Medical Molecular Biology Laboratory, Medical College, Jinhua Polytechnic, Jinhua, Zhejiang Province, China.
Center of Clinical Reproductive Medicine, Jinhua People's Hospital, Jinhua, Zhejiang Province, China.
Biomed Res Int. 2020 Jun 30;2020:1946853. doi: 10.1155/2020/1946853. eCollection 2020.
This study aimed to investigate whether chronic unpredictable mild stress (CUMS) affects follicular development in ovaries through the nerve growth factor (NGF)/high affinity nerve growth factor receptor, the Tropomyosin-related kinase A (TrkA) receptor, mediated signaling pathway and to reveal the relationship between chronic stress and premature ovarian insufficiency (POI) development. In this experiment, a CUMS rat model was constructed. It was found that serum estradiol (E2), anti-Mullerian hormone (AMH), and gonadotropin-releasing hormone (GnRH) levels decreased, while follicle-stimulating hormone (FSH) levels increased. The expression of NGF, TrkA, p75, and FSHR in ovarian tissue decreased significantly. The expression levels of TrkA and p75 protein in ovarian stroma and small follicles were observed by an immunofluorescence assay. In addition, the numbers of small follicles were significantly reduced. The expression of TrkA, p75, and FSHR in CUMS ovarian tissue was upregulated by exogenous NGF . Furthermore, after treatment with NGF combined with FSH, E2 secretion in ovarian tissue culture supernatant of CUMS rats also increased significantly. Therefore, CUMS downregulates NGF and TrkA and promotes the occurrence of POI in rats. Exogenous NGF and FSH can upregulate the NGF receptor, E2, and AMH , and improve the rat ovarian function. Future studies may associate these results with female population.
本研究旨在探讨慢性不可预测轻度应激（CUMS）是否通过神经生长因子（NGF）/高亲和力神经生长因子受体、原肌球蛋白相关激酶 A（TrkA）受体介导的信号通路影响卵巢卵泡发育，并揭示慢性应激与卵巢早衰（POI）发展之间的关系。在本实验中，构建了 CUMS 大鼠模型。结果发现，血清雌二醇（E2）、抗苗勒管激素（AMH）和促性腺激素释放激素（GnRH）水平降低，而卵泡刺激素（FSH）水平升高。卵巢组织中 NGF、TrkA、p75 和 FSHR 的表达明显下降。通过免疫荧光检测卵巢基质和小卵泡中 TrkA 和 p75 蛋白的表达水平。此外，小卵泡数量明显减少。外源性 NGF 可上调 CUMS 卵巢组织中 TrkA、p75 和 FSHR 的表达。此外，NGF 联合 FSH 处理后，CUMS 大鼠卵巢组织培养上清液中 E2 的分泌也明显增加。因此，CUMS 下调 NGF 和 TrkA，促进大鼠 POI 的发生。外源性 NGF 和 FSH 可上调 NGF 受体、E2 和 AMH，改善大鼠卵巢功能。未来的研究可能会将这些结果与女性人群联系起来。
