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HIF-1α对卵泡发育及排卵生物学作用的研究进展

马林纳¹, 马堃², 范晓迪^3,*, 张涵¹, 李佳妮⁴, 高山凤⁴

¹天津中医药大学研究生院，天津 301617；²中国中医科学院继续教育处，北京 100700；³中国中医科学院西苑医院基础医学研究所中药药理北京市重点实验室，北京 100091；⁴中国中医科学院西苑医院妇科，北京 100091

摘要

低氧诱导因子-1α (hypoxia inducible factor-1α, HIF-1α)作为缺氧感应因子，通过调控卵泡的发育和排出影响女性的生殖功能。HIF-1α促进卵母细胞发育，调控其分泌相关血管生成因子，诱导颗粒细胞进行糖酵解、自噬，提高卵泡成熟率。此外，HIF-1α推动卵泡囊黄体化进程，维持黄体功能，最终通过累积氧化应激完成生理性黄体萎缩。若HIF-1α调控功能异常，则会引起血管新生障碍、能量代谢失常、过度氧化应激和异常自噬-凋亡等一系列病理反应，导致排卵障碍性不孕的发生。本文通过对近期关于HIF-1α调控卵泡发育、排出，以及黄体功能维持和结构萎缩的研究进行总结，阐述相关药物或有效成分通过HIF-1α对卵泡发育不良和卵子排出障碍的有效干预机制，以期为解决排卵障碍性不孕提供更系统、深入的研究思路。

关键词： 低氧诱导因子-1α; 卵泡发育; 排卵过程

Research progress on the biological effects of HIF-1α on follicle development and ovulation

MA Lin-Na¹, MA Kun², FAN Xiao-Di^3,*, ZHANG Han¹, LI Jia-Ni⁴, GAO Shan-Feng⁴

¹Graduate School, Tianjin University of Chinese Medicine, Tianjin 301617, China；²Department of Continuing Education, China Academy of Chinese Medical Sciences, Beijing 100700, China；³Beijing Key Laboratory of Traditional Chinese Medicine Pharmacology, Institute of Basic Medical Sciences, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China；⁴Gynecology Department, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China

Abstract

Hypoxia inducible factor-1α (HIF-1α), as a hypoxia inducible factor, affects women’s reproductive function by regulating the development and excretion of follicles. HIF-1α induces glycolysis and autophagy in the granule cells by promoting oocyte development, regulating the secretion of related angiogenic factors, and improving follicle maturity. In addition, HIF-1α promotes the process of luteinization of follicular vesicles, maintains luteal function, and finally completes physiological luteal atrophy through cumulative oxidative stress. Dysfunction of HIF-1α will cause a series of pathological consequences, such as angiogenesis defect, energy metabolism abnormality, excessive oxidative stress and dysregulated autophagy and apoptosis, resulting in ovulation problem and infertility. This article summarizes the previous studies on the regulation of follicle development and excretion and maintenance of luteal function and structural atrophy by HIF-1α. We also describe the effective intervention mechanism of related drugs or bioactive ingredients on follicular dysplasia and ovulation disorders through HIF-1α, in order to provide a systematic and in-depth insights for solving ovulation disorder infertility.

Key words: hypoxia inducible factor-1α; follicular development; ovulation

收稿日期：　　录用日期：

通讯作者：范晓迪　　E-mail: xiaodi.1018@163.com

DOI: 10.13294/j.aps.2023.0068

引用本文：

马林纳, 马堃, 范晓迪, 张涵, 李佳妮, 高山凤. HIF-1α对卵泡发育及排卵生物学作用的研究进展[J]. 生理学报 2023; 75 (5): 727-735.

MA Lin-Na, MA Kun, FAN Xiao-Di, ZHANG Han, LI Jia-Ni, GAO Shan-Feng. Research progress on the biological effects of HIF-1α on follicle development and ovulation. Acta Physiol Sin 2023; 75 (5): 727-735 (in Chinese with English abstract).