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.
Neal
Michael S
MS
Centre for Reproductive Care, Hamilton Health Sciences, Hamilton, Ontario, Canada. nealm@hhsc.ca
Zhu
Jiping
J
Holloway
Alison C
AC
Foster
Warren G
WG
D000328:Adult; D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002478:Cells, Cultured / Q000187:drug effects*; D005260:Female; D005298:Fertility / Q000187:drug effects*; D005307:Fertilization in Vitro; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006080:Ovarian Follicle / Q000187:drug effects* / Q000254:growth & development; D010053:Ovary / Q000187:drug effects; D051381:Rats; D012907:Smoking / Q000009:adverse effects*; D016896:Treatment Outcome
D001564:Benzo(a)pyrene