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

Distribution pattern of cytoplasmic organelles, spindle integrity, oxidative stress, octamer-binding transcription factor 4 (Oct4) expression and developmental potential of oocytes following multiple superovulation

Guruprasad Kalthur A E , Sujith Raj Salian A , Ramya Nair A , Jemey Mathew A , Satish Kumar Adiga A , Sneha Guruprasad Kalthur B , Dimphy Zeegers C and M. Prakash Hande C D
+ Author Affiliations
- Author Affiliations

A Division of Clinical Embryology, Department of Obstetrics and Gynecology, Kasturba Medical College, Manipal University, Manipal, 576104, India.

B Department of Anatomy, Kasturba Medical College, Manipal University, Manipal, 576104, India.

C Genome Stability Laboratory, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117597, Singapore.

D Tembusu College, National University of Singapore, 138598, Singapore.

E Corresponding author. Email: guru.kalthur@manipal.edu

Reproduction, Fertility and Development 28(12) 2027-2038 https://doi.org/10.1071/RD15184
Submitted: 9 May 2015  Accepted: 9 June 2015   Published: 15 July 2015

Abstract

The aim of the present study was to determine the effects of repeated superovulation on oocyte quality and embryo developmental potential. Female Swiss albino mice were injected with 5 IU pregnant mare’s serum gonadotropin followed 48 h by 10 IU human chorionic gonadotropin. Mice were superovulated up to four times with a gap of 7 days between each superovulation cycle. Ovarian weight increased significantly with an increasing number of superovulation cycles. Although the first stimulation cycle resulted in a threefold increase in the number of oocytes, the number of oocytes decreased gradually after subsequent stimulations. Increased cytoplasmic fragmentation, abnormal mitochondrial distribution, aggregation of Golgi apparatus, spindle damage, increased intracellular oxidative stress and a decrease in expression of octamer-binding transcription factor 4 (Oct4) expression were observed in these oocytes. Further, embryos derived from mice subjected to multiple stimulation cycles exhibited a low blastocyst rate, decreased hatching rate and increased apoptosis in blastocysts. In conclusion, the present study demonstrates that repeated superovulation adversely affects mouse oocyte quality by altering the distribution of cytoplasmic organelles, increasing oxidative stress and decreasing Oct4 expression, resulting in poor developmental potential of the embryos.

Additional keywords: embryo development, endoplasmic reticulum, Golgi apparatus, mitochondria, reactive oxygen species, spindle damage.


References

Bavister, B. D., Dees, C., and Schultz, R. D. (1986). Refractoriness of rhesus monkeys to repeated ovarian stimulation by exogenous gonadotropins is caused by nonprecipitating antibodies. Am. J. Reprod. Immunol. Microbiol. 11, 11–16.
| 1:CAS:528:DyaL28XltVyku78%3D&md5=cb971976d630d2302be6a8d1b75f45eaCAS | 3740345PubMed |

Buxton, C. L., and Herrmann, W. (1960). Induction of ovulation in the human with human gonadotropins. Yale J. Biol. Med. 33, 145–147.
| 1:STN:280:DyaF3c%2FgvVOmsw%3D%3D&md5=7ceca968e56500dc9fe6a916713163cfCAS | 13689504PubMed |

Caligara, C., Navarro, J., Vargas, G., Simón, C., Pellicer, A., and Remohí, J. (2001). The effect of repeated controlled ovarian stimulation in donors. Hum. Reprod. 16, 2320–2323.
The effect of repeated controlled ovarian stimulation in donors.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3Mrnt1ShsA%3D%3D&md5=da1c1514439f7b863315139e7112c7c5CAS | 11679512PubMed |

Chao, H. T., Lee, S. Y., Lee, H. M., Liao, T. L., Wei, Y. H., and Kao, S. H. (2005). Repeated ovarian stimulations induce oxidative damage and mitochondrial DNA mutations in mouse ovaries. Ann. N. Y. Acad. Sci. 1042, 148–156.
Repeated ovarian stimulations induce oxidative damage and mitochondrial DNA mutations in mouse ovaries.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXot1Cqsbs%3D&md5=1f05c0080bab1c1c043400b3aaa726e4CAS | 15965057PubMed |

