Mu Lu, Wang Ge, Yang Xuebing, Liang Jing, Tong Huan, Li Lingyu, Geng Kaiying, Bo Yingnan, Hu Xindi, Yang Ruobing, Xu Xueqiang, Zhang Yan, Zhang Hua
State Key Laboratory of Animal Biotech Breeding, College of Biological Sciences, China Agricultural University, Beijing, China.
Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China.
Nat Commun. 2025 Jan 2;16(1):72. doi: 10.1038/s41467-024-55509-y.
Ovarian function declines significantly as females enter middle-age, but the mechanisms underlying this decline remain unclear. Here, we utilize whole-organ imaging to observe a notable decrease in ovarian blood vessel (oBV) density and angiogenesis intensity of middle-aged mice. This leads to a diminished blood supply to the ovaries, resulting in inadequate development and maturation of ovarian follicles. Utilizing genetic-modified mouse models, we demonstrate that granulosa cell secreted VEGFA governs ovarian angiogenesis, but the physiological decline in oBV is not attributed to VEGFA insufficiency. Instead, through single-cell sequencing, we identify the aging of the ovarian vascular endothelium as the primary factor contributing to oBV decline. Consequently, the administration of salidroside, a natural compound that is functional to reverse oBV aging and promote ovarian angiogenesis, significantly enhances ovarian blood supply and improve fertility in older females. Our findings highlight that enhancing oBV function is a promising strategy to boost fertility in females.
随着女性步入中年，卵巢功能显著衰退，但其衰退的潜在机制仍不清楚。在此，我们利用全器官成像观察到中年小鼠的卵巢血管（oBV）密度和血管生成强度显著降低。这导致卵巢血液供应减少，进而造成卵巢卵泡发育和成熟不足。利用基因编辑小鼠模型，我们证明颗粒细胞分泌的VEGFA调控卵巢血管生成，但oBV的生理性下降并非归因于VEGFA不足。相反，通过单细胞测序，我们确定卵巢血管内皮细胞衰老为导致oBV下降的主要因素。因此，红景天苷（一种具有逆转oBV衰老和促进卵巢血管生成功能的天然化合物）的给药显著增加了老年雌性小鼠的卵巢血液供应并提高了其生育能力。我们的研究结果表明，增强oBV功能是提高雌性生育能力的一个有前景的策略。
