title: Follicle growth is inhibited by benzo-[a]-pyrene, at concentrations representative of human exposure, in an isolated rat follicle culture assay.
abstract: 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.
authors.affiliation: Centre for Reproductive Care, Hamilton Health Sciences, Hamilton, Ontario, Canada. nealm@hhsc.ca
authors.forename: Michael S
authors.initials: MS
authors.lastname: Neal
authors.forename: Jiping
authors.initials: J
authors.lastname: Zhu
authors.forename: Alison C
authors.initials: AC
authors.lastname: Holloway
authors.forename: Warren G
authors.initials: WG
authors.lastname: Foster
mesh_terms: 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
chemical_list: D001564:Benzo(a)pyrene