Combelles, C. M., and Albertini, D. F. (2003). Assessment of oocyte quality following repeated gonadotropin stimulation in the mouse. Biol. Reprod. 68, 812–821.
Assessment of oocyte quality following repeated gonadotropin stimulation in the mouse.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXhsFGlu7o%3D&md5=cd4ed7979ee99445a2229b1881f023a3CAS | 12604630PubMed |

Coticchio, G., Albertini, D. F., and Santis, L. D. (2012). ‘Oogenesis.’ (Springer-Verlag: London.)

Diamond, M. P., DeCherney, A. H., Hill, G. A., Nero, F., and Wentz, A. C. (1987). Response to repetitive cycles of ovulation induction in the same women. J. In Vitro Fert. Embryo Transf. 4, 251–255.
Response to repetitive cycles of ovulation induction in the same women.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL1c%2FovFWkuw%3D%3D&md5=733c33f016c2c73d293608ddb0b2b99cCAS | 3694005PubMed |

Dong, G., Guo, Y., Cao, H., Zhou, T., Zhou, Z., Sha, J., Guo, X., and Zhu, H. (2014). Long-term effectsof repeated superovulation on ovarian structure and function in rhesus monkeys. Fertil. Steril. 102, 1452–1457.e1.
Long-term effectsof repeated superovulation on ovarian structure and function in rhesus monkeys.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhvVOku77O&md5=51ad65096d7c47990ca32dbc269e4799CAS | 25217873PubMed |

Eichenlaub-Ritter, U., Chandley, A. C., and Gosden, R. G. (1986). Alterations to the microtubular cytoskeleton and increased disorder of chromosome alignment in spontaneously ovulated mouse oocytes aged in vivo: an immunofluorescence study. Chromosoma 94, 337–345.
Alterations to the microtubular cytoskeleton and increased disorder of chromosome alignment in spontaneously ovulated mouse oocytes aged in vivo: an immunofluorescence study.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL2s7mtFWitw%3D%3D&md5=6fa3e546fed3dc45fa8b2798d5903936CAS | 3549193PubMed |

Felty, Q., Xiong, W. C., Sun, D., Sarkar, S., Singh, K. P., Parkash, J., and Roy, D. (2005). Estrogen-induced mitochondrial reactive oxygen species as signal-transducing messengers. Biochemistry 44, 6900–6909.
Estrogen-induced mitochondrial reactive oxygen species as signal-transducing messengers.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXjtFart7g%3D&md5=cc13266718c5d92cf73c290375b557e0CAS | 15865435PubMed |

Fowler, R. E., and Edwards, R. G. (1957). Induction of superovulation and pregnancy in mature mice by gonadotrophins. J. Endocrinol. 15, 374–384.
Induction of superovulation and pregnancy in mature mice by gonadotrophins.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaG2sXhtVSmsLc%3D&md5=bd235ee47fd4b9ea86697b8d71da5149CAS | 13475597PubMed |

Guérin, P., El Mouatassim, S., and Ménézo, Y. (2001). Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings. Hum. Reprod. Update 7, 175–189.
Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings.Crossref | GoogleScholarGoogle Scholar | 11284661PubMed |

Guzick, D. S., Wilkes, C., and Jones, H. W. (1986). Cumulative pregnancy rates for in vitro fertilization. Fertil. Steril. 46, 663–667.
| 1:STN:280:DyaL2s%2FgsFertw%3D%3D&md5=d186cd3b4a2ceeb7586b3c078387fcf1CAS | 3758386PubMed |

Haan, G., Bernardus, R. E., Hollanders, J. M., Leerentveld, R. A., Prak, F. M., and Naaktgeboren, N. (1991). Results of IVF from a prospective multicentre study. Hum. Reprod. 6, 805–810.
| 1:STN:280:DyaK38%2FpvVKmtQ%3D%3D&md5=bc2d5ba4dad97568fd343c521ebcd917CAS | 1757518PubMed |

