Ge Lei, Yang Yali, Xiao Tianxia, Gao Yuqing, Chang Wakam, Du Feifei, Yu Ming, Zhang Jian V
Center for Energy Metabolism and Reproduction, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Int J Mol Sci. 2025 Apr 2;26(7):3313. doi: 10.3390/ijms26073313.
Ovarian endometriosis (OEM) is a chronic inflammatory condition that impairs ovarian function. While its effects on ovarian reserve are well established, the long-term consequences of OEM on ovarian dysfunction, premature ovarian failure (POF), and systemic health, particularly in the context of accelerated aging, remain insufficiently studied. In this study, we employed an OEM mouse model and bulk RNA sequencing to investigate the underlying mechanisms. Our results show that OEM accelerates primordial follicle depletion and upregulates mTOR signaling pathway gene expression, along with mechanical stress and paracrine signaling via the Hippo and Myc pathways. OEM also induces irregular estrus and ovarian fibrosis in aging mice, decreases serum AMH levels, and increases FSH levels. Systemically, elevated serum IgG levels contribute to osteoporosis and cognitive decline, both linked to ovarian dysfunction and POF in OEM. These findings elucidate the mechanisms driving premature ovarian reserve depletion in OEM and highlight its broader systemic effects. This study emphasizes the importance of monitoring ovarian health and ectopic tissue to safeguard ovarian reserves and mitigate long-term risks such as osteoporosis and cognitive decline.
卵巢子宫内膜异位症（OEM）是一种损害卵巢功能的慢性炎症性疾病。虽然其对卵巢储备的影响已得到充分证实，但OEM对卵巢功能障碍、卵巢早衰（POF）和全身健康的长期后果，尤其是在加速衰老的背景下，仍研究不足。在本研究中，我们采用OEM小鼠模型和批量RNA测序来研究其潜在机制。我们的结果表明，OEM加速原始卵泡耗竭，上调mTOR信号通路基因表达，同时通过Hippo和Myc通路产生机械应激和旁分泌信号。OEM还可诱导衰老小鼠出现不规则发情和卵巢纤维化，降低血清AMH水平，并升高FSH水平。在全身水平上，血清IgG水平升高会导致骨质疏松和认知能力下降，这两者均与OEM中的卵巢功能障碍和POF有关。这些发现阐明了OEM中卵巢储备过早耗竭的机制，并突出了其更广泛的全身影响。本研究强调了监测卵巢健康和异位组织以保护卵巢储备并减轻骨质疏松和认知能力下降等长期风险的重要性。
