Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Putrescine supplementation during in vitro maturation of aged mouse oocytes improves the quality of blastocysts

Dandan Liu A B C F * , Guolong Mo A D * , Yong Tao A , Hongmei Wang B C G and X. Johné Liu A D E G
+ Author Affiliations
- Author Affiliations

A Ottawa Hospital Research Institute, The Ottawa Hospital ­– General Campus, 501 Smyth Road, Box 511, Ottawa, ON, K1H 8L6, Canada.

B State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.

C University of Chinese Academy of Sciences, Beijing, 100049, China.

D Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, K1H 8L6, Canada.

E Department of Obstetrics and Gynaecology, University of Ottawa, Ottawa, ON, K1H 8L6, Canada.

F Present address: Centre of Reproductive Medicine, Department of Obstetrics and Gynaecology, Peking University Third Hospital, 49 North Huayuan Road, Haidian District, Beijing, 100191, China.

G Corresponding authors. Emails: wanghm@ioz.ac.cn; jliu@ohri.ca

Reproduction, Fertility and Development 29(7) 1392-1400 https://doi.org/10.1071/RD16061
Submitted: 5 February 2016  Accepted: 12 May 2016   Published: 20 June 2016

Abstract

Mouse ovaries exhibit a peri-ovulatory rise of ornithine decarboxylase and its product putrescine concurrent with oocyte maturation. Older mice exhibit a deficiency of both the enzyme and putrescine. Peri-ovulatory putrescine supplementation in drinking water increases ovarian putrescine levels, reduces embryo resorption and increases live pups in older mice. However, it is unknown if putrescine acts in the ovaries to improve oocyte maturation. This study examined the impact of putrescine supplementation during oocyte in vitro maturation (IVM) on the developmental potential of aged oocytes. Cumulus–oocyte complexes from 9–12-month-old C57BL/6 mice were subjected to IVM with or without 0.5 mM putrescine, followed by in vitro fertilisation and culture to the blastocyst stage. Putrescine supplementation during IVM did not influence the proportion of oocyte maturation, fertilisation or blastocyst formation, but significantly increased blastocyst cell numbers (44.5 ± 1.9, compared with 36.5 ± 1.9 for control; P = 0.003). The putrescine group also had a significantly higher proportion of blastocysts with top-grade morphology (42.9%, compared with 26.1% for control; P = 0.041) and a greater proportion with octamer-binding transcription factor 4 (OCT4)-positive inner cell mass (38.3%, compared with 19.8% for control; P = 0.005). Therefore, putrescine supplementation during IVM improves egg quality of aged mice, providing proof of principle for possible application in human IVM procedures for older infertile women.

Additional keywords: aging, inner cell mass, in vitro fertilisation (IVF).


References

Alhonen, L., Halmekyto, M., Kosma, V. M., Wahlfors, J., Kauppinen, R., and Janne, J. (1995). Life-long over-expression of ornithine decarboxylase (ODC) gene in transgenic mice does not lead to generally enhanced tumorigenesis or neuronal degeneration. Int. J. Cancer 63, 402–404.
Life-long over-expression of ornithine decarboxylase (ODC) gene in transgenic mice does not lead to generally enhanced tumorigenesis or neuronal degeneration.CrossRef | 1:CAS:528:DyaK28Xjslyh&md5=ae1c4d250414eec9c5e51f5d6b2a5ffcCAS | 7591239PubMed | open url image1

Baltus, A. E., Menke, D. B., Hu, Y. C., Goodheart, M. L., Carpenter, A. E., de Rooij, D. G., and Page, D. C. (2006). In germ cells of mouse embryonic ovaries, the decision to enter meiosis precedes premeiotic DNA replication. Nat. Genet. 38, 1430–1434.
In germ cells of mouse embryonic ovaries, the decision to enter meiosis precedes premeiotic DNA replication.CrossRef | 1:CAS:528:DC%2BD28Xht1CntrfP&md5=696965c48b2123621b2286932d3ffc23CAS | 17115059PubMed | open url image1

Bastida, C. M., Cremades, A., Castells, M. T., Lopez-Contreras, A. J., Lopez-Garcia, C., Tejada, F., and Penafiel, R. (2005). Influence of ovarian ornithine decarboxylase in folliculogenesis and luteinization. Endocrinology 146, 666–674.
Influence of ovarian ornithine decarboxylase in folliculogenesis and luteinization.CrossRef | 1:CAS:528:DC%2BD2MXotlWiuw%3D%3D&md5=00de009016961602bc62d623c55b6839CAS | 15514084PubMed | open url image1

