Androgen-Driven Dysregulation of Lipolysis in Cumulus Cells: Molecular Evidence and Metabolic Implications in Polycystic Ovary Syndrome.

OBJECTIVE: The present study aimed to investigate lipolytic function in cumulus cells (CCs) from women with polycystic ovary syndrome (PCOS), with a particular emphasis on the role of androgen excess. STUDY DESIGN: Samples of follicular fluid and CCs were collected from 30 PCOS and 30 control subjects. Human primary CCs were cultured and treated with high doses of testosterone. Androgen and gene expression levels were measured by chemiluminescent immunoassay and quantitative reverse transcription polymerase chain reaction, respectively. Oil Red O staining followed by spectrophotometric analysis was conducted to quantify intracellular neutral lipids. MAIN FINDINGS: CCs from PCOS patients showed significantly downregulated PNPLA2 and elevated G0S2 and HILPDA expression, with concomitant increased lipid droplet content (p < 0.05). The multivariable logistic regression model constructed from the combination of all three genes exhibited a superior diagnostic power (AUC = 0.837, p < 0.001). Only HILPDA expression was significantly correlated with intrafollicular testosterone (r = 0.395, p = 0.031), yet the main alterations observed in PCOS CCs were recapitulated in normal cells exposed to high doses of testosterone (p < 0.05). CONCLUSION: PCOS-associated hyperandrogenism appears to impair lipolysis in CCs, representing a potential mechanistic contributor to attendant compromised oocyte competence.