Paternal exposure to cigarette smoke condensate leads to reproductive sequelae and developmental abnormalities in the offspring of mice |
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| Institution: | 1. Research, Department of Veterans Affairs Medical Center, St. Louis, MO, United States;2. Department of Obstetrics and Gynecology, Washington University School of Medicine in St. Louis, MO 63110, United States;1. Department of Animal Science and Reproductive and Developmental Sciences Program, Michigan State University, United States;2. California National Primate Research Center and Department of Obstetrics and Gynecology, University of California, Davis, CA 95616, United States;1. Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 3M2, Canada;2. Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario M5S 3M2, Canada;1. Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN, United States;2. Office of Science Coordination and Policy (OSCP), Office of Chemical Safety and Pollution Prevention, U.S. EPA, Washington, D.C., United States;1. Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071, China;2. Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China;3. UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy, France;4. Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China |
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| 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 (Ba]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. |
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| Keywords: | CSC Spermatocytes Apoptosis Caudal sperm Cotinine Benzo(a)pyrene Fas FasL BCL2 Embryos Fetuses |
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