J. Exp. Zool. (1)

D. M. Phillips, R. M. Shalgi, "Surface properties of the zona pellucida," J. Exp. Zool. 213, 1-8 (1980).
[CrossRef] [PubMed]

J. Struct. Bio. (1)

C.-K. Sun, S.-W. Chu, S.-Y. Chen, T.-H. Tsai, T.-M. Liu, C.-Y. Lin, and H.-J. Tsai, "Higher harmonic generation microscopy for developmental biology," J. Struct. Bio. 147, 19-30 (2004).
[CrossRef]

Microsc. Microanal. (1)

M. Shribak, J. LaFountain, D. Biggs, and S. Inoué, "Quantitative orientation-independent differential interference contrast (DIC) microscopy coupled with orientation-independent polarization microscopy," Microsc. Microanal. 13, 10-11 (2007).
[PubMed]

Microsc. Res. Tech. (2)

S.-W. Chu, S.-P. Tai, C.-L. Ho, C.-H. Lin, and C.-K Sun, "High-resolution simultaneous three-photon fluorescence and third-harmonic-generation microscopy," Microsc. Res. Tech. 66, 193-197 (2005).
[CrossRef] [PubMed]

D. F. Albertini and V. Rider, "Patterns of intercellular connectivity in the mammalian cumulus-oocyte complex," Microsc. Res. Tech. 27, 125-133 (1994).
[CrossRef] [PubMed]

Mol. Biol. Cell (3)

S. Inoué, and R. Oldenbourg, "Microtubule dynamics in mitotic spindle displayed by polarized light microscopy," Mol. Biol. Cell 9, 1603-1607 (1998).
[PubMed]

M. Terasaki, L. L. Runft, and A. R. Hand, "Changes in organization of the endoplasmic reticulum during Xenopus oocyte maturation and activation," Mol. Biol. Cell 12, 1103-1116 (2001)
[PubMed]

G. Fitzharris, P. Marangos, and J. Carroll, "Cell cycle-dependent regulation of structure of endoplasmic reticulum and inositol 1, 4, 5-trisphosphate-induced Ca2+ release in mouse oocytes and embryos," Mol. Biol. Cell 14, 288-301 (2003).
[CrossRef] [PubMed]

Nat. Biotechnol. (1)

J. M. Squirell, D. L. Wokosin, J. G. White, and B. D. Bavister, "Long-term two-photon fluorescence imaging of mammalian embryos without compromising viability," Nat. Biotechnol. 17, 763-767 (1999).
[CrossRef]

Nat. Methods (1)

D. Debarre, W. Supatto, A. M. Pena, A. Fabre, T. Tordjmann, L. Combettes, M. C. Schanne-Klein, and E. Beaurepaire, "Imaging lipid bodies in cells and tissues using third-harmonic generation microscopy," Nat. Methods 3, 47-53 (2006).
[CrossRef]

Opt. Express (5)

Opt. Lett. (2)

Phys. Rev. A (1)

T. Y. F. Tsang, "Optical 3rd-harmonic generation at interfaces," Phys. Rev. A 52, 4116-4125 (1995).
[CrossRef]

Reproduction (1)

D. F. Albertini and S. L. Barrett, "Oocyte-somatic cell communication," Reproduction 61 (Suppl), 49-54 (2003).
[PubMed]

Other (10)

M. Muller, J. Squier, K. R. Wilson, and G. J. Brakenhoff, "3D microscopy of transparent objects using third-harmonic generation," J. Microsc.-Oxford 191, 266-274 (1998).
[CrossRef]

S.-W. Chu, I.-H. Chen, T.-M. Liu, C.-K. Sun, S.-P. Lee, B.-L. Lin, P.-C. Cheng, M.-X. Kuo, D.-J. Lin, and H.-L. Liu, "Nonlinear bio-photonic crystal effects revealed with multimodal nonlinear microscopy," J. Microsc.-Oxford 208, 190-200 (2002).
[CrossRef]

S.-U. Chen, T.-H. Lee, Y.-R. Lien, Y.-Y. Tsai, L.-J. Chang, and Y.-S. Yang, "Microsuction of blastocoelic fluid before vitrification increased survival and pregnancy of mouse expanded blastocysts, but pretreatment with the cytoskeletal stabilizer did not increase blastocyst survival," Fertil. Steril. 84, 1156-1162 (2005).
[CrossRef] [PubMed]

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Figures (9)

Fig. 1.
Fig. 1.

