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http://dx.doi.org/10.12717/DR.2021.25.4.213

Effects of Repeated Ovarian Stimulation on Ovarian Function and Aging in Mice  

Whang, Jihye (Dept. of Bioenvironmental Technology, College of Natural Sciences, Seoul Women's University)
Ahn, Cheyoung (Dept. of Bioenvironmental Technology, College of Natural Sciences, Seoul Women's University)
Kim, Soohyun (Dept. of Bioenvironmental Technology, College of Natural Sciences, Seoul Women's University)
Seok, Eunji (Dept. of Bioenvironmental Technology, College of Natural Sciences, Seoul Women's University)
Yang, Yunjeong (Dept. of Bioenvironmental Technology, College of Natural Sciences, Seoul Women's University)
Han, Goeun (Dept. of Bioenvironmental Technology, College of Natural Sciences, Seoul Women's University)
Jo, Haeun (Dept. of Bioenvironmental Technology, College of Natural Sciences, Seoul Women's University)
Yang, Hyunwon (Dept. of Bioenvironmental Technology, College of Natural Sciences, Seoul Women's University)
Publication Information
Development and Reproduction / v.25, no.4, 2021 , pp. 213-223 More about this Journal
Abstract
Controlled ovarian hyperstimulation (COH) is routinely used in the in vitro fertilization and embryo transfer (IVF-ET) cycles to increase the number of retrieved mature oocytes. However, the relationship between repeated COH and ovarian function is still controversial. Therefore, we investigated whether repeated ovarian stimulation affects ovarian aging and function, including follicular development, autophagy, and apoptosis in follicles. Ovarian hyperstimulation in mice was induced by intraperitoneal injection with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG). Mice subjected to ovarian stimulation once were used as a control group and 10 times as an experimental group. Repeated injections with PMSG and hCG significantly reduced the number of primary follicles compared to a single injection. The number of secondary and antral follicles increased slightly, while the number of corpus luteum increased significantly with repeated injections. On the other hand, repeated injections did not affect apoptosis in follicles associated with follicular atresia. The expression of autophagy-related genes Atg5, Atg12, LC3B, and Beclin1, cell proliferation-related genes mTOR, apoptosis-related genes Fas, and FasL was not significantly different between the two groups. In addition, the expression of the aging-related genes Dnmt1, Dnmt3a, and AMH were also not significantly different. In this study, we demonstrated that repeated ovarian stimulation in mice affects follicular development, but not autophagy, apoptosis, aging in ovary. These results suggest that repetition of COH in the IVF-ET cycle may not result in ovarian aging, such as a decrease in ovarian reserve in adult women.
Keywords
Apoptosis; Autophagy; In vitro fertilization and embryo transfer (IVF-ET); Ovarian function; Repeated ovarian stimulation;
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1 Hansen KR, Knowlton NS, Thyer AC, Charleston JS, Soules MR, Klein NA (2008) A new model of reproductive aging: The decline in ovarian non-growing follicle number from birth to menopause. Hum Reprod 23:699-708.   DOI
2 Leopardo NP, Velazquez ME, Cortasa S, Gonzalez CR, Vitullo AD (2020) A dual death/survival role of autophagy in the adult ovary of Lagostomus maximus (Mammalia-Rodentia). PLOS ONE 15:e0232819.   DOI
3 Li P, Zhu H, Tan L, Zhao D, Ma L, Xiang Y, Zhang D, Dou Q, Lu N (2015) Effects of high progesterone on outcomes of in vitro fertilization-embryo transfer in patients with different ovarian responses. Syst Biol Reprod Med 61:161-167.   DOI
4 Nie X, Dai Y, Zheng Y, Bao D, Chen Q, Yin Y, Fu H, Hou D (2018) Establishment of a mouse model of premature ovarian failure using consecutive superovulation. Cell Physiol Biochem 51:2341-2358.   DOI
5 Kaufmann T, Strasser A, Jost PJ (2012) Fas death receptor signalling: Roles of Bid and XIAP. Cell Death Differ 19:42-50.   DOI
6 Castedo M, Ferri KF, Kroemer G (2002) Mammalian target of rapamycin (mTOR): Pro- and anti-apoptotic. Cell Death Differ 9:99-100.   DOI
7 Chari T, Griswold S, Andrews NA, Fagiolini M (2020) The stage of the estrus cycle is critical for interpretation of female mouse social interaction behavior. Front Behav Neurosci 14:113.
