Fetal hypoxia exposure induces Hif1a activation and autophagy in adult ovarian granulosa cells
文献类型：期刊论文
| 作者 | Zhang, Lu-Yao; Zhang, Ke; Zhao, Xi; Tao, Hai-Ping; Jia, Gong-Xue; Fang, You-Gui; Hou, Yun-Peng; Yang, Qi-En |
| 刊名 | BIOLOGY OF REPRODUCTION
 |
| 出版日期 | 2024 |
| 英文摘要 | Environmental hypoxia adversely impacts the reproduction of humans and animals. Previously, we showed that fetal hypoxia exposure led to granulosa cell (GC) autophagic cell death via the Foxo1/Pi3k/Akt pathway. However, the upstream regulatory mechanisms underlying GC dysfunction remain largely unexplored. Here, we tested the hypothesis that fetal hypoxia exposure altered gene expression programs in adult GCs and impaired ovarian function. We established a fetal hypoxia model in which pregnant mice were maintained in a high-plateau hypoxic environment from gestation day (E) 0-16.5 to study the impact of hypoxia exposure on the ovarian development and subsequent fertility of offspring. Compared with the unexposed control, fetal hypoxia impaired fertility by disordering ovarian function. Specifically, fetal hypoxia caused mitochondrial dysfunction, oxidant stress, and autophagy in GCs in the adult ovary. RNA sequencing analysis revealed that 437 genes were differentially expressed in the adult GCs of exposed animals. Western blotting results also revealed that fetal exposure induced high levels of hypoxia-inducible factor 1-alpha (Hif1a) expression in adult GCs. We then treated granulosa cells isolated from exposed mice with PX-478, a specific pharmacological inhibitor of Hif1a, and found that autophagy and apoptosis were effectively alleviated. Finally, by using a human ovarian granulosa-like tumor cell line (KGN) to simulate hypoxia in vitro, we showed that Hif1a regulated autophagic cell death in GCs through the Pi3k/Akt pathway. Together, these findings suggest that fetal hypoxia exposure induced persistent Hif1a expression, which impaired mitochondrial function and led to autophagic cell death in the GCs of the adult ovary. |
| 源URL | [http://210.75.249.4/handle/363003/61924]  |
| 专题 | 西北高原生物研究所_中国科学院西北高原生物研究所 |
| 推荐引用方式 GB/T 7714 | Zhang, Lu-Yao,Zhang, Ke,Zhao, Xi,et al. Fetal hypoxia exposure induces Hif1a activation and autophagy in adult ovarian granulosa cells[J]. BIOLOGY OF REPRODUCTION,2024. |
| APA | Zhang, Lu-Yao.,Zhang, Ke.,Zhao, Xi.,Tao, Hai-Ping.,Jia, Gong-Xue.,...&Yang, Qi-En.(2024).Fetal hypoxia exposure induces Hif1a activation and autophagy in adult ovarian granulosa cells.BIOLOGY OF REPRODUCTION. |
| MLA | Zhang, Lu-Yao,et al."Fetal hypoxia exposure induces Hif1a activation and autophagy in adult ovarian granulosa cells".BIOLOGY OF REPRODUCTION (2024). |
入库方式： OAI收割
来源：西北高原生物研究所
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