The impact of follicle-stimulating hormone receptor mutations on female ovarian function and pregnancy outcomes: a systematic review

作者：Zhan Qing Qu, Bei Yang, Yaping Miao, Bei Wang, Shi Han, Chenchen Cui, Cuilian Zhang, Hua Zhao · 发表于：Biology of Reproduction · 年份：2025 · DOI：10.1093/biolre/ioaf283 · 被引用次数：2 · 研究领域：Ovarian function and disorders、Reproductive Biology and Fertility、Hypothalamic control of reproductive hormones

As a member of the G protein-coupled receptor (GPCR) family, the follicle-stimulating hormone receptor (FSHR) plays a central role in the regulation of female reproduction. By specifically binding to follicle-stimulating hormone (FSH), FSHR regulates the proliferation and differentiation of granulosa cells, follicular development and estradiol (E2) synthesis. In this article, we summarized 37 clinically relevant mutations of the FSHR gene. These mutations are classified according to their functional impacts as follows: (1) Inactivating mutations are primarily located in the extracellular domain (ECD; e.g., p.Ala189Val) and the transmembrane domain (TMD; e.g., p.Asp224Val). These mutations cause receptor expression defects or signaling impairment, clinically manifesting as resistant ovary syndrome (ROS), premature ovarian failure (POF), or related disorders. These conditions are typically characterized by a preserved primordial follicle reserve but an arrested antral follicle development; (2) Activating mutations are concentrated in the TMD (e.g., p.Asp567Gly) and intracellular loops (ICLs; e.g., p.Val514Ala). They exhibit relaxed ligand specificity and result in ligand-independent constitutive activation. This leads to pregnancy-associated spontaneous ovarian hyperstimulation syndrome (sOHSS), characterized by enlarged ovaries containing multiple follicles and supraphysiologically elevated E2 levels. The review highlights the clinical utility of in vitro maturation (IVM) tech...