Dose-dependent effects of gonadotropin on oocyte developmental competence and apoptosis
Shan Liu A B C D , Huai L. Feng A D E , Dennis Marchesi A , Zi-Jiang Chen B C E and Avner Hershlag A
+ Author Affiliations
- Author Affiliations
A Center for Human Reproduction, North Shore–Long Island Jewish Health System, New York University School of Medicine, Manhasset, NY 11030, USA.
B National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong Province, Jinan 250021, China.
C Key Laboratory for Reproductive Endocrinology of Ministry of Education Center for Reproductive Medicine, Provincial Hospital Affiliated to Shandong University, Shandong Province, Jinan 250021, China.
D These authors contributed equally to this paper.
E Corresponding authors. Emails: HFeng@NSHS.edu; chenzijiang@hotmail.com
Reproduction, Fertility and Development 23(8) 990-996 https://doi.org/10.1071/RD11079
Submitted: 23 April 210 Accepted: 3 May 2011 Published: 22 September 2011
Abstract
The aim of the present study was to evaluate the effect of gonadotropins (Gn) on oocyte maturation, developmental competence and apoptosis in an animal model. Bovine cumulus–oocyte complexes (COCs) were matured for 24 h in media supplemented with varying concentrations of Bravelle (B), B + Menopur (B + M) or B + Repronex (B + R) (Ferring Pharmaceuticals, Parsiappany, NJ, USA). Then, nuclear maturation, embryo development, and apoptosis in cumulus cells and oocytes were evaluated. Low to moderate Gn concentrations (75–7500 mIU mL–1) effectively improved nuclear maturation and in vitro development. Higher concentrations of Gn (75 000 mIU mL–1) did not have any added beneficial effects and nuclear maturation and blastocyst rates in the presence of these concentrations were comparable to control (P > 0.05). Most COCs showed slight apoptosis when exposed to 75, 750 and 7500 mIU mL–1 Gn; however, when the concentration was increased to 75 000 mIU mL–1, the proportion of moderately apoptotic COCs increased. In conclusion, extremely high concentrations of Gn have detrimental effects on oocyte nuclear maturation and embryo development and increase apoptosis in cumulus cells, suggesting the importance of judicious use of Gn in assisted reproductive technologies (ART).
Additional keywords: ART, in vitro maturation, TUNEL.
References
Anguita, B., Vandaele, L., Mateusen, B., Maes, D., and Van Soom, A. (2007). Developmental competence of bovine oocytes is not related to apoptosis incidence in oocytes, cumulus cells and blastocysts. Theriogenology 67, 537–549.| Developmental competence of bovine oocytes is not related to apoptosis incidence in oocytes, cumulus cells and blastocysts.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXitlyrsQ%3D%3D&md5=b4f4c1112e2c243c4a20b12cca8dd33eCAS | 17007918PubMed |
Baart, E. B., Martini, E., Eijkemans, M. J., Van Opstal, D., Beckers, N. G., Verhoeff, A., Macklon, N. S., and Fauser, B. C. (2007). Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation embryo: a randomized controlled trial. Hum. Reprod. 22, 980–988.
| Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation embryo: a randomized controlled trial.Crossref | GoogleScholarGoogle Scholar | 17204525PubMed |
Check, J. H. (2010). Advantages of using a lower vs higher dosage of gonadotropins for follicular maturation including cycles of in vitro fertilization–embryo transfer. Clin. Exp. Obstet. Gynecol. 37, 84–88.
| 1:STN:280:DC%2BC3cbntFOmsw%3D%3D&md5=041621570f7c5fd23402b281d9946240CAS | 21077491PubMed |
Corn, C. M., Hauser-Kronberger, C., Moser, M., Tews, G., and Ebner, T. (2005). Predictive value of cumulus cell apoptosis with regard to blastocyst development of corresponding gametes. Fertil. Steril. 84, 627–633.