Bieniarz, A., Berger, T., Nishimura, K., and diZerega, G. S. (1983). Ibuprofen modulation of human chorionic gonadotropin-induced ornithine decarboxylase activity and ovulation in the rabbit ovary. Am. J. Obstet. Gynecol. 147, 327–332.
Ibuprofen modulation of human chorionic gonadotropin-induced ornithine decarboxylase activity and ovulation in the rabbit ovary.CrossRef | 1:CAS:528:DyaL3sXlvVymtb8%3D&md5=0a398a73ec64360abab53403f0aa5af2CAS | 6624798PubMed | open url image1

Biggers, J. D., Bell, J. E., and Benos, D. J. (1988). Mammalian blastocyst: transport functions in a developing epithelium. Am. J. Physiol. 255, C419–C432.
| 1:CAS:528:DyaL1cXmtVylurk%3D&md5=078d1d0ecefae672350b7edd8812de57CAS | 3052100PubMed | open url image1

Byers, S. L., Wiles, M. V., Dunn, S. L., and Taft, R. A. (2012). Mouse estrous cycle identification tool and images. PLoS One 7, e35538.
Mouse estrous cycle identification tool and images.CrossRef | 1:CAS:528:DC%2BC38Xmt1ehsrk%3D&md5=8333c0805e2ae87b00becd0f8d6fc200CAS | 22514749PubMed | open url image1

Chang, H. C., Liu, H., Zhang, J., Grifo, J., and Krey, L. C. (2005). Developmental incompetency of denuded mouse oocytes undergoing maturation in vitro is ooplasmic in nature and is associated with aberrant Oct-4 expression. Hum. Reprod. 20, 1958–1968.
Developmental incompetency of denuded mouse oocytes undergoing maturation in vitro is ooplasmic in nature and is associated with aberrant Oct-4 expression.CrossRef | 1:CAS:528:DC%2BD2MXmvF2ksro%3D&md5=05900ff474ff59cd44dd0cfe9ff69d4bCAS | 15817588PubMed | open url image1

Delle Piane, L., Lin, W., Liu, X., Donjacour, A., Minasi, P., Revelli, A., Maltepe, E., and Rinaudo, P. F. (2010). Effect of the method of conception and embryo transfer procedure on mid-gestation placenta and fetal development in an IVF mouse model. Hum. Reprod. 25, 2039–2046.
Effect of the method of conception and embryo transfer procedure on mid-gestation placenta and fetal development in an IVF mouse model.CrossRef | 1:STN:280:DC%2BC3cnos1ensQ%3D%3D&md5=e341b2f5328661fd1118b974e557da24CAS | 20576634PubMed | open url image1

Eichenlaub-Ritter, U., Wieczorek, M., Luke, S., and Seidel, T. (2011). Age related changes in mitochondrial function and new approaches to study redox regulation in mammalian oocytes in response to age or maturation conditions. Mitochondrion 11, 783–796.
Age related changes in mitochondrial function and new approaches to study redox regulation in mammalian oocytes in response to age or maturation conditions.CrossRef | 1:CAS:528:DC%2BC3MXhtVWrsr%2FF&md5=66941721522c4e6293474b712c6acaa5CAS | 20817047PubMed | open url image1

Eppig, J. J. (1982). The relationship between cumulus cell–oocyte coupling, oocyte meiotic maturation, and cumulus expansion. Dev. Biol. 89, 268–272.
The relationship between cumulus cell–oocyte coupling, oocyte meiotic maturation, and cumulus expansion.CrossRef | 1:STN:280:DyaL38%2FpsF2msw%3D%3D&md5=62ee8e16fcf60a161a68c9482c618bafCAS | 7054011PubMed | open url image1

Eppig, J. J., Schultz, R. M., O’Brien, M., and Chesnel, F. (1994). Relationship between the developmental programs controlling nuclear and cytoplasmic maturation of mouse oocytes. Dev. Biol. 164, 1–9.
Relationship between the developmental programs controlling nuclear and cytoplasmic maturation of mouse oocytes.CrossRef | 1:STN:280:DyaK2c3pvFSjtA%3D%3D&md5=ca833897b41198e6480f615acaf7ffefCAS | 8026614PubMed | open url image1

