卵巢PERK/NRF2/CX43/StAR/孕激素通路的激活介导冷暴露引起的女性生殖功能障碍
Mengnan Ding1, Yarong Lu1,2, Qing Wen1
1Beijing Institute of Basic Medical Sciences, Beijing, 100850, China.
Scientific reports
|May 3, 2024
概括
暴露于寒冷会通过激活卵巢细胞中的PERK/NRF2/CX43/StAR/孕激素通路来破坏女性生殖系统. 准PERK可能会保护生殖健康免受寒冷压力.
科学领域:
- 生殖生物学 生殖生物学
- 环境健康 环境健康
- 细胞应激反应的应激反应
背景情况:
- 环境温度显著影响人类健康,低温对女性生殖功能构成风险.
- 由于感冒引起的女性生殖障碍的确切机制尚不清楚.
研究的目的:
- 研究冷气暴露影响女性生殖系统的分子机制.
- 确定潜在的治疗点,以减轻感冒引起的生殖功能障碍.
主要方法:
- 雌性小鼠被暴露在寒冷的条件下 (4°C).
- 初级颗粒细胞 (GCs) 在寒冷条件下培养或用异二醇处理.
- 其中的技术包括西斑,RT-PCR,co-IP,ELISA,药理抑制和siRNA敲击.
- 这项研究研究了荷尔蒙,间隙结蛋白和ER应激通路.
主要成果:
- 寒冷暴露导致小鼠的雌性循环障碍和卵泡发育不良.
- 孕激素及其合成酶StAR在卵巢GC中被上调.
- 连素43 (CX43) 表达增加,导致孕激素升高.
- ER压力传感器PERK的激活导致了NRF2-依赖的CX43转录和增加的孕激素合成.
- 抑制PERK可以扭转感冒引起的生殖问题.
结论:
- 暴露于寒冷会触发卵巢GC中涉及PERK,NRF2,CX43,Star和孕激素的途径,导致生殖功能障碍.
- 准PERK显示了在寒冷条件下保护女性生殖健康的前景.
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