| Predictive value of cumulus cell apoptosis with regard to blastocyst development of corresponding gametes.Crossref | GoogleScholarGoogle Scholar | 16169395PubMed |
Eppig, J. J. (1991). Intercommunication between mammalian oocytes and companion somatic cells. Bioessays 13, 569–574.
| Intercommunication between mammalian oocytes and companion somatic cells.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK387is1ShsA%3D%3D&md5=f4e8818ddf8ca51796a545b119b3f763CAS | 1772412PubMed |
Eppig, J. J., Ward-Bailey, P. F., and Coleman, D. L. (1985). Hypoxanthine and adenosine in murine ovarian follicular fluid: Concentrations and activity in maintaining oocyte meiotic arrest. Biol. Reprod. 33, 1041–1049.
| Hypoxanthine and adenosine in murine ovarian follicular fluid: Concentrations and activity in maintaining oocyte meiotic arrest.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL28XkvFartQ%3D%3D&md5=1ad3eaf8a4ed2e29b8e87459b3e708bdCAS | 4074802PubMed |
Exley, G. E., Tang, C., McElhinny, A. S., and Warner, C. M. (1999). Expression of caspase and BCL-2 apoptotic family members in mouse preimplantation embryos. Biol. Reprod. 61, 231–239.
| Expression of caspase and BCL-2 apoptotic family members in mouse preimplantation embryos.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXktFKgu7g%3D&md5=1bb6830aca61bc241be6299d1ba200a5CAS | 10377054PubMed |
Hashimoto, S., Saeki, K., Nagao, Y., Minami, N., Yamada, M., and Utsumi, K. (1998). Effects of cumulus cell density during in vitro maturation on the developmental competence of bovine oocytes. Theriogenology 49, 1451–1463.
| Effects of cumulus cell density during in vitro maturation on the developmental competence of bovine oocytes.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3c7ps1Gmug%3D%3D&md5=c30d45b1725aa7ad239ab2ea794b776cCAS | 10732009PubMed |
Izadyar, F., Dijkstra, G., Van Tol, H. T., Van den Eijnden-van Raaij, A. J., Van den Hurk, R., Colenbrander, B., and Bevers, M. M. (1998). Immunohistochemical localization and mRNA expression of activin, inhibin, follistatin, and activin receptor in bovine cumulus–oocyte complexes during in vitro maturation. Mol. Reprod. Dev. 49, 186–195.
| Immunohistochemical localization and mRNA expression of activin, inhibin, follistatin, and activin receptor in bovine cumulus–oocyte complexes during in vitro maturation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXjt1yjsw%3D%3D&md5=4c106b6ed9094e49783b945ee0960422CAS | 9444661PubMed |
Kumar, N. M., and Gilula, N. B. (1996). The gap junction communication channel. Cell 84, 381–388.
| The gap junction communication channel.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XhtFWqtr0%3D&md5=74f1b989ca4334e03ebdc001f1e04dd7CAS | 8608591PubMed |
Lee, K. S., Joo, B. S., Na, Y. J., Choi, O. H., and Kim, W. W. (2001). Cumulus cells apoptosis as an indicator to predict the quality of oocytes and the outcome of IVF-ET. J. Assist. Reprod. Genet. 18, 490–498.
| Cumulus cells apoptosis as an indicator to predict the quality of oocytes and the outcome of IVF-ET.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3MrmsVKisQ%3D%3D&md5=de48cdffea0bcf04469a6ecf60e1d79aCAS | 11665664PubMed |
Lee, S. T., Kim, T. M., Cho, M. Y., Moon, S. Y., Han, J. Y., and Lim, J. M. (2005). Development of a hamster superovulation program and adverse effects of gonadotropins on microfilament formation during oocyte development. Fertil. Steril. 83, 1264–1274.
| Development of a hamster superovulation program and adverse effects of gonadotropins on microfilament formation during oocyte development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXktFaru7w%3D&md5=dfff230c6dbd769d29d36e16516d6ff1CAS | 15831301PubMed |
Li, R., Norman, R. J., Armstrong, D. T., and Gilchrist, R. B. (2000). Oocyte-secreted factor(s) determine functional differences between bovine mural granulosa cells and cumulus cells. Biol. Reprod. 63, 839–845.
