Cigarette smoke condensate induces aryl hydrocarbon receptor-dependent changes in gene expression in spermatocytes.
Cigarette smoke contains numerous compounds that cause oxidative stress and alter gene expression in many tissues, and cigarette smoking is correlated with male infertility. To identify mechanisms by which this occurs, we evaluated expression of antioxidant genes in mouse spermatocytes in response to cigarette smoke condensate (CSC). CSC exposure led to oxidative stress and dose-dependent up-regulation of Hsp90aa1, Ahr, Arnt, Sod1, Sod2, and Cyp1a1 expression in a mouse spermatocyte cell line. An antagonist of the aryl hydrocarbon receptor (AHR) abrogated several CSC-mediated changes in mRNA and protein levels. Consistent with these results, spermatocytes isolated by laser-capture microdissection from CSC-treated mice showed increased expression of several antioxidant genes. In vivo exposure to CSC was genotoxic to spermatocytes, resulting in apoptosis and disruptions to the seminiferous tubules. Our in vivo and in vitro data indicate that CSC-mediated damage to murine spermatocytes is AHR-dependent and is mediated by oxidative stress.
Department of Veterans Affairs Medical Center, St. Louis, MO, United States.
Prabagaran
P
Esakky
Deborah A
DA
Hansen
Andrea M
AM
Drury
Kelle H
KH
Moley
D000818:Animals; D017209:Apoptosis; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics; D002460:Cell Line; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D005786:Gene Expression Regulation / Q000502:physiology; D005979:Glutathione Peroxidase / Q000235:genetics; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics; D007473:Ion Channels / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D024101:Mitochondrial Proteins / Q000235:genetics; D018384:Oxidative Stress / Q000502:physiology; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D017382:Reactive Oxygen Species / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics* / Q000378:metabolism; D012906:Smoke; D013090:Spermatocytes / Q000473:pathology / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics; D013737:Testis / Q000502:physiology; D062789:Tobacco Products; D000071246:Uncoupling Protein 2
C497397:Arnt protein, mouse; D018841:HSP90 Heat-Shock Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D018336:Receptors, Aryl Hydrocarbon; D012906:Smoke; D000071246:Uncoupling Protein 2; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase; D019363:Cytochrome P-450 CYP1A1; D013482:Superoxide Dismutase