Hashimoto, S., Minami, N., Yamada, M., and Imai, H. (2000). Excessive concentration of glucose during in vitro maturation impairs the developmental competence of bovine oocytes after in vitro fertilization: relevance to intracellular reactive oxygen species and glutathione contents. Mol. Reprod. Dev. 56, 520–526.
Excessive concentration of glucose during in vitro maturation impairs the developmental competence of bovine oocytes after in vitro fertilization: relevance to intracellular reactive oxygen species and glutathione contents.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXkslKlur8%3D&md5=cdf8c1adee0df2bf60b6dcb04372f90eCAS | 10911402PubMed |

Heggeness, M. H., Simon, M., and Singer, S. J. (1978). Association of mitochondria with microtubules in cultured cells. Proc. Natl Acad. Sci. USA 75, 3863–3866.
Association of mitochondria with microtubules in cultured cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE1cXlvFClt7w%3D&md5=48c6d12ac8ea9e8706cdd8c55289d4feCAS |

Hershlag, A., Kaplan, E. H., Loy, R. A., DeCherney, A. H., and Lavy, G. (1991). Heterogeneity in patient populations explains differences in in vitro fertilization programs. Fertil. Steril. 56, 913–917.
| 1:STN:280:DyaK38%2FjvVWiuw%3D%3D&md5=4405e6b6b68fed9ca719970b54aaf9bbCAS | 1936326PubMed |

Igarashi, M., and Matsumoto, S. (1957). Induction of human ovulation by individualized gonadotrophin therapy in two phases. Am. J. Obstet. Gynecol. 73, 1294–1298.
| 1:STN:280:DyaG2s%2FntFWltQ%3D%3D&md5=b8102e212dc46e96955cf0aae53fe0edCAS | 13424594PubMed |

Johnson, L. V., Walsh, M. L., and Chen, L. B. (1980). Localization of mitochondria in living cells with rhodamine 123. Proc. Natl Acad. Sci. USA 77, 990–994.
Localization of mitochondria in living cells with rhodamine 123.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL3cXhslKqtbw%3D&md5=014d0a6c9dc67f357b81fed349cee8c5CAS | 6965798PubMed |

Joo, B. S., Park, S. H., An, B. M., Kim, K. S., Moon, S. E., and Moon, H. S. (2010). Serum estradiol levels during controlled ovarian hyperstimulation influence the pregnancy outcome of in vitro fertilization in a concentration-dependent manner. Fertil. Steril. 93, 442–446.
Serum estradiol levels during controlled ovarian hyperstimulation influence the pregnancy outcome of in vitro fertilization in a concentration-dependent manner.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXjsFyktLc%3D&md5=2041b0b292789a74d33ca19fa1f5a97dCAS | 19394001PubMed |

Kanayama, K., and Osada, H. (2000). The yield of abnormal unfertilized eggs observed after repeated gonadotrophin-induced ovulation. J. Int. Med. Res. 28, 24–27.
The yield of abnormal unfertilized eggs observed after repeated gonadotrophin-induced ovulation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXjsVektr0%3D&md5=15169a0ebdf2313713c1f7a217baca6fCAS | 10815644PubMed |

Li, L., Baibakov, B., and Dean, J. (2008). A subcortical maternal complex essential for preimplantation mouse embryogenesis. Dev. Cell 15, 416–425.
A subcortical maternal complex essential for preimplantation mouse embryogenesis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtFOit7vL&md5=87994387cce2a383b8b259408e0fb0b2CAS | 18804437PubMed |

Liehr, J. G., Ulubelen, A. A., and Strobel, H. W. (1986). Cytochrome P-450-mediated redox cycling of estrogens. J. Biol. Chem. 261, 16 865–16 870.
| 1:CAS:528:DyaL2sXps1elsQ%3D%3D&md5=8ef023b616c9614cff063ff1e9d890b5CAS |

