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Acute heat stress regulates estradiol synthesis in ovine ovarian granulosa cells through the SREBPs/MVK-LHR pathway

文献类型： 外文期刊

作者： Li, Yinxia 1 ; Li, Fan 1 ; Shu, Jiaao 1 ; Meng, Chunhua 1 ; Zhang, Jun 1 ; Zhang, Jianli 1 ; Qian, Yong 1 ; Wang, Huili 1 ; Ding, Qiang 1 ; Cao, Shaoxian 1 ;

作者机构： 1.Jiangsu Acad Agr Sci, Inst Anim Sci, Nanjing 210014, Peoples R China

2.Jiangsu Prov Engn Res Ctr Precis Anim Breeding, Nanjing 210014, Peoples R China

3.Minist Agr, Key Lab Crop & Anim Integrated Farming, Nanjing 210014, Peoples R China

关键词： Acute heat stress; Cholesterol; Estradiol; Mevalonate kinase; Sterol regulatory element-binding proteins; Luteinizing hormone receptor

期刊名称：ANIMAL REPRODUCTION SCIENCE （ 影响因子：3.3； 五年影响因子：2.6 ）

ISSN： 0378-4320

年卷期： 2025 年 272 卷

页码：

收录情况： SCI

摘要： The adverse effects of heat stress on reproductive performance of sheep are becoming increasingly severe. Previous research has revealed that heat stress decreases both cholesterol and estradiol content; however, regulation of estradiol by cholesterol and its regulatory mechanism under heat stress are unclear. Mevalonate kinase (MVK), a key cholesterol synthesis pathway enzyme, binds to the luteinizing hormone receptor (LHR; a key gene regulating hormone synthesis) mRNA. In this study, ovine ovarian granulosa cells (GCs) were used in an in vitro model. To elucidate the underlying molecular mechanism, immunofluorescence, quantitative reverse transcription polymerase chain reaction, western blotting, enzyme-linked immunosorbent assay, and an RNA electrophoretic mobility shift assay (REMSA) were used to investigate whether the decrease in cholesterol caused by acute heat stress resulted in a decrease in estradiol synthesis. Acute heat stress reduced the cholesterol content in ovine ovarian GCs, which transactivated the cholesterol synthesis pathway corresponding to the gene expression of sterol regulatory element-binding protein (SREBP-1A), SREBP-2, and MVK. Upregulated MVK increased the MVK-LHR mRNA complex, which caused LHR mRNA decay and downregulation, further leading to the downregulation of CYP19A1 and a decrease in estradiol. The cholesterol synthesis inhibitor, PF429242, alleviated the decrease in estradiol synthesis caused by acute heat stress. Overall, acute heat stress caused a decrease in total cholesterol, which transactivated the expression of cholesterol synthesis genes, such as SREBP-1A, SREBP2, and MVK, increasing the MVK-LHR complex, downregulating LHR expression, and further decreasing estradiol.

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