Toupance Simon, Fattet Anne-Julie, Thornton Simon N, Benetos Athanase, Guéant Jean-Louis, Koscinski Isabelle
DCAC, Université de Lorraine, Inserm, 54000 Nancy, France.
Laboratory of Biology of Reproduction, University Hospital of Nancy, 54000 Nancy, France.
Biomedicines. 2021 Jul 20;9(7):842. doi: 10.3390/biomedicines9070842.
Women's fertility is characterized both quantitatively and qualitatively mainly by the pool of ovarian follicles. Monthly, gonadotropins cause an intense multiplication of granulosa cells surrounding the oocyte. This step of follicular development requires a high proliferation ability for these cells. Telomere length plays a crucial role in the mitotic index of human cells. Hence, disrupting telomere homeostasis could directly affect women's fertility. Strongly expressed in ovaries, telomerase is the most effective factor to limit telomeric attrition and preserve ovarian reserve. Considering these facts, two situations of infertility could be correlated with the length of telomeres and ovarian telomerase activity: PolyCystic Ovary Syndrome (PCOS), which is associated with a high density of small antral follicles, and Premature Ovarian Failure (POF), which is associated with a premature decrease in ovarian reserve. Several authors have studied this topic, expecting to find long telomeres and strong telomerase activity in PCOS and short telomeres and low telomerase activity in POF patients. Although the results of these studies are contradictory, telomere length and the ovarian telomerase impact in women's fertility disorders appear obvious. In this context, our research perspectives aimed to explore the stimulation of ovarian telomerase to limit the decrease in the follicular pool while avoiding an increase in cancer risk.
女性的生育能力在数量和质量上主要由卵巢卵泡池来表征。每月,促性腺激素会使围绕卵母细胞的颗粒细胞大量增殖。卵泡发育的这一步骤要求这些细胞具有高增殖能力。端粒长度在人类细胞的有丝分裂指数中起着关键作用。因此,破坏端粒稳态可能直接影响女性的生育能力。端粒酶在卵巢中强烈表达,是限制端粒磨损和维持卵巢储备的最有效因素。考虑到这些事实,两种不孕情况可能与端粒长度和卵巢端粒酶活性相关:多囊卵巢综合征(PCOS),与小窦卵泡的高密度有关;卵巢早衰(POF),与卵巢储备过早下降有关。几位作者研究了这个课题,期望在PCOS患者中发现长端粒和强端粒酶活性,在POF患者中发现短端粒和低端粒酶活性。尽管这些研究结果相互矛盾,但端粒长度和卵巢端粒酶对女性生育障碍的影响似乎很明显。在此背景下,我们的研究方向旨在探索刺激卵巢端粒酶,以限制卵泡池的减少,同时避免癌症风险增加。