| Oocyte-secreted factor(s) determine functional differences between bovine mural granulosa cells and cumulus cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXmtFCiu7g%3D&md5=8940970846168268b51cc098c8474102CAS | 10952929PubMed |
Liu, S., Feng, H. L., Marchesi, D., Chen, Z. J., and Hershlag, A. (2011). Effect of gonadotropins on dynamic events and global deoxyribonucleic acid methylation during in vitro maturation of oocytes: an animal model. Fertil. Steril. 95, 1503–1506.e3.
| Effect of gonadotropins on dynamic events and global deoxyribonucleic acid methylation during in vitro maturation of oocytes: an animal model.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXjs1CktLo%3D&md5=131dd9b394013737ce16ce9842662911CAS | 21071022PubMed |
Mattioli, M., and Barboni, B. (2000). Signal transduction mechanism for LH in the cumulus–oocyte complex. Mol. Cell. Endocrinol. 161, 19–23.
| Signal transduction mechanism for LH in the cumulus–oocyte complex.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXisFGnuro%3D&md5=e5c021e7998231efe5b861534f6ded0aCAS | 10773386PubMed |
Matwee, C., Betts, D. H., and King, W. A. (2000). Apoptosis in the early bovine embryo. Zygote 8, 57–68.
| Apoptosis in the early bovine embryo.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXjvVemtLw%3D&md5=4b86240059161ca4b86fe2776175dc2bCAS | 10840875PubMed |
McKiernan, S. H., and Bavister, B. D. (1998). Gonadotrophin stimulation of donor females decreases post-implantation viability of cultured one-cell hamster embryos. Hum. Reprod. 13, 724–729.
| Gonadotrophin stimulation of donor females decreases post-implantation viability of cultured one-cell hamster embryos.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXivF2itLo%3D&md5=7add42534f9c45a608ac5039b4db0273CAS | 9572442PubMed |
Metcalfe, A. D., Hunter, H. R., Bloor, D. J., Lieberman, B. A., Picton, H. M., Leese, H. J., Kimber, S. J., and Brison, D. R. (2004). Expression of 11 members of the BCL-2 family of apoptosis regulatory molecules during human preimplantation embryo development and fragmentation. Mol. Reprod. Dev. 68, 35–50.
| Expression of 11 members of the BCL-2 family of apoptosis regulatory molecules during human preimplantation embryo development and fragmentation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXivFyku7k%3D&md5=0d7b51488308d20e52310dab7ca6aa9bCAS | 15039946PubMed |
Munne, S., Magli, C., Adler, A., Wright, G., de Boer, K., Mortimer, D., Tucker, M., Cohen, J., and Gianaroli, L. (1997). Treatment-related chromosome abnormalities in human embryos. Hum. Reprod. 12, 780–784.
| Treatment-related chromosome abnormalities in human embryos.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2szgtlSisw%3D%3D&md5=e213b67d1abd7374af3141fbd4202d2eCAS | 9159442PubMed |
Nakahara, K., Saito, H., Saito, T., Ito, M., Ohta, N., Takahashi, T., and Hiroi, M. (1997). The incidence of apoptotic bodies in membrana granulosa can predict prognosis of ova from patients participating in in vitro fertilization programs. Fertil. Steril. 68, 312–317.
| The incidence of apoptotic bodies in membrana granulosa can predict prognosis of ova from patients participating in in vitro fertilization programs.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2szosVGqtg%3D%3D&md5=135483d141330621a6c19dd0ad011e2bCAS | 9240262PubMed |
Roberts, R., Iatropoulou, A., Ciantar, D., Stark, J., Becker, D. L., Franks, S., and Hardy, K. (2005). Follicle-stimulating hormone affects metaphase I chromosome alignment and increases aneuploidy in mouse oocytes matured in vitro. Biol. Reprod. 72, 107–118.