Fozard, J. R., Prakash, N. J., and Grove, J. (1980). Ovarian function in the rat following irreversible inhibition of L-ornithine decarboxylase. Life Sci. 27, 2277–2283.
Ovarian function in the rat following irreversible inhibition of L-ornithine decarboxylase.CrossRef | 1:CAS:528:DyaL3MXksV2mtQ%3D%3D&md5=8d7789613981321b34295a1dd0322b19CAS | 6782405PubMed | open url image1

Grant, A. L., Holland, R. E., Thomas, J. W., King, K. J., and Liesman, J. S. (1989). Effects of dietary amines on the small intestine in calves fed soybean protein. J. Nutr. 119, 1034–1041.
| 1:CAS:528:DyaL1MXltlejtrw%3D&md5=b37886246fb934df3b70627e86cc5489CAS | 2754510PubMed | open url image1

Grant, A. L., Thomas, J. W., King, K. J., and Liesman, J. S. (1990). Effects of dietary amines on small intestinal variables in neonatal pigs fed soy protein isolate. J. Anim. Sci. 68, 363–371.
| 1:CAS:528:DyaK3cXhsFOisrk%3D&md5=49c0d5611ece78903951fc3f394a0537CAS | 1690199PubMed | open url image1

Hardarson, T., Caisander, G., Sjogren, A., Hanson, C., Hamberger, L., and Lundin, K. (2003). A morphological and chromosomal study of blastocysts developing from morphologically suboptimal human pre-embryos compared with control blastocysts. Hum. Reprod. 18, 399–407.
A morphological and chromosomal study of blastocysts developing from morphologically suboptimal human pre-embryos compared with control blastocysts.CrossRef | 1:CAS:528:DC%2BD3sXit1yrtLw%3D&md5=7c50d915c8aec8f0cce57e96e98b101eCAS | 12571180PubMed | open url image1

Hardy, K., Handyside, A. H., and Winston, R. M. (1989). The human blastocyst: cell number, death and allocation during late preimplantation development in vitro. Development 107, 597–604.
| 1:STN:280:DyaK3c7is1eruw%3D%3D&md5=c7a0b59e715509cd217b85650fb7e00eCAS | 2612378PubMed | open url image1

Hassold, T., and Hunt, P. (2001). To err (meiotically) is human: the genesis of human aneuploidy. Nat. Rev. Genet. 2, 280–291.
To err (meiotically) is human: the genesis of human aneuploidy.CrossRef | 1:CAS:528:DC%2BD3MXisVCqurY%3D&md5=a69a6eec7d8bb2cf4fbe04950d41535fCAS | 11283700PubMed | open url image1

Holinka, C. F., Tseng, Y. C., and Finch, C. E. (1979). Reproductive aging in C57BL/6J mice: plasma progesterone, viable embryos and resorption frequency throughout pregnancy. Biol. Reprod. 20, 1201–1211.
Reproductive aging in C57BL/6J mice: plasma progesterone, viable embryos and resorption frequency throughout pregnancy.CrossRef | 1:CAS:528:DyaE1MXkvVyhurY%3D&md5=0624dbe21747561cde65be399e80d2c1CAS | 476251PubMed | open url image1

Icekson, I., Kaye, A. M., Lieberman, M. E., Lamprecht, S. A., Lahav, M., and Lindner, H. R. (1974). Stimulation by luteinizing hormone of ornithine decarboxylase in rat ovary: preferential response by follicular tissue. J. Endocrinol. 63, 417–418.
Stimulation by luteinizing hormone of ornithine decarboxylase in rat ovary: preferential response by follicular tissue.CrossRef | 1:CAS:528:DyaE2MXkt1aktr4%3D&md5=083264ff11bec10fd0216214a4bd7176CAS | 4475085PubMed | open url image1

Kobayashi, Y., Kupelian, J., and Maudsley, D. V. (1971). Ornithine decarboxylase stimulation in rat ovary by luteinizing hormone. Science 172, 379–380.
Ornithine decarboxylase stimulation in rat ovary by luteinizing hormone.CrossRef | 1:CAS:528:DyaE3MXktFGltr8%3D&md5=21bb7ead73f4d33f1151c81ba93da742CAS | 5102475PubMed | open url image1

Kong, X., Wang, X., Yin, Y., Li, X., Gao, H., Bazer, F. W., and Wu, G. (2014). Putrescine stimulates the mTOR signaling pathway and protein synthesis in porcine trophectoderm cells. Biol. Reprod. 91, 106.
Putrescine stimulates the mTOR signaling pathway and protein synthesis in porcine trophectoderm cells.CrossRef | 25253735PubMed | open url image1

