Disturbed Follicular Microenvironment in Polycystic Ovary Syndrome: Relationship to Oocyte Quality and Infertility

Abstract

Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with infertility and poor reproductive outcomes. The follicular fluid (FF) microenvironment plays a crucial role in oocyte development. This review summarizes evidence elucidating the alterations in FF composition in PCOS. Various studies demonstrated a pronounced proinflammatory milieu in PCOS FF, characterized by increased levels of cytokines, including but not limited to interleukin-6 (IL-6), tumor necrosis factor α, C-reactive protein, and IL-1β, concomitant with a reduction in anti-inflammatory IL-10. T lymphocytes and antigen-presenting cells are dysregulated in PCOS FF. PCOS FF exhibit heightened reactive oxygen species production and the accumulation of lipid peroxidation byproducts, and impaired antioxidant defenses. Multiple microRNAs are dysregulated in PCOS FF, disrupting signaling critical to granulosa cell function. Proteomic analysis reveals changes in pathways related to immune responses, metabolic perturbations, angiogenesis, and hormone regulation. Metabolomics identify disturbances in glucose metabolism, amino acids, lipid profiles, and steroid levels with PCOS FF. Collectively, these pathological alterations may adversely affect oocyte quality, embryo development, and fertility outcomes. Further research on larger cohorts is needed to validate these findings and to forge the development of prognostic biomarkers of oocyte developmental competence within FF. Characterizing the follicular environment in PCOS is key to elucidating the mechanisms underlying subfertility in this challenging disorder.

Keywords: follicular fluid; immune dysregulation; metabolites; miRNA; oxidative stress; polycystic ovary syndrome; proteomic analysis.