title: The cigarette smoke constituent benzo[a]pyrene disrupts metabolic enzyme, and apoptosis pathway member gene expression in ovarian follicles.
abstract: Benzo[a]pyrene (B[a]P) is a prototypical polycyclic aromatic hydrocarbon (PAH) present in cigarette smoke. We previously showed that B[a]P adversely affects follicular development and survival. The objective of this study was to identify the key molecular pathways underlying B[a]P-induced abnormal follicular development. Isolated follicles (100-130 μm) from ovaries of F1 hybrid (C57BL/6j×CBA/Ca) mice were cultured for 8 (preantral/antral follicles) and 12 (preovulatory follicles) days in increasing concentrations of B[a]P (0 ng/mL [control] to 45 ng/mL). Expression of aryl hydrocarbon receptor (AhR), aryl hydroxylase steroidogenic enzyme, cell-cycle, and apoptotic genes were quantified. B[a]P exposure significantly (P<0.05) increased mRNA expression of Cyp1a1 in preantral/antral follicles and Cyp1b1, Bax and Hsp90ab1 in preovulatory follicles. No significant effect on mRNA expression of StAR, Cyp11a1, aromatase, Cdk4, Cdk2, Ccnd2, cIAP2, and survivin was observed. In conclusion, this study suggests that B[a]P exposure significantly affects the phase I enzymes and cell death genes during preantral/antral and preovulatory growth, and thus highlight the AhR signaling and apoptotis pathways in delayed follicle growth and decreased viability.
authors.affiliation: Department of Obstetrics & Gynecology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Jean Clair
authors.initials: JC
authors.lastname: Sadeu
authors.forename: Warren G
authors.initials: WG
authors.lastname: Foster
mesh_terms: D000818:Animals; D017209:Apoptosis; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001564:Benzo(a)pyrene / Q000633:toxicity*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics; D051379:Mice; D006080:Ovarian Follicle / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D012906:Smoke; D014026:Nicotiana; D051028:bcl-2-Associated X Protein / Q000235:genetics
chemical_list: C494827:Bax protein, mouse; D018841:HSP90 Heat-Shock Proteins; C107835:Hspca protein, mouse; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D012906:Smoke; D051028:bcl-2-Associated X Protein; D001564:Benzo(a)pyrene; D001189:Aryl Hydrocarbon Hydroxylases; C585498:Cyp1b1 protein, mouse; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1
keywords: Benzo[a]pyrene; Folliculogenesis; Ovary; PAHs; Polyhalogenated hydrocarbons; Toxicology