Lane, M., and Gardner, D. K. (1997). Differential regulation of mouse embryo development and viability by amino acids. J. Reprod. Fertil. 109, 153–164.
Differential regulation of mouse embryo development and viability by amino acids.CrossRef | 1:CAS:528:DyaK2sXhs1Gls78%3D&md5=03dc8910020311e4d4d448c92880d6c1CAS | 9068427PubMed | open url image1

Lawitts, J. A., and Graves, C. N. (1988). Viability of mouse half-embryos in vitro and in vivo. Gamete Res. 20, 421–430.
Viability of mouse half-embryos in vitro and in vivo.CrossRef | 1:STN:280:DyaL1M7nt1Omtg%3D%3D&md5=0e1f76e5bd71d07e80ab735811d27f6aCAS | 3235050PubMed | open url image1

Lei, L., and Spradling, A. C. (2013). Female mice lack adult germ-line stem cells but sustain oogenesis using stable primordial follicles. Proc. Natl. Acad. Sci. USA 110, 8585–8590.
Female mice lack adult germ-line stem cells but sustain oogenesis using stable primordial follicles.CrossRef | 1:CAS:528:DC%2BC3sXhtFSgtL3N&md5=1581e4b20bb7dc98e35e626d4a141770CAS | 23630252PubMed | open url image1

Liu, X. J. (2016). Targeting oocyte maturation to improve fertility in older women. Cell Tissue Res. 363, 57–68.
Targeting oocyte maturation to improve fertility in older women.CrossRef | 26329301PubMed | open url image1

Luke, B., Brown, M. B., Wantman, E., Lederman, A., Gibbons, W., Schattman, G. L., Lobo, R. A., Leach, R. E., and Stern, J. E. (2012). Cumulative birth rates with linked assisted reproductive technology cycles. N. Engl. J. Med. 366, 2483–2491.
Cumulative birth rates with linked assisted reproductive technology cycles.CrossRef | 1:CAS:528:DC%2BC38XhtV2qtrvP&md5=e207681aa559f96737830f3279e9a821CAS | 22738098PubMed | open url image1

Marikawa, Y., and Alarcon, V. B. (2009). Establishment of trophectoderm and inner cell mass lineages in the mouse embryo. Mol. Reprod. Dev. 76, 1019–1032.
Establishment of trophectoderm and inner cell mass lineages in the mouse embryo.CrossRef | 1:CAS:528:DC%2BD1MXhtFent7rL&md5=98e0753e3aaf159deaa2fbcb378eb47dCAS | 19479991PubMed | open url image1

Marín Bivens, C. L., Grøndahl, C., Murray, A., Blume, T., Su, Y. Q., and Eppig, J. J. (2004). Meiosis-activating sterol promotes the metaphase I to metaphase II transition and preimplantation developmental competence of mouse oocytes maturing in vitro. Biol. Reprod. 70, 1458–1464.
Meiosis-activating sterol promotes the metaphase I to metaphase II transition and preimplantation developmental competence of mouse oocytes maturing in vitro.CrossRef | 14736819PubMed | open url image1

Moawad, A. R., Tan, S. L., Xu, B., Chen, H. Y., and Taketo, T. (2013). L-carnitine supplementation during vitrification of mouse oocytes at the germinal vesicle stage improves preimplantation development following maturation and fertilization in vitro. Biol. Reprod. 88, 104.
L-carnitine supplementation during vitrification of mouse oocytes at the germinal vesicle stage improves preimplantation development following maturation and fertilization in vitro.CrossRef | 23446455PubMed | open url image1

Nagaoka, S. I., Hassold, T. J., and Hunt, P. A. (2012). Human aneuploidy: mechanisms and new insights into an age-old problem. Nat. Rev. Genet. 13, 493–504.
Human aneuploidy: mechanisms and new insights into an age-old problem.CrossRef | 1:CAS:528:DC%2BC38Xos12ht78%3D&md5=172d8e6f306de2f2afaf0e74c384ce65CAS | 22705668PubMed | open url image1

Nishimura, K., Shiina, R., Kashiwagi, K., and Igarashi, K. (2006). Decrease in polyamines with aging and their ingestion from food and drink. J. Biochem. 139, 81–90.
Decrease in polyamines with aging and their ingestion from food and drink.CrossRef | 1:CAS:528:DC%2BD28XislSrsbc%3D&md5=78df1fa2676e4584eeb7c9fef8c1a48aCAS | 16428322PubMed | open url image1

