Mitochondrial Dysfunction in PCOS: Insights into Reproductive Organ Pathophysiology

Abstract

Polycystic ovary syndrome (PCOS) is a complex, but relatively common endocrine disorder associated with chronic anovulation, hyperandrogenism, and micro-polycystic ovaries. In addition to reduced fertility, people with PCOS have a higher risk of obesity, insulin resistance, and metabolic disease, all comorbidities that are associated with mitochondrial dysfunction. This review summarizes human and animal data that report mitochondrial dysfunction and metabolic dysregulation in PCOS to better understand how mitochondria impact reproductive organ pathophysiology. This in-depth review considers all the elements regulating mitochondrial quantity and quality, from mitochondrial biogenesis under the transcriptional regulation of both the nuclear and mitochondrial genome to the ultrastructural and functional complexes that regulate cellular metabolism and reactive oxygen species production, as well as the dynamics that regulate subcellular interactions that are key to mitochondrial quality control. When any of these mitochondrial functions are disrupted, the energetic equilibrium within the cell changes, cell processes can fail, and cell death can occur. If this process is ongoing, it affects tissue and organ function, causing disease. The objective of this review is to consolidate and classify a broad number of PCOS studies to understand how various mitochondrial processes impact reproductive organs, including the ovary (oocytes and granulosa cells), uterus, placenta, and circulation, causing reproductive pathophysiology. A secondary objective is to uncover the potential role of mitochondria in the transgenerational transmission of PCOS and metabolic disorders.

Keywords: PCOS; biogenesis; metabolism; mitochondria; mitochondrial dynamics; mtDNA; ovary; oxidative stress; placenta; polycystic ovary syndrome; uterus.

Figure 1

Key elements that regulate mitochondria number and function to influence cell processes and fate. Created with BioRender.com.

Figure 2

Summary of reported alterations in mitochondrial biogenesis, genome, ultrastructure, metabolism, dynamics, and ROS in the ovary, oocyte, granulosa cell, uterus, placenta, and peripheral blood and plasma of PCOS. Offspring exposure studies were excluded. Created with BioRender.com.