Depth-resolved section series with combined SHG and THG signals inside a live mouse embryo at the 2–cells stage. (A) – (H) were acquired at imaging depths from 0μm to 63μm relative to (A) with a step of 9μm. The SHG and THG signals are denoted by green and blue colors, respectively. Scale bar: 60μm.

Fig. 2.
Fig. 2.

HGM sectioned images of the in vitro cultured mouse (A) oocyte and (B)–(I) embryos. (A) The SHG signals reveal the spindle fibers (indicated by the yellow arrow) and the zona pellucida (indicated by the white arrow) of the oocyte, while the THG signals reveals the cell membrane, the organelles, and the polar body (indicated by the red arrow). (B) and (C) are images of the same mouse embryo at the 2P stage taken at different depths. The white arrows indicate the two pronuclei. (D)–(H) are images of mouse embryos at the 2–cells, 4–cells, 8–cells uncompacted, 8–cells compacted, and morula stages, respectively. (I) After cavitation, the embryo developed the blastocoel (indicated by the yellow arrow), the trophectoderm (indicated by the white arrow), the inner cell mass (indicated by the red arrow), and turned into a blastocyst. The SHG and THG signals are denoted by green and blue colors, respectively. Scale bar: 60μm

Fig. 3.
Fig. 3.

Normalized nonlinear emission spectra from the organelles labeled by 5 different dyes. The black, red, and blue curves are the spectra measured from the BODIPY FL C5–ceramide labeled Golgi apparatus, ER–Tracker Blue-White DPX labeled ER, and MitoTracker Red CMH2XRos labeled mitochondria, respectively. The green and light blue curves are spectra measured from lysosomes labeled by LysoSensor Green DND189 and LysoTracker Red Lysosomal Probe, respectively. The peak at 410nm represents the THG signals.

Fig 4.
Fig 4.

(A) (D), (G), (J), (M) THG (shown in blue) and (B), (E), (H), (K), (N) multiphoton fluorescence (shown in red) images of in vitro stained mouse oocytes. (C), (F), (I), (L), (O) are the combined THG/fluorescence images. (A)–(C) are images of an oocyte stained with BODIPY FL C5–ceramide. (D)–(F) are images of an oocyte stained with ER-Tracker Blue- White DPX. (G)–(I) are images of an oocyte stained with MitoTracker Red CM-H2XRos. (J)–(L) are images of an oocyte stained with LysoSensor Green DND189. (M)–(O) are images of an oocyte stained with LysoTracker Red Lysosomal Probe. Scale bar: 60μm.

Fig. 5.
Fig. 5.

Pearson’s correlation of THG and fluorescence signals revealed from mouse (A) oocytes and (B) embryos stained with BF: BODIPY FL C5–ceramide, EB: ER-Tracker Blue-White DPX, MR: MitoTracker Red CM-H2XRos, LG: LysoSensor Green DND189, and LR: LysoTracker Red Lysosomal Probe, respectively.

Fig. 6.
Fig. 6.

(A) SHG image of a mouse embryo at the morula stage. (B) Enlarged image corresponding to the squared area in (A), which can distinguish the three layers of zona pellucida. (C) The vertical position dependent SHG intensity after integration along the horizontal direction. Scale bar: 60μm.

Fig. 7.
Fig. 7.

(A) In vitro HGM image sectioned through the center of a mouse oocyte. Following (A), (B) and (C) show the SHG intensity of the (B) IL and (C) OL as a function of the angle θ between the laser polarization and the normal vector to the surface of the zona pellucida. Red lines are fitting curves following Eq. (3). Scale bar: 60μm.

Fig 8.
Fig 8.

Born mice of the experiment set. Among the implanted 18 embryos, 12 mice were hatched, with a ratio similar to the control set.

Fig. 9.
Fig. 9.

In vitro HGM images of oocytes obtained from (A) pubertal (4–6 weeks) and (B), (C) aging (> 8 months) mice. Scale bar: 60μm.

Equations (3)

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r = i = 1 n ( X i X - ) ( Y i Y - ) ( n 1 ) S X S Y ,
P ( 2 ) = a ŝ ( ŝ E ) 2 + b ŝ E 2 + c E ( ŝ E )
I SHG E 4 { ( d 31 sin 2 θ + d 33 cos 2 θ ) 2 + d 15 2 sin 2 ( 2 θ ) } ,

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