Nybo Andersen, A. M., Wohlfahrt, J., Christens, P., Olsen, J., and Melbye, M. (2000). Maternal age and fetal loss: population based register linkage study. BMJ 320, 1708–1712.
Maternal age and fetal loss: population based register linkage study.CrossRef | 1:STN:280:DC%2BD3czitlSmug%3D%3D&md5=9d80cdfad89083c7f8888e607c7de66eCAS | 10864550PubMed | open url image1

Paria, B. C., and Dey, S. K. (1990). Preimplantation embryo development in vitro: cooperative interactions among embryos and role of growth factors. Proc. Natl. Acad. Sci. USA 87, 4756–4760.
Preimplantation embryo development in vitro: cooperative interactions among embryos and role of growth factors.CrossRef | 1:CAS:528:DyaK3cXkslWrsbw%3D&md5=dc62a3cd817cbec57c6630c0b81219d7CAS | 2352946PubMed | open url image1

Pendeville, H., Carpino, N., Marine, J. C., Takahashi, Y., Muller, M., Martial, J. A., and Cleveland, J. L. (2001). The ornithine decarboxylase gene is essential for cell survival during early murine development. Mol. Cell. Biol. 21, 6549–6558.
The ornithine decarboxylase gene is essential for cell survival during early murine development.CrossRef | 1:CAS:528:DC%2BD3MXmvFGhsbw%3D&md5=40ad5a820aab63163bcc9db66500bf51CAS | 11533243PubMed | open url image1

Persson, L., Isaksson, K., Rosengren, E., and Sundler, F. (1986). Distribution of ornithine decarboxylase in ovaries of rat and hamster during pro-oestrus. Acta Endocrinol. (Copenh.) 113, 403–409.
| 1:CAS:528:DyaL2sXjtl2m&md5=e9e6ed9bd77aecb3c909ee4748cd09f9CAS | 3538740PubMed | open url image1

Pohjanpelto, P. (1975). Putrescine shortens the S-period in human fibroblasts. Biomedicine Paris 23, 350–352.
| 1:CAS:528:DyaE28XhtF2jur4%3D&md5=9b145f7ef5f6e792462c3a31c99afd80CAS | open url image1

Rehman, K. S., Bukulmez, O., Langley, M., Carr, B. R., Nackley, A. C., Doody, K. M., and Doody, K. J. (2007). Late stages of embryo progression are a much better predictor of clinical pregnancy than early cleavage in intracytoplasmic sperm injection and in vitro fertilization cycles with blastocyst-stage transfer. Fertil. Steril. 87, 1041–1052.
Late stages of embryo progression are a much better predictor of clinical pregnancy than early cleavage in intracytoplasmic sperm injection and in vitro fertilization cycles with blastocyst-stage transfer.CrossRef | 17336973PubMed | open url image1

Sakkas, D., Lane, M., and Gardner, D. K. (2004). Assessment of preimplantation embryo development and viability. In ‘A Laboratory Guide to the Mammalian Embryo’. (Eds D. K. Gardner, M. Lane and A. J. Watson.) pp. 66–8. (Oxford University Press: Oxford.)

Santos Filho, E., Noble, J. A., Poli, M., Griffiths, T., Emerson, G., and Wells, D. (2012). A method for semi-automatic grading of human blastocyst microscope images. Hum. Reprod. 27, 2641–2648.
A method for semi-automatic grading of human blastocyst microscope images.CrossRef | 1:STN:280:DC%2BC38jltFagtA%3D%3D&md5=54d290f25f0a3c3693c8e6cf9c1651f7CAS | 22736327PubMed | open url image1

Schieve, L. A., Tatham, L., Peterson, H. B., Toner, J., and Jeng, G. (2003). Spontaneous abortion among pregnancies conceived using assisted reproductive technology in the United States. Obstet. Gynecol. 101, 959–967.
| 12738158PubMed | open url image1

Smitz, J. E., Thompson, J. G., and Gilchrist, R. B. (2011). The promise of in vitro maturation in assisted reproduction and fertility preservation. Semin. Reprod. Med. 29, 24–37.
The promise of in vitro maturation in assisted reproduction and fertility preservation.CrossRef | 1:CAS:528:DC%2BC3MXhvVGitrg%3D&md5=eb680c125fcfc2a3c3dd8300177eb0e0CAS | 21207332PubMed | open url image1

