title: Quinestrol induces spermatogenic apoptosis in vivo via increasing pro-apoptotic proteins in adult male mice.
abstract: The effects of quinestrol on spermatogenesis were investigated in adult male mice by daily intragastric administration of quinestrol with various doses of 5, 10, 50 and 100mg/kg body weight for 10 days. The sperm counts declined while the number of abnormal spermatozoa went up in mice treated with quinestrol. The testicular weight and seminiferous tubular area gradually declined with increasing dosages of quinestrol to 50 and 100mg/kg. Rarefied germ cells showed irregular distributions in the seminiferous tubules of mice treated with 50 and 100mg/kg quinestrol. Apoptosis was highly pronounced in spermatogonia, spermatocytes, spermatids and Leydig cells. Antioxidant enzyme activities - superoxide dismutase and glutathione peroxidase - as well as total antioxidant capacity significantly reduced, while malondialdehyde contents increased. The number of germ cells expressing caspase-3, p53, Bax and FasL significantly increased whereas cells expressing Bcl-2 significantly decreased in groups treated with 50 and 100mg/kg quinestrol compared with the control. The concentration of nitrogen monoxidum also increased significantly under these dosages. The results suggest that quinestrol stimulates oxidative stress to induce apoptosis in spermatogenic cells through the mitochondrial and death receptor pathways in adult male mice.
authors.affiliation: Laboratory of Veterinary Anatomy, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China; Laboratory of Veterinary Anatomy, College of Animal Science and Technology, Henan University of Science and Technology, Luoyang 471000, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Yanjing Medical College, Capital Medical University, Beijing 101300, China.
authors.forename: Funing
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Environmental Toxicology, University of California, Davis, CA 95616, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Li
authors.affiliation: Laboratory of Veterinary Anatomy, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. Electronic address: yxchen@cau.edu.cn.
authors.forename: Yaoxing
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D011800:Quinestrol / Q000494:pharmacology*; D013094:Spermatozoa / Q000187:drug effects*
chemical_list: D051017:Apoptosis Regulatory Proteins; D004967:Estrogens; D011800:Quinestrol
keywords: Adult male mice; Apoptosis; Oxidative stress; Quinestrol; Spermatogenic cell