Lin, T. P., and Bailey, D. W. (1965). Difference between two inbred strains of mice in ovulatory response to repeated administration of gonadotrophins. J. Reprod. Fertil. 10, 253–259.
Difference between two inbred strains of mice in ovulatory response to repeated administration of gonadotrophins.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaF28Xht1yjsA%3D%3D&md5=4d572bec9b70e784243f8d8f90a929ccCAS | 5836272PubMed |

Liu, S., Li, Y., Gao, X., Yan, J. H., and Chen, Z. J. (2010). Changes in the distribution of mitochondria before and after in vitro maturation of human oocytes and the effect of in vitro maturation on mitochondria distribution. Fertil. Steril. 93, 1550–1555.
Changes in the distribution of mitochondria before and after in vitro maturation of human oocytes and the effect of in vitro maturation on mitochondria distribution.Crossref | GoogleScholarGoogle Scholar | 19423101PubMed |

Meldrum, D. R., Silverberg, K. M., Bustillo, M., and Stokes, L. (1998). Success rate with repeated cycles of in vitro fertilization–embryo transfer. Fertil. Steril. 69, 1005–1009.
Success rate with repeated cycles of in vitro fertilization–embryo transfer.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1c3ovV2ksQ%3D%3D&md5=58a8b4c22fea154635eff3f658623bbcCAS | 9627284PubMed |

Motta, P. M., Nottola, S. A., Makabe, S., and Heyn, R. (2000). Mitochondrial morphology in human fetal and adult female germ cells. Hum. Reprod. 15, 129–147.
Mitochondrial morphology in human fetal and adult female germ cells.Crossref | GoogleScholarGoogle Scholar | 11041520PubMed |

Nair, R., Singh, V. J., Salian, S. R., Kalthur, S. G., D’Souza, A. S., Shetty, P. K., Mutalik, S., Kalthur, G., and Adiga, S. K. (2014). Methyl parathion inhibits the nuclear maturation, decreases the cytoplasmic quality in oocytes and alters the developmental potential of embryos of Swiss albino mice. Toxicol. Appl. Pharmacol. 279, 338–350.
Methyl parathion inhibits the nuclear maturation, decreases the cytoplasmic quality in oocytes and alters the developmental potential of embryos of Swiss albino mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhsVGgtLnO&md5=04401aca81e90d2ffb4dfd8c8c5e8b44CAS | 25038315PubMed |

Nasr-Esfahani, M. M., and Johnson, M. H. (1991). The origin of reactive oxygen species in mouse embryos cultured in vitro. Development 113, 551–560.
| 1:CAS:528:DyaK38XhvVOqsw%3D%3D&md5=503152d6033862e4bf6fa9c9a0e7412bCAS | 1664322PubMed |

Opsahl, M. S., Blauer, K. L., Black, S. H., Dorfmann, A., Sherins, R. J., and Schulman, J. D. (2001). Pregnancy rates in sequential in vitro fertilization cycles by oocyte donors. Obstet. Gynecol. 97, 201–204.
Pregnancy rates in sequential in vitro fertilization cycles by oocyte donors.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3M7otVygtA%3D%3D&md5=3e75a8133e3ada5e56394d4d8d25675eCAS | 11165582PubMed |

Ottobre, J. S., and Stouffer, R. L. (1985). Antibody production in rhesus monkeys following prolonged administration of human chorionic gonadotropin. Fertil. Steril. 43, 122–128.
| 1:CAS:528:DyaL2MXht1Gktb0%3D&md5=a92bd012ad61e72fa48115aeaaf909c9CAS | 3917404PubMed |

Padilla, S. L., and Garcia, J. E. (1989). Effect of maternal age and number of in vitro fertilization procedureson pregnancy outcome. Fertil. Steril. 52, 270–273.
| 1:STN:280:DyaL1MzisFOisQ%3D%3D&md5=2329e862df8526fc357f2c2358fab201CAS | 2753174PubMed |