Summers, M. C., McGinnis, L. K., Lawitts, J. A., Raffin, M., and Biggers, J. D. (2000). IVF of mouse ova in a simplex optimized medium supplemented with amino acids. Hum. Reprod. 15, 1791–1801.
IVF of mouse ova in a simplex optimized medium supplemented with amino acids.CrossRef | 1:CAS:528:DC%2BD3cXmtFOnsrc%3D&md5=d652d2723236a4a5c2bf0d67a05e6fdaCAS | 10920105PubMed | open url image1

Talbert, G. B. (1971). Effect of maternal age on postimplantation reproductive failure in mice. J. Reprod. Fertil. 24, 449–452.
Effect of maternal age on postimplantation reproductive failure in mice.CrossRef | 1:STN:280:DyaE3M7jvVOmug%3D%3D&md5=c71a5ce8ca8c4ec882132f40afd7e74fCAS | 5102250PubMed | open url image1

Tao, Y., and Liu, X. J. (2013). Deficiency of ovarian ornithine decarboxylase contributes to aging-related egg aneuploidy in mice. Aging Cell 12, 42–49.
Deficiency of ovarian ornithine decarboxylase contributes to aging-related egg aneuploidy in mice.CrossRef | 1:CAS:528:DC%2BC3sXjt1Wnsrc%3D&md5=1ada0871fc3582bfb7afadae5ec5c08fCAS | 23061827PubMed | open url image1

Tao, Y., and Liu, X. J. (2015). The majority of resorptions in old mice are euploid. PLoS One 10, e0143360.
The majority of resorptions in old mice are euploid.CrossRef | 26636341PubMed | open url image1

Tao, Y., Liu, D., Mo, G., Wang, H., and Liu, X. J. (2015). Peri-ovulatory putrescine supplementation reduces embryo resorption in older mice. Hum. Reprod. 30, 1867–1875.
Peri-ovulatory putrescine supplementation reduces embryo resorption in older mice.CrossRef | 26082481PubMed | open url image1

Til, H. P., Falke, H. E., Prinsen, M. K., and Willems, M. I. (1997). Acute and subacute toxicity of tyramine, spermidine, spermine, putrescine and cadaverine in rats. Food Chem. Toxicol. 35, 337–348.
Acute and subacute toxicity of tyramine, spermidine, spermine, putrescine and cadaverine in rats.CrossRef | 1:CAS:528:DyaK2sXktlyrt7w%3D&md5=a0b3180ea74a0bad2e51bdd190760507CAS | 9207896PubMed | open url image1

Veldhuis, J. D., and Hammond, J. M. (1979). Role of ornithine decarboxylase in granulosa-cell replication and steroidogenesis in vitro. Biochem. Biophys. Res. Commun. 91, 770–777.
Role of ornithine decarboxylase in granulosa-cell replication and steroidogenesis in vitro.CrossRef | 1:CAS:528:DyaL3cXlsFOgsg%3D%3D&md5=2e4b102813143d7a35e948db817d3600CAS | 526280PubMed | open url image1

Wale, P. L., and Gardner, D. K. (2016). The effects of chemical and physical factors on mammalian embryo culture and their importance for the practice of assisted human reproduction. Hum. Reprod. Update 22, 2–22.
The effects of chemical and physical factors on mammalian embryo culture and their importance for the practice of assisted human reproduction.CrossRef | 26207016PubMed | open url image1

Washkowitz, A. J., Schall, C., Zhang, K., Wurst, W., Floss, T., Mager, J., and Papaioannou, V. E. (2015). Mga is essential for the survival of pluripotent cells during peri-implantation development. Development 142, 31–40.
Mga is essential for the survival of pluripotent cells during peri-implantation development.CrossRef | 1:CAS:528:DC%2BC2MXkt1Whs70%3D&md5=791968b7418c93e663f31e21370cd678CAS | 25516968PubMed | open url image1

Zhang, H., Liu, L., Li, X., Busayavalasa, K., Shen, Y., Hovatta, O., Gustafsson, J. A., and Liu, K. (2014). Life-long in vivo cell-lineage tracing shows that no oogenesis originates from putative germline stem cells in adult mice. Proc. Natl. Acad. Sci. USA 111, 17983–17988.
Life-long in vivo cell-lineage tracing shows that no oogenesis originates from putative germline stem cells in adult mice.CrossRef | 1:CAS:528:DC%2BC2cXitVSitb3K&md5=ef2c7f9eaa142a4524111b86d70e041dCAS | 25453063PubMed | open url image1



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