Scholarlink

<p>Gain-of-function mutations in the human follicle-stimulating hormone receptor (FSHR) cause spontaneous ovarian hyperstimulation syndrome (OHSS), a serious reproductive disorder. However, the molecular physiology and treatment options for OHSS remain elusive. Notably, estrildid finches naturally carry an FSHR variant (Thr449Ala) analogous to the pathogenic mutation in humans yet are resistant to OHSS. Here we show that this resistance stems from significantly reduced luteinizing hormone receptor expression in estrildid ovarian granulosa cells. Furthermore, treatment with the luteinizing hormone receptor antagonist alleviates OHSS symptoms in mouse models. Single-cell RNA transcriptomic reveals functional compensation of the two receptors to regulate estrogen production and vascular permeability, resembling the adaptive mechanisms observed in estrildid finches. Our study unravels the molecular mechanism underlying the physiological adaptation of estrildid ovaries to high FSHR constitutive activity and is a example of how the concept of Darwinian Medicine could be exploited to identify novel drug targets for ovarian hyperstimulation syndrome treatment.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

FSHR and LHR functional compensation reveals the mechanism and treatment of Ovarian Hyperstimulation Syndrome

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月1日

查看全文
  • Shanshan Lai,
  • Yongjie Huang,
  • Su Ma,
  • Hongying Hao,
  • Ao Dai,
  • Xiaofei Yan,
  • Jiabao Yang,
  • Shuqian Wang,
  • Qingqing Ren,
  • Yan Zhang,
  • Peng Hu,
  • Jing Li,
  • Xiaowei Zheng,
  • Juergen Brosius,
  • Cheng Deng

摘要

Gain-of-function mutations in the human follicle-stimulating hormone receptor (FSHR) cause spontaneous ovarian hyperstimulation syndrome (OHSS), a serious reproductive disorder. However, the molecular physiology and treatment options for OHSS remain elusive. Notably, estrildid finches naturally carry an FSHR variant (Thr449Ala) analogous to the pathogenic mutation in humans yet are resistant to OHSS. Here we show that this resistance stems from significantly reduced luteinizing hormone receptor expression in estrildid ovarian granulosa cells. Furthermore, treatment with the luteinizing hormone receptor antagonist alleviates OHSS symptoms in mouse models. Single-cell RNA transcriptomic reveals functional compensation of the two receptors to regulate estrogen production and vascular permeability, resembling the adaptive mechanisms observed in estrildid finches. Our study unravels the molecular mechanism underlying the physiological adaptation of estrildid ovaries to high FSHR constitutive activity and is a example of how the concept of Darwinian Medicine could be exploited to identify novel drug targets for ovarian hyperstimulation syndrome treatment.