Effect of Light-Dark Cycle Misalignment on the Hypothalamic-Pituitary-Gonadal Axis, Testicular Oxidative Stress, and Expression of Clock Genes in Adult Male Rats

Abstract

This study investigated the influence of circadian misalignment on the male reproductive system. Adult Sprague-Dawley male rats were exposed to prolonged light (20 h light : 4 h dark) or prolonged darkness (4 h light : 20 h dark) for 12 consecutive weeks. The somatic index of seminal vesicles and prostates increased due to prolonged light exposure. Sperm count and motility were enhanced solely by prolonged light exposure, whereas the percentage of sperm abnormalities was reduced by both prolonged light and darkness. The serum levels of reproductive hormones (follicle-stimulating hormone, luteinizing hormone, testosterone, and prolactin) were elevated, and the estradiol level was reduced by long-term light and dark exposure. Testicular total antioxidant capacity and antioxidant enzyme activities were improved, and lipid peroxidation was inhibited following chronic exposure to light or dark. Chronic light exposure increased, but chronic darkness decreased, testicular nitric oxide production. The mRNA expression of the hypothalamic and testicular clock genes including PER1-2, CRY1-2, BMAL1, CLOCK, and Rev-Erbα was altered by circadian disruption. Prolonged light exposure decreased the levels of thyroid hormones and suppressed the mRNA expression of adiponectin receptors 1 and 2. The immunohistochemical expression of proliferating cell nuclear antigen was decreased only by chronic darkness. The present study thus provides new insights into the physiological changes associated with long-term exposure to light or darkness, in which the expression levels of various clock gene mRNAs are modulated, reproductive hormones are increased, and the antioxidant enzyme system is ameliorated as mechanisms of adaptation to chronic circadian disruption.