Hum. Reprod. Advance Access originally published online on January 11, 2007
Human Reproduction 2007 22(4):961-967; doi:10.1093/humrep/del487
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Follicle growth is inhibited by benzo-[a]-pyrene, at concentrations representative of human exposure, in an isolated rat follicle culture assay
1 Centre for Reproductive Care, Hamilton Health Sciences, Hamilton, Ontario, Canada 2 Reproductive Biology Division, Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada 3 Health Canada, Ottawa, Ontario, Canada
3 To whom correspondence should be addressed at: Centre for Reproductive Care, West End Clinic, Hamilton Health Sciences, 690 Main Street West, Hamilton, Ontario, Canada L8S 1A4. Tel: +905 521 2100 ext. 76515; Fax: +905 521 2609; E-mail: nealm{at}hhsc.ca
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.
Key words: benzo-[a]-pyrene/cigarette smoke/fertility/folliculogenesis
Submitted on March 14, 2006; resubmitted on September 30, 2006; accepted on November 10, 2006.