FIGURE 1.

Inflammatory mediators involved in the pathophysiology of PCOS.

Visceral adipocytes induce insulin activity, leading to impaired glucose tolerance, hyperinsulinemia, and insulin resistance. Hyperinsulinemia mimics the trophic action of LH in theca cells, increasing androgen production. Lastly, adipose tissue is rich in active immune cells (macrophages, monocytes) that secrete cytokines (IL-6, TNF-α, IL-1, MCP-1) associated with the inflammatory cascade in PCOS. The polarization of visceral adipose macrophages from M2 to M1 exacerbates the proinflammatory cytokine release from adipocytes. Peripheral immune cell abnormalities include a Th1 and Th17 bias, Treg cell reduction, and NK cell elevation. Notably, elevated IL-1β and IL-18 is seen in follicular fluid of patients with PCOS with evidence of NF-κB pathway activation and NLRP3 inflammasome formation in ovarian granulosa cells. The associated ovarian pathology includes altered steroidogenesis, hyperandrogenism, granulosa cell and luteal apoptosis, arrested follicular development, chromosomal maturation defects in oocytes, and poor oocyte quality. Impairment in uNK cell recruitment and disruption of essential cellular and cytokine pathways involved in implantation, altered oocyte quality, and anovulation are responsible for the resultant subfertility associated with PCOS.