Reproduction. 2026 Feb 15:xaag025. doi: 10.1093/reprod/xaag025. Online ahead of print.
ABSTRACT
Evidence suggest that lipotoxicity can cause hyperandrogenesis, but little is known about the intra-ovarian environment of women with polycystic ovary syndrome (PCOS) and whether it displays features associated with lipotoxicity. The objective of this secondary analysis was to compare follicular fluid concentrations of testosterone, markers of lipid, lipid metabolism and inflammation between women with PCOS and without PCOS. We conducted a controlled cross-sectional study on 80 participants. Medical records were used to determine PCOS diagnosis: 15 women were identified as having PCOS, while 65 had a negative diagnosis. Inclusion criteria were 18 and 40 years old with a body mass index raging between 18 and 40 kg/m2. Follicular fluid was analysed for total testosterone, non-esterified fatty acids (NEFA), triglycerides, NEFA metabolites (acylcarnitines and C16/C13 ratio) and inflammatory cytokines. Compared to women without PCOS, women with PCOS had increased follicular fluid levels of testosterone (7.08 nM vs 0.29 nM), triglycerides (0.30 nM vs 0.17 nM), palmitoylcarnitine (43.7 nM vs 28.4 nM) IL-6 (13.04 pg/mL vs 8.9 pg/mL), while TNF-α remained similar. These differences remained statistically different after adjustment for BMI, except for IL-6. These group differences were also confirmed in paired analyses of 13 BMI-matched pairs of PCOS vs non-PCOS women, exception made for IL-6. In conclusion, intra-ovarian inflammation, but more importantly, lipid overexposure, may play a role in the pathogenesis of PCOS, probably through lipotoxic effects.
PMID:41691561 | DOI:10.1093/reprod/xaag025
