Effects of thyroid dysfunctions in the circadian rhythmicity of rat testis

Background: The circadian clock orchestrates the daily rhythmicity of physiological processes in all cells, including the gonadal axis components. Thyroid hormones (THs) regulate both sexes' reproduction homeostasis and steroidogenesis. Thyroid dysfunctions are associated with circadian disruption in a tissue and sex