Obstetrics and Gynecology Hospital of Fudan University.
Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases.
Biosci Trends. 2017 Sep 12;11(4):427-438. doi: 10.5582/bst.2017.01108. Epub 2017 Jul 17.
Female fertility declines with age as the number of ovarian follicles decreases and aneuploidy increases. Degradation of the cohesin complex might be responsible for age-related aneuploidy. Dehydroepiandrosterone (DHEA) can improve the ovarian reserve and reduce the rate of aneuploidy, but the relationship between DHEA and cohesin levels in oocytes is still unknown. The aim of the current study was to evaluate the effect of the supplement DHEA on ovarian function, including the number of follicles and cohesin levels in oocytes. C57BL/6J mice at 3 weeks, 6 weeks, 12 weeks, 6 months, and 10 months of age were used to obtain a systematic view into follicle apoptosis and cohesin levels in oocytes. Nine-month-old C57BL/6J mice were administered saline (n = 5), 17β-estradiol (100 µg/kg per day, n = 5), or DHEA (5mg/Kg per day, n = 5). After 4 weeks, aged mice were weighed and sacrificed, and ovarian tissue samples were prepared. Anti-VASA staining and HE staining were used to count the number of follicles. Anti-γHAX staining and TUNEL were used to measure follicle apoptosis and immunofluorescent staining was used to detect the levels of three oocyte cohesin subunits: REC8, SMC1β, and SMC3. Administration of the supplements 17β-estradiol and DHEA to aged mice increased the number of primordial and primary follicles and decreased the age-related apoptosis of follicles. Levels of the cohesin subunits REC8 and SMC1β declined with age, but DHEA and 17β-estradiol tended to delay that decline. The supplement DHEA increased the number of primordial and primary follicles in aged mice by inhibiting follicle apoptosis and tended to delay the decrease in cohesin levels in oocytes.
随着卵巢卵泡数量减少和非整倍体增加，女性生育能力会随着年龄的增长而下降。黏合蛋白复合物的降解可能是导致与年龄相关的非整倍体的原因。脱氢表雄酮（DHEA）可以改善卵巢储备并降低非整倍体的发生率，但 DHEA 与卵母细胞中黏合蛋白水平之间的关系尚不清楚。本研究旨在评估补充 DHEA 对卵巢功能的影响，包括卵泡数量和卵母细胞中黏合蛋白水平。使用 3 周、6 周、12 周、6 个月和 10 个月大的 C57BL/6J 小鼠获得对卵泡凋亡和卵母细胞中黏合蛋白水平的系统观察。给 9 个月大的 C57BL/6J 小鼠注射生理盐水（n = 5）、17β-雌二醇（100 µg/kg/天，n = 5）或 DHEA（5mg/Kg/天，n = 5）。4 周后，称重并处死老年小鼠，准备卵巢组织样本。使用抗-VASA 染色和 HE 染色计数卵泡数量。使用抗-γHAX 染色和 TUNEL 测量卵泡凋亡，并用免疫荧光染色检测三种卵母细胞黏合蛋白亚基：REC8、SMC1β 和 SMC3 的水平。给老年小鼠补充 17β-雌二醇和 DHEA 可增加原始卵泡和初级卵泡的数量，并减少与年龄相关的卵泡凋亡。随着年龄的增长，黏合蛋白亚基 REC8 和 SMC1β 的水平下降，但 DHEA 和 17β-雌二醇有延缓下降的趋势。DHEA 通过抑制卵泡凋亡增加老年小鼠原始卵泡和初级卵泡的数量，并倾向于延缓卵母细胞中黏合蛋白水平的下降。
