Follicle growth is inhibited by benzo-[a]-pyrene, at concentrations representative of human exposure, in an isolated rat follicle culture assay

BACKGROUND: The adverse effects of cigarette smoking on human fertility have been well documented. However, the mechanism(s) underlying the detrimental effects of cigarette smoking are unknown. Using a novel isolated rat follicle culture assay, we tested the hypothesis that benzo-[a]-pyrene (B[a]P), a constituent of cigarette smoke, can inhibit follicle growth. METHODS: B[a]P levels were quantified in the serum and follicular fluid (FF) of women undergoing in vitro fertilization (IVF) treatment exposed to mainstream smoke (n = 19) and non-smokers (n = 10) by gas chromatography mass spectrometry. Isolated rat follicles were cultured with increasing concentrations of B[a]P (1.5-300 ng ml(-1)) and follicle diameter was measured daily. RESULTS: Mean ( +/- Standard error of the mean) B[a]P) was quantified in the serum (0.40 +/- 0.13 ng ml(-1)) and FF (1.32 +/- 0.68 ng ml(-1)) of women who smoke. IVF stimulation and outcome measures were similar between female smokers and non-smokers with the exception of implantation rate and pregnancy rate, which were both significantly lower (P < 0.05) in the MS group. B[a]P treatment significantly reduced rat follicle diameter and attenuated FSH stimulated growth in a dose-dependent manner, beginning at 1.5 ng ml(-1). CONCLUSIONS: Our data suggest that B[a]P, at levels representative of those measured in human FF, may adversely affect follicle development and be an ovarian toxicant.