KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon 34054, Korea.
Int J Mol Sci. 2022 Aug 3;23(15):8614. doi: 10.3390/ijms23158614.
Repeated and prolonged stress causes hypothalamic-pituitary-adrenal (HPA) dysregulation. Excessive hypothalamic-pituitary-adrenal axis activity has been linked to inadequate activation of the hypothalamus-pituitary-ovarian axis, which controls the growth and development of ovarian follicles and oocytes. Therefore, we assessed the ovarian reserve under high-housing-density-induced prolonged stress, and investigated the mechanisms underlying diminished ovarian reserve in this study. Eight-week-old female C57BL/6 mice were housed for 10 weeks under different housing densities. We then assessed hormone levels, performed histology and immunohistochemistry analyses of ovarian follicles, evaluated ovarian mRNA expression, and measured angiotensin II-mediated apoptosis in vitro. More densely housed mice presented increased corticosterone levels and decreased follicle-stimulating and luteinizing hormone levels. Moreover, mice exposed to prolonged ordinary stress showed a reduced level of serum anti-Müllerian hormone and an increased number of atretic ovarian follicles. Stressed mice showed increased levels of angiotensinogen and angiotensin II in the ovaries and serum. Furthermore, our in vitro study confirmed that high-housing-density-related stress induced granulosa cell apoptosis, resulting in diminished ovarian reserves. Collectively, our findings highlight the importance of women managing everyday stress to maintain their reproductive health.
反复和长期的压力会导致下丘脑-垂体-肾上腺（HPA）失调。过多的下丘脑-垂体-肾上腺轴活动与控制卵巢卵泡和卵子生长发育的下丘脑-垂体-卵巢轴的激活不足有关。因此，我们在高住房密度诱导的长期应激下评估了卵巢储备功能，并在本研究中研究了导致卵巢储备减少的机制。将 8 周龄的雌性 C57BL/6 小鼠在不同的住房密度下饲养 10 周。然后我们评估了激素水平，对卵巢卵泡进行组织学和免疫组织化学分析，评估了卵巢 mRNA 表达，并测量了体外血管紧张素 II 介导的细胞凋亡。高密度住房的小鼠皮质酮水平升高，卵泡刺激素和黄体生成素水平降低。此外，暴露于长期普通应激的小鼠血清抗苗勒管激素水平降低，闭锁性卵巢卵泡数量增加。应激小鼠的卵巢和血清中的血管紧张素原和血管紧张素 II 水平升高。此外，我们的体外研究证实，与高密度住房相关的应激诱导了颗粒细胞凋亡，导致卵巢储备减少。总之，我们的研究结果强调了女性管理日常压力以维持生殖健康的重要性。