Rabinson, J., Ashkenazi, J., Homburg, R., Meltcer, S., Anteby, E. Y., and Orvieto, R. (2009). Repeated in vitro fertilization cycle attempts in patients undergoing controlled ovarianhyperstimulation with use of gonadotropin-releasing hormone antagonists. Fertil. Steril. 91, 1473–1475.
Repeated in vitro fertilization cycle attempts in patients undergoing controlled ovarianhyperstimulation with use of gonadotropin-releasing hormone antagonists.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXnsF2gu7g%3D&md5=7ca1f6b88fb814268894d073b09fd69bCAS | 18937940PubMed |

Reel, J. R., Humphrey, R. R., and Dermody, W. C. (1976). Luteinizing hormone-releasing hormone versus human chorionic gonadotropin: differential effect on the development of ovulatory refractoriness and antibodies. Fertil. Steril. 27, 59–64.
| 1:CAS:528:DyaE28XpvF2rsQ%3D%3D&md5=e7a16133c7d0865ccb645c8fb8ff2649CAS | 1107073PubMed |

Rogalski, A. A., and Singer, S. J. (1984). Associations of elements of the Golgi apparatus with microtubules. J. Cell Biol. 99, 1092–1100.
Associations of elements of the Golgi apparatus with microtubules.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2cXlsVyqurg%3D&md5=0bd0181b6db04d0a8610307427cbece2CAS | 6381504PubMed |

Sakurai, N., Fujii, T., Hashizume, T., and Sawai, K. (2013). Effects of downregulating oct-4 transcript by RNA interference on early development of porcine embryos. J. Reprod. Dev. 59, 353–360.
Effects of downregulating oct-4 transcript by RNA interference on early development of porcine embryos.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhs1SitrbI&md5=0b6af6e9b33ff786c5ce6365ec4337feCAS | 23628850PubMed |

Saunders, F. J. (1947). Induction of ovulation in the diestrous mouse by gonadotropins. Endocrinology 40, 1–8.
Induction of ovulation in the diestrous mouse by gonadotropins.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaH2s%2Fks1KmtQ%3D%3D&md5=5abd408679a0fe96d80493e4179a52b9CAS | 20285143PubMed |

Spink, D. C., Eugster, H. P., Lincoln, D. W., Schuetz, J. D., Schuetz, E. G., Johnson, J. A., Kaminsky, L. S., and Gierthy, J. F. (1992). 17 beta-estradiol hydroxylation catalyzed by human cytochrome P450 1A1: a comparison of the activities induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in MCF-7 cells with those from heterologous expression of the cDNA. Arch. Biochem. Biophys. 293, 342–348.
17 beta-estradiol hydroxylation catalyzed by human cytochrome P450 1A1: a comparison of the activities induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin in MCF-7 cells with those from heterologous expression of the cDNA.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK38XktVynsrg%3D&md5=65e89ecccea7f5fab45f25c3631fb8a5CAS | 1536570PubMed |

Stewart, L. M., Holman, C. D. J., Hart, R., Bulsara, M. K., Preen, D. B., and Finn, J. C. (2012). In vitro fertilization and breast cancer: is there cause for concern? Fertil. Steril. 98, 334–340.
In vitro fertilization and breast cancer: is there cause for concern?Crossref | GoogleScholarGoogle Scholar | 22633651PubMed |

Swanson, W. F., Roth, T. L., Graham, K., Horohov, D. W., and Godke, R. A. (1996). Kinetics of the humoral immune response to multiple treatments with exogenous gonadotropins and relation to ovarian responsiveness in domestic cats. Am. J. Vet. Res. 57, 302–307.
| 1:CAS:528:DyaK28XitVyitrY%3D&md5=c0cc10d05e5c0e89aee9bcf7855a4476CAS | 8669759PubMed |

Szołtys, M., Galas, J., Jabłonka, A., and Tabarowski, Z. (1994). Some morphological and hormonal aspects of ovulation and superovulation in the rat. J. Endocrinol. 141, 91–100.
Some morphological and hormonal aspects of ovulation and superovulation in the rat.Crossref | GoogleScholarGoogle Scholar | 8014608PubMed |