8 Griesinger G (2010) Ovarian hyperstimulation syndrome prevention strategies: Use of gonadotropin-releasing hormone antagonists. Semin Reprod Med 28:493-499.   DOI
9 Li Q, Cai M, Wang J, Gao Q, Guo X, Jia X, Xu S, Zhu H (2020) Decreased ovarian function and autophagy gene methylation in aging rats. J Ovarian Res 13:12.   DOI
10 Zou Z, Tao T, Li H, Zhu X (2020) mTOR signaling pathway and mTOR inhibitors in cancer: Progress and challenges. Cell Biosci 10:31.   DOI
11 Yan P, Xu J, Zeng Y, Dong G, Cao H, Zheng M, Zhu H (2017) Long-term effects of repeated superovulation on the uterus and mammary gland in rhesus monkeys. J Assist Reprod Genet 34:535-545.   DOI
12 Nagata S (1998) Fas-induced apoptosis. Intern Med 37:179-181.   DOI
13 Santos MA, Kuijk EW, Macklon NS (2010) The impact of ovarian stimulation for IVF on the developing embryo. Reproduction 139:23-34.   DOI
14 Wang Z, Tamura K, Yoshie M, Tamura H, Imakawa K, Kogo H (2003) Prostaglandin F2α-induced functional regression of the corpus luteum and apoptosis in rodents. J Pharmacol Sci 92:19-27.   DOI
15 Yu YS, Sui HS, Han ZB, Li W, Luo MJ, Tan JH (2004) Apoptosis in granulosa cells during follicular atresia: Relationship with steroids and insulin-like growth factors. Cell Res 14:341-346.   DOI
16 Acevedo B, Gomez-Palomares JL, Ricciarelli E, Hernandez ER (2006) Triggering ovulation with gonadotropin-releasing hormone agonists does not compromise embryo implantation rates. Fertil Steril 86:1682-1687.   DOI
17 Baker TG (1963) A quantitative and cytological study of germ cells in human ovaries. Proc R Soc Lond B Biol Sci 158:417-433.   DOI
18 Caligara C, Navarro J, Vargas G, Simon C, Pellicer A, Remohi J (2001) The effect of repeated controlled ovarian stimulation in donors. Hum Reprod 16:2320-2323.   DOI
19 Chaffin CL, Stouffer RL (2000) Role of gonadotrophins and progesterone in the regulation of morphological remodelling and atresia in the monkey peri-ovulatory follicle. Hum Reprod 15:2489-2495.   DOI
20 Antonouli S, Palmerini MG, Bianchi S, Rossi G, Cecconi S, Belli M, Bernardi S, Khalili MA, Familiari G, Nottola SA, Macchiarelli G (2020) Repeated hyperstimulation affects the ultrastructure of mouse fallopian tube epithelium. J Reprod Dev 66:387-397.   DOI
21 Macklon NS, Stouffer RL, Giudice LC, Fauser BCJM (2006) The science behind 25 years of ovarian stimulation for in vitro fertilization. Endocr Rev 27:170-207.   DOI
22 Christenson LK, Stouffer RL (1997) Follicle-stimulating hormone and luteinizing hormone/chorionic gonadotropin stimulation of vascular endothelial growth factor production by macaque granulosa cells from pre- and periovulatory follicles. J Clin Endocrinol Metab 82:2135-2142.   DOI
23 Dong G, Guo Y, Cao H, Zhou T, Zhou Z, Sha J, Guo X, Zhu H (2014) Long-term effects of repeated superovulation on ovarian structure and function in rhesus monkeys. Fertil Steril 102:1452-1457.   DOI
24 Xi X, Zou Q, Wei Y, Chen Y, Wang X, Lv D, Li P, Wen A, Zhu L, Tang G, Ma J, Li M, Jiang Y (2019) Dynamic changes of DNA methylation and transcriptome expression in porcine ovaries during aging. BioMed Res Int 2019:8732023.
25 Chao HT, Lee SY, Lee HM, Liao TL, Wei YH, Kao SH (2005) Repeated ovarian stimulations induce oxidative damage and mitochondrial DNA mutations in mouse ovaries. Ann NY Acad Sci 1042:148-156.   DOI
26 Jacobs HS, Agrawal R (1998) 4 Complications of ovarian stimulation. Baillieres Clin Obstet Gynaecol 12:565-579.   DOI