文献类型： 外文期刊

作者： Zhang, Luyao ¹ ; Liu, Kexiong ¹ ; Liu, Zhiqiang ¹ ; Tao, Haiping ³ ; Fu, Xiangwei ⁵ ; Hou, Jian ¹ ; Jia, Gongxue ² ; Hou, Yunpeng ¹ ;

作者机构： 1.China Agr Univ, Coll Biol Sci, State Key Lab Anim Biotech Breeding, Beijing, Peoples R China

2.Chinese Acad Sci, Northwest Inst Plateau Biol, Key Lab Adaptat & Evolut Plateau Biota, Xining, Qinghai, Peoples R China

3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China

4.Chinese Acad Sci, Northwest Inst Plateau Biol, Qinghai Prov Key Lab Anim Ecol Genom, Xining, Qinghai, Peoples R China

5.China Agr Univ, Coll Anim Sci & Technol, Natl Engn Lab Anim Breeding, Beijing Key Lab Anim Genet Improvement, Beijing, Peoples R China

6.Xinjiang Acad Agr & Reclamat Sci, State Key Lab Sheep Genet Improvement & Hlth Breed, Shihezi, Peoples R China

关键词： Autophagic cell death; Energy production impairment; Fetal-hypoxic expose; Mitochondrial dysfunction; PI3K/Akt/FoxO pathway; Melatonin

期刊名称：JOURNAL OF ADVANCED RESEARCH （ 影响因子：13.0； 五年影响因子：11.6 ）

ISSN： 2090-1232

年卷期： 2024 年 64 卷

页码：

收录情况： SCI

摘要： Introduction: Fetal hypoxia has long-term effects on postnatal reproductive functions and the mitochondrial impairments of ovarian granulosa cells may be one of the causes. Melatonin applied to mitigate mitochondrial dysfunction and autophagy in mammalian cells has been reported. However, the potential mechanisms by which fetal hypoxia damages reproductive function in neonatal female mice and the melatonin effects on this problem remain unclear. Objectives: This research aimed to explore the mechanism that fetal hypoxia damages reproductive function in neonatal female mice and attempt to improve the reproductive function by treating with melatonin in vivo and in vitro. . Methods: We established a fetal hypoxia model and confirmed that fetal hypoxia affects ovarian function by inducing GC excessive autophagy. Transcriptomic analysis, gene interference, cell immunofluorescence, immunohistochemistry and western blot were conducted to explore and verify the underlying mechanisms in mice GCs and KGN cells. Finally, melatonin treatment was executed on hypoxia-treated mice GCs and KGN cells and melatonin injection to fetal-hypoxia-treated mice to determine its effect. Results: The results of in vitro experiments found that fetal hypoxia led to mitochondrial dysfunction in ovarian GCs causing autophagic cell death. And the PI3K/Akt/FoxO pathway mediated the occurrence of this process by transcriptome analysis of ovarian GCs from normal and fetal hypoxia mice, which was further verified in mice GCs and KGN cells. Additionally, melatonin administration prevented autophagic injuries and mitochondrial impairments in hypoxia-treated mice GCs and KGN cells. Meanwhile, in vivo experiments by melatonin injection ameliorated oxidative stress of ovary in fetal-hypoxiatreated mice and improved their low fertility. Conclusion: Our data found that fetal hypoxia causes ovarian GCs excessive autophagy leading to low fertility in neonatal female mice and mitigated by melatonin. These results provide a potential therapy for hypoxic stress-related reproductive disorders. (c) 2024 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).