title: Paternal exposure to cigarette smoke condensate leads to reproductive sequelae and developmental abnormalities in the offspring of mice.
abstract: Paternal smoking is associated with infertility, birth defects and childhood cancers. Our earlier studies using cigarette smoke condensate (CSC) demonstrated several deleterious changes in male germ cells. Here, we hypothesize that chronic paternal exposure to CSC causes molecular and phenotypic changes in the sire and the offspring, respectively. In this mouse study, CSC caused DNA damage and cytotoxicity in testes via accumulation of benzo(a)pyrene (B[a]P) and cotinine. Decreased expression of growth arrest and DNA damage inducible alpha (Gadd45a), aryl hydrocarbon receptor (Ahr), and cyclin-dependent kinase inhibitor 1A (P21) was seen in CSC exposed testes. Apoptotic germ cell death was detected by induction of Fas, FasL, and activated caspase-3. The CSC-exposed males displayed reduction in sperm motility and fertilizing ability and sired pups with reduced body weight and crown-rump length, and smaller litter size with higher numbers of resorption. This model of CSC exposure demonstrates testicular toxicity and developmental defects in the offspring.
authors: Research, Department of Veterans Affairs Medical Center, St. Louis, MO, United States; Department of Obstetrics and Gynecology, Washington University School of Medicine in St. Louis, MO 63110, United States. Electronic address: esakkyp@wudosis.wustl.edu.
authors: Prabagaran
authors: P
authors: Esakky
authors: Research, Department of Veterans Affairs Medical Center, St. Louis, MO, United States.
authors: Deborah A
authors: DA
authors: Hansen
authors: Research, Department of Veterans Affairs Medical Center, St. Louis, MO, United States; Department of Obstetrics and Gynecology, Washington University School of Medicine in St. Louis, MO 63110, United States.
authors: Andrea M
authors: AM
authors: Drury
authors: Department of Obstetrics and Gynecology, Washington University School of Medicine in St. Louis, MO 63110, United States.
authors: Paul
authors: P
authors: Felder
authors: Department of Obstetrics and Gynecology, Washington University School of Medicine in St. Louis, MO 63110, United States.
authors: Andrew
authors: A
authors: Cusumano
authors: Department of Obstetrics and Gynecology, Washington University School of Medicine in St. Louis, MO 63110, United States. Electronic address: moleyk@wustl.edu.
authors: Kelle H
authors: KH
authors: Moley
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001564:Benzo(a)pyrene / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003367:Cotinine / Q000378:metabolism; D018568:Crown-Rump Length; D004249:DNA Damage; D005260:Female; D005327:Fetal Resorption / Q000139:chemically induced; D015870:Gene Expression / Q000187:drug effects; D008098:Litter Size / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D018812:Paternal Exposure / Q000009:adverse effects*; D012906:Smoke / Q000009:adverse effects*; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism; D062789:Tobacco Products
chemical_list: D012906:Smoke; D001564:Benzo(a)pyrene; D003367:Cotinine
keywords: Apoptosis; BCL2; Benzo(a)pyrene; CSC; Caudal sperm; Cotinine; Embryos; Fas; FasL; Fetuses; Spermatocytes