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Influence of hypothyroidism on oxidative stress,c-Fos expression,cell cycle,and apoptosis in rats testes
Authors:Jun-Ling Wang  Hao-Jun Zhang  Hui-Ling Wang  Ju-Wei Wang  Pan-Hong Gou  Zhong-Hui Ye
Institution:1. Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, Chinawangjl@lzu.edu.cn;3. Department of Hospital Infection, People's Hospital of Gansu Province, Lanzhou, China;4. Department of Integrated Chinese and Western Medicine Gynecology, Gansu Provincial Maternity and Child-care Hospital, Lanzhou, China;5. Department of Toxicology, School of Public Health, Lanzhou University, Lanzhou, China
Abstract:The molecular basis of male reproduction for cross-regulation between androgen and thyroid hormone axes is still rudimentary. This study aims to define a possible mechanism of hypothyroidism-induced reproductive influence with respect to sex hormone, mineral, sperm motility, oxidative stress, c-Fos expression, cell cycle, and apoptosis in rat testes. The Wistar rats were randomly divided into control group (NS) and hypothyroidism group 1 ml/100g BW/day, 0.1% propylthiouracil (PTU)] by intragastric gavage for 60 days. Blood samples were collected to measure the serum levels. The epididymis was excised to measure sperm motility and testes were excised to measure mineral, oxidative stress, c-Fos expression, cell cycle, and apoptosis. After 60 days, body weight, relative testes weight, triiodothyronine, and total thyroxine were all significantly decreased, whereas thyroid stimulating hormone was increased in the hypothyroidism group. A significant increase in sex hormone level of estradiol (E2) and significant decreases in testosterone (T) and T/E2 ratio were observed following PTU treatment. And sperm quality was also significantly changed. There were significant decreases in the contents of calcium (Ca2+) and zinc (Zn2+). On the other hand, malondialdehyde and hydrogen peroxide contents significantly increased, whereas the activity of superoxide dismutase, catalase and nitric oxide synthase and nitric oxide content significantly decreased in hypothyroid rats. The mRNA and protein expressions of c-Fos decreased significantly. The cell percentage in G0/G1 phase increased significantly, whereas decreased significantly in S and G2/M phases. Also, a significant increase in testicular cell apoptosis was observed in hypothyroid-treated rats. These results suggested that hypothyroidism could affect reproductive function in the form of changed sex hormone levels, sperm motility and testicular Ca2+ and Zn2+, and enhanced oxidative stress leading to c-Fos abnormal expression and increased apoptosis.
Keywords:hypothyroidism  male rat reproduction  oxidative stress  c-Fos  cell cycle and apoptosis
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