Abstract：
OBJECTIVE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by menstrual irregularities, androgen excess, and polycystic ovarian morphology, but its pathogenesis remains largely unknown. This review focuses on how androgen excess influences the molecular basis of energy metabolism, mitochondrial function, and mitophagy in granulosa cells and oocytes, summarizes our current understanding of the pathogenesis of PCOS, and discuss perspectives on future research directions.
METHODS: A search of PubMed and Google Scholar databases were used to identify relevant studies for this narrative literature review.
RESULTS: Female offspring born of pregnant animals exposed to androgens recapitulates the PCOS phenotype. Abnormal mitochondrial morphology, altered expression of genes related to glycolysis, mitochondrial biogenesis, fission/fusion dynamics, and mitophagy have been identified in PCOS patients and androgenic animal models. Androgen excess causes uncoupling of the electron transport chain and depletion of the cellular adenosine 5\'-triphosphate pool, indicating further impairment of mitochondrial function. A shift toward mitochondrial fission restores mitochondrial quality control mechanisms. However, prolonged mitochondrial fission disrupts autophagy/mitophagy induction due to loss of compensatory reserve for mitochondrial biogenesis. Disruption of compensatory mechanisms that mediate the quality control switch from mitophagy to apoptosis may cause a disease phenotype. Furthermore, genetic predisposition, altered expression of genes related to glycolysis and oxidative phosphorylation, or a combination of these factors may also contribute to the development of PCOS.
CONCLUSIONS: In conclusion, fetuses exposed to a hyperandrogenemic intrauterine environment may cause the PCOS phenotype possibly through disruption of the compensatory regulation of the mitophagy-apoptosis axis.
METHODS: A search of PubMed and Google Scholar databases were used to identify relevant studies for this narrative literature review.
RESULTS: Female offspring born of pregnant animals exposed to androgens recapitulates the PCOS phenotype. Abnormal mitochondrial morphology, altered expression of genes related to glycolysis, mitochondrial biogenesis, fission/fusion dynamics, and mitophagy have been identified in PCOS patients and androgenic animal models. Androgen excess causes uncoupling of the electron transport chain and depletion of the cellular adenosine 5\'-triphosphate pool, indicating further impairment of mitochondrial function. A shift toward mitochondrial fission restores mitochondrial quality control mechanisms. However, prolonged mitochondrial fission disrupts autophagy/mitophagy induction due to loss of compensatory reserve for mitochondrial biogenesis. Disruption of compensatory mechanisms that mediate the quality control switch from mitophagy to apoptosis may cause a disease phenotype. Furthermore, genetic predisposition, altered expression of genes related to glycolysis and oxidative phosphorylation, or a combination of these factors may also contribute to the development of PCOS.
CONCLUSIONS: In conclusion, fetuses exposed to a hyperandrogenemic intrauterine environment may cause the PCOS phenotype possibly through disruption of the compensatory regulation of the mitophagy-apoptosis axis.
摘要：
目的：多囊卵巢综合征（PCOS）是一种常见的以月经不调为特征的内分泌紊乱，雄激素过量,多囊卵巢形态学，但其发病机制尚不清楚。本文综述了雄激素过量如何影响能量代谢的分子基础。线粒体功能，颗粒细胞和卵母细胞的线粒体自噬，总结了我们目前对PCOS发病机制的认识，并对未来的研究方向进行了展望。
方法：使用搜索PubMed和GoogleScholar数据库来确定本叙述性文献综述的相关研究。
结果：暴露于雄激素的怀孕动物所生的雌性后代概括了PCOS表型。线粒体形态异常,糖酵解相关基因的表达改变，线粒体生物发生，裂变/聚变动力学，并在PCOS患者和雄性激素动物模型中发现有丝分裂。雄激素过量导致电子传递链解偶联和细胞腺苷5'-三磷酸池耗尽，表明线粒体功能进一步受损。向线粒体裂变的转变恢复了线粒体质量控制机制。然而,由于线粒体生物发生的代偿储备丧失，延长的线粒体裂变会破坏自噬/线粒体自噬的诱导。介导质量控制从线粒体自噬转变为凋亡的代偿机制的破坏可能导致疾病表型。此外，遗传易感性,糖酵解和氧化磷酸化相关基因的表达改变，或这些因素的组合也可能有助于PCOS的发展。
结论：结论：暴露于高雄激素血症宫内环境的胎儿可能通过破坏线粒体自噬-凋亡轴的代偿调节而导致PCOS表型。
方法：使用搜索PubMed和GoogleScholar数据库来确定本叙述性文献综述的相关研究。
结果：暴露于雄激素的怀孕动物所生的雌性后代概括了PCOS表型。线粒体形态异常,糖酵解相关基因的表达改变，线粒体生物发生，裂变/聚变动力学，并在PCOS患者和雄性激素动物模型中发现有丝分裂。雄激素过量导致电子传递链解偶联和细胞腺苷5'-三磷酸池耗尽，表明线粒体功能进一步受损。向线粒体裂变的转变恢复了线粒体质量控制机制。然而,由于线粒体生物发生的代偿储备丧失，延长的线粒体裂变会破坏自噬/线粒体自噬的诱导。介导质量控制从线粒体自噬转变为凋亡的代偿机制的破坏可能导致疾病表型。此外，遗传易感性,糖酵解和氧化磷酸化相关基因的表达改变，或这些因素的组合也可能有助于PCOS的发展。
结论：结论：暴露于高雄激素血症宫内环境的胎儿可能通过破坏线粒体自噬-凋亡轴的代偿调节而导致PCOS表型。
