Cigarette Smoke Condensate Inhibits Follicular Development, Oocyte Maturation, and Dysregulates Steroids Synthesis In Vitro: Implications for Human Fecundity.

Decreased fertility and poorer response to ovulation induction have been reported in women who smoke compared to non-smokers. The cytotoxic effects and underlying mechanisms of action of cigarette smoke on ovarian function are poorly defined. We therefore hypothesize that cigarette smoke condensate (CSC) will affect follicular development, steroidogenesis, cumulus cell differentiation and oocyte maturity. Isolated mouse follicles (100-130 µm) were cultured for 13 days (D13) in the absence (controls) or presence of increasing CSC concentrations (30-130 µg/ml). Follicular development and viability were recorded prior to refreshment on days 4 (D4), 8 (D8) and 12 (D12) of culture. On D12, follicle survival was determined and preovulatory follicles stimulated with r-hCG and EGF. Following 18h (D13) after stimulation, cumulus cell-oocyte complexes, oocyte diameter and nuclear maturation were determined. Steroid output in spent media was measured (ELISA) on D8 and D12 (E2), and D12 and D13 (P4). Follicular development was significantly (p<0.05) decreased at the preantral (D4; 130 µg/ml) and antral (D8 and D12) stages in CSC-treated groups. In addition, follicle survival was decreased in a dose dependent manner and significant in the highest treatment (90 and 130 µg/ml) groups. Oocyte diameter was similar between controls and CSC-exposed follicles, while oocyte maturation was significantly decreased in CSC-treated groups. E2 output decreased significantly at the preantral (D4; 90 and 130 µg/ml) stage, whereas P4 increased significantly prior to ovulation (D12), and decreased significantly on D13 in all treatment groups. We conclude that exposure to CSC disrupts follicular development, decreases follicle survival, disregulates steroidogenesis (E2 and P4), alters cumulus cell differentiation, and delays or blocks oocyte meiotic maturation. Thus, we suggest that cigarette smoking impairs human fecundity through direct adverse effects on folliculogenesis and oocyte maturation. (poster)