| Follicle-stimulating hormone affects metaphase I chromosome alignment and increases aneuploidy in mouse oocytes matured in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXmtlOj&md5=b4c37157d05542968b2337330e3846c4CAS | 15371272PubMed |
Sidis, Y., Fujiwara, T., Leykin, L., Isaacson, K., Toth, T., and Schneyer, A. L. (1998). Characterization of inhibin/activin subunit, activin receptor, and follistatin messenger ribonucleic acid in human and mouse oocytes: evidence for activin’s paracrine signaling from granulosa cells to oocytes. Biol. Reprod. 59, 807–812.
| Characterization of inhibin/activin subunit, activin receptor, and follistatin messenger ribonucleic acid in human and mouse oocytes: evidence for activin’s paracrine signaling from granulosa cells to oocytes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXmsVGrsLY%3D&md5=45375290b1dfc66f34af82b62fabeedeCAS | 9746729PubMed |
Van der Auwera, I., and D’Hooghe, T. (2001). Superovulation of female mice delays embryonic and fetal development. Hum. Reprod. 16, 1237–1243.
| Superovulation of female mice delays embryonic and fetal development.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD3MzhsVWgsA%3D%3D&md5=3eb44ad9fdaf9f766f59103ffb2da6c9CAS | 11387298PubMed |
Verberg, M. F., Macklon, N. S., Nargund, G., Frydman, R., Devroey, P., Broekmans, F. J., and Fauser, B. C. (2009). Mild ovarian stimulation for IVF. Hum. Reprod. Update 15, 13–29.
| Mild ovarian stimulation for IVF.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD1M%2FjvVekuw%3D%3D&md5=590967847ea46d45c405e7ae591e35a8CAS | 19091755PubMed |
Warzych, E., Peippo, J., Szydlowski, M., and Lechniak, D. (2007). Supplements to in vitro maturation media affect the production of bovine blastocysts and their apoptotic index but not the proportions of matured and apoptotic oocytes. Anim. Reprod. Sci. 97, 334–343.
| Supplements to in vitro maturation media affect the production of bovine blastocysts and their apoptotic index but not the proportions of matured and apoptotic oocytes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xht1eqtrfP&md5=6ee3ce453146b088b48085982810371dCAS | 16504427PubMed |
Winston, R. M., and Hardy, K. (2002). Are we ignoring potential dangers of in vitro fertilization and related treatments? Nat. Cell Biol. 4, S14–S18.
| Are we ignoring potential dangers of in vitro fertilization and related treatments?Crossref | GoogleScholarGoogle Scholar | 12479609PubMed |
Xu, Y. W., Peng, Y. T., Wang, B., Zeng, Y. H., Zhuang, G. L., and Zhou, C. Q. (2011). High follicle-stimulating hormone increases aneuploidy in human oocytes matured in vitro. Fertil. Steril. 95, 99–104.
| High follicle-stimulating hormone increases aneuploidy in human oocytes matured in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhsFymsrvN&md5=df441ab24413af784dcebe54ad21566eCAS | 20553786PubMed |
Yuan, Y. Q., Van Soom, A., Leroy, J. L., Dewulf, J., Van Zeveren, A., de Kruif, A., and Peelman, L. J. (2005). Apoptosis in cumulus cells, but not in oocytes, may influence bovine embryonic developmental competence. Theriogenology 63, 2147–2163.
| Apoptosis in cumulus cells, but not in oocytes, may influence bovine embryonic developmental competence.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXjtFyrtb8%3D&md5=3611efb37871862ae35178abe5756b24CAS | 15826680PubMed |
Ziebe, S., Bangsboll, S., Schmidt, K. L., Loft, A., Lindhard, A., and Nyboe Andersen, A. (2004). Embryo quality in natural versus stimulated IVF cycles. Hum. Reprod. 19, 1457–1460.
| Embryo quality in natural versus stimulated IVF cycles.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD2c3msFWktQ%3D%3D&md5=226798787166a6684a739a5b68c00a52CAS | 15105402PubMed |