Tan, S. L., Royston, P., Campbell, S., Jacobs, H. S., Betts, J., Mason, B., and Edwards, R. G. (1992). Cumulative conception and livebirth rates after in-vitro fertilisation. Lancet 339, 1390–1394.
Cumulative conception and livebirth rates after in-vitro fertilisation.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK383osVOrtw%3D%3D&md5=28264a2eb6f856bab35d0f883ae373bbCAS | 1350813PubMed |

Terasaki, M., Chen, L. B., and Fujiwara, K. (1986). Microtubules and the endoplasmic reticulum are highly interdependent structures. J. Cell Biol. 103, 1557–1568.
Microtubules and the endoplasmic reticulum are highly interdependent structures.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL2s%2Fjtl2ntA%3D%3D&md5=6de49692a3ee85410f0f11ea25dcbbbcCAS | 3533956PubMed |

Van Blerkom, J., and Davis, P. (2001). Differential effects of repeated ovarian stimulation on cytoplasmic and spindle organization in metaphase II mouse oocytes matured in vivo and in vitro. Hum. Reprod. 16, 757–764.
Differential effects of repeated ovarian stimulation on cytoplasmic and spindle organization in metaphase II mouse oocytes matured in vivo and in vitro.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3M7ptVWlsQ%3D%3D&md5=9718c54472827e6fe81f1f53fa825ac9CAS | 11278229PubMed |

VandeVoort, C. A., and Tarantal, A. F. (2001). Recombinant human gonadotropins for macaque superovulation: repeated stimulations and post-treatment pregnancies. J. Med. Primatol. 30, 304–307.
Recombinant human gonadotropins for macaque superovulation: repeated stimulations and post-treatment pregnancies.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XitFehsbY%3D&md5=bdbfaaef2ab399598f3ba5e9cc3ea6c4CAS | 11990529PubMed |

Wehland, J., Henkart, M., Klausner, R., and Sandoval, I. V. (1983). Role of microtubules in the distribution of the Golgi apparatus: effect of taxol and microinjected anti-alpha-tubulin antibodies. Proc. Natl Acad. Sci. USA 80, 4286–4290.
Role of microtubules in the distribution of the Golgi apparatus: effect of taxol and microinjected anti-alpha-tubulin antibodies.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL3s3ntlKjtQ%3D%3D&md5=27b81c5b3a10032bf5c08f0718027d56CAS | 6136036PubMed |

Yuan, L., Dietrich, A. K., and Nardulli, A. M. (2014). 17β-Estradiol alters oxidative stress response protein expression and oxidative damage in the uterus. Mol. Cell. Endocrinol. 382, 218–226.
17β-Estradiol alters oxidative stress response protein expression and oxidative damage in the uterus.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhvFOlsrjO&md5=ae2bedecfea6ec0247d382d2a8959e6cCAS | 24103313PubMed |

Zuccotti, M., Merico, V., Redi, C. A., Bellazzi, R., Adjaye, J., and Garagna, S. (2009). Role of Oct-4 during acquisition of developmental competence in mouse oocyte. Reprod. Biomed. Online 19, 57–62.
Role of Oct-4 during acquisition of developmental competence in mouse oocyte.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtVSls7w%3D&md5=016f3860ca54e2576973d370c403a77dCAS | 20034424PubMed |

Zuccotti, M., Merico, V., Belli, M., Mulas, F., Sacchi, L., Zupan, B., Redi, C. A., Prigione, A., Adjaye, J., Bellazzi, R., and Garagna, S. (2012). OCT4 and the acquisition of oocyte developmental competence during folliculogenesis. Int. J. Dev. Biol. 56, 853–858.
OCT4 and the acquisition of oocyte developmental competence during folliculogenesis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXmvVyqsLg%3D&md5=c7f584251484c8b92b59fb69d600cfa9CAS | 23417407PubMed |