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在小鼠中,Bmal1通过下丘脑-垂体-卵巢轴调节雌性生殖

Ayuan Zhang^1,2, Shiping Li¹, Lingyi Huang³

¹Department of Pediatrics, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), NHC Key Laboratory of Chronobiology, West China Second University Hospital, Sichuan University, Chengdu, China.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

|June 17, 2024

概括

大脑和肌肉ARNT样蛋白1 (Bmal1) 缺乏,通过破坏下丘脑-垂体-淋巴腺轴,损害了小鼠的雌性生育能力. 恢复益生素或孕激素水平部分恢复生殖功能,突出Bmal1作为潜在的不孕目标.

科学领域:

神经内分泌学神经内分泌学
生殖生物学生殖生物学
时间生物学时间生物学

背景情况:

下垂体-垂体-腺 (HPG) 轴对于生殖调节至关重要.
大脑和肌肉ARNT样蛋白1 (Bmal1) 影响内分泌激素代谢.
在HPG轴和女性生育方面,Bmal1的特定作用在很大程度上仍未被描述.

研究的目的:

在小鼠模型中通过HPG轴研究Bmal1在雌性生殖中的调节作用.
阐明Bmal1影响卵巢功能和生育能力的机制.

主要方法:

使用CRISPR/Cas9技术生成Bmal1-淘汰赛 (Ko) 的小鼠.
在Bmal1-Ko和野生型 (Wt) 小鼠中评估卵巢结构,功能和雌性周期.
转录组分析,RT-PCR,免疫组织化学和西部涂抹来检查HPG轴基因/蛋白质表达.
在用益生素 (PRL) 和孕激素 (Pg) 干预后评估生育能力和生殖能力.

主要成果:

Bmal1-Ko小鼠表现出明显减少的后代数量,卵巢体重,卵泡数量和不规则的雌激周期.
在Bmal1-Ko卵巢中观察到黄体缺失和关键生殖基因的改变表达 (例如,减少Star,增加PRL和LH,减少DA和Pg).
在Bmal1-Ko小鼠中,通过抑制PRL或补充Pg来实现雌激素周期和卵巢功能的部分恢复.

结论:

缺乏Bmal1会通过增加PRL和降低多巴胺来破坏雌性生殖,从而损害白细胞形成,星表达和通过HPG轴的孕激素产生.
准PRL或孕激素通路为Bmal1相关的不孕症提供了潜在的治疗策略.
Bmal1成为女性生育能力的重要调节者,也是治疗不孕症治疗的潜在治疗点.

关键词:

Bmal1 的意思是什么?女人的生殖系统是女性的生殖系统.下垂体垂体阴茎轴

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