Effects of Repeated Ovarian Stimulation on Ovarian Function and Aging in Mice
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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 agingrelated 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.
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 agingrelated 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.
참고문헌 (26)
- Acevedo B, "Triggering ovulation with gonadotropin-releasing hormone agonists does not compromise embryo implantation rates", Fertil Steril, 86, pp.1682~1687 (2006)
- Antonouli S, "Repeated hyperstimulation affects the ultrastructure of mouse fallopian tube epithelium", J Reprod Dev, 66, pp.387~397 (2020)
- Baker TG, "A quantitative and cytological study of germ cells in human ovaries", Proc R Soc Lond B Biol Sci, 158, pp.417~433 (1963)
- Caligara C, "The effect of repeated controlled ovarian stimulation in donors", Hum Reprod, 16, pp.2320~2323 (2001)
- Castedo M, "Mammalian target of rapamycin(mTOR) : Pro-and antiapoptotic", Cell Death Differ, 9, pp.99~100 (2002)
- Chaffin CL, "Role of gonadotrophins and progesterone in the regulation of morphological remodelling and atresia in the monkey peri-ovulatory follicle", Hum Reprod, 15, pp.2489~2495 (2000)
- Chao HT, "Repeated ovarian stimulations induce oxidative damage and mitochondrial DNA mutations in mouse ovaries", Ann NY Acad Sci, 1042, pp.148~156 (2005)
- Chari T, "The stage of the estrus cycle is critical for interpretation of female mouse social interaction behavior", Front Behav Neurosci, 14, pp.113~ (2020)
- Christenson LK, "Follicle-stimulating hormone and luteinizing hormone", chorionic gonadotropin stimulation of vascular endothelial growth factor production by macaque granulosa cells from pre-and periovulatory follicles, 1997, pp.82, 2135~2142
- Dong G, "Long-term effects of repeated superovulation on ovarian structure and function in rhesus monkeys", Fertil Steril, 102, pp.1452~1457 (2014)
- Griesinger G, "Ovarian hyperstimulation syndrome prevention strategies : Use of gonadotropin-releasing hormone antagonists", Semin Reprod Med, 28, pp.493~499 (2010)
- Hansen KR, "A new model of reproductive aging : The decline in ovarian non-growing follicle number from birth to menopause", Hum Reprod, 23, pp.699~708 (2008)
- Jacobs HS, "4 Complications of ovarian stimulation", Baillieres Clin Obstet Gynaecol, 12, pp.565~579 (1998)
- Kaufmann T, "Fas death receptor signalling : Roles of Bid and XIAP", Cell Death Differ, 19, pp.42~50 (2012)
- Leopardo NP, "A dual death", survival role of autophagy in the adult ovary of Lagostomus maximus(Mammalia-Rodentia), 2020, pp.15, e0232819~
- Li P, "Effects of high progesterone on outcomes of in vitro fertilization-embryo transfer in patients with different ovarian responses", Syst Biol Reprod Med, 61, pp.161~167 (2015)
- Li Q, "Decreased ovarian function and autophagy gene methylation in aging rats", J Ovarian Res, 13, pp.12~ (2020)
- Macklon NS, "The science behind 25 years of ovarian stimulation for in vitro fertilization", Endocr Rev, 27, pp.170~207 (2006)
- Nagata S, "Fas-induced apoptosis", Intern Med, 37, pp.179~181 (1998)
- Nie X, "Establishment of a mouse model of premature ovarian failure using consecutive superovulation", Cell Physiol Biochem, 51, pp.2341~2358 (2018)
- Santos MA, "The impact of ovarian stimulation for IVF on the developing embryo", Reproduction, 139, pp.23~34 (2010)
- Wang Z, "Prostaglandin F2α-induced functional regression of the corpus luteum and apoptosis in rodents", J Pharmacol Sci, 92, pp.19~27 (2003)
- Xi X, "Dynamic changes of DNA methylation and transcriptome expression in porcine ovaries during aging", BioMed Res Int, 2019, pp.8732023~ (2019)
- Yan P, "Long-term effects of repeated superovulation on the uterus and mammary gland in rhesus monkeys", J Assist Reprod Genet, 34, pp.535~545 (2017)
- Yu YS, "Apoptosis in granulosa cells during follicular atresia : Relationship with steroids and insulin-like growth factors", Cell Res, 14, pp.341~346 (2004)
- Zou Z, "mTOR signaling pathway and mTOR inhibitors in cancer : Progress and challenges", Cell Biosci, 10, pp.31~ (2020)