Quinestrol induces spermatogenic apoptosis in vivo via increasing pro-apoptotic proteins in adult male mice

• We examine changes in the antioxidative capacity and apoptosis-related proteins
• Reduced antioxidative capacity involved in infertility of mice
• Quinestrol induced testicular spermatogenic apoptosis

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 100 mg/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 100 mg/kg. Rarefied germ cells showed irregular distributions in the seminiferous tubules of mice treated with 50 and 100 mg/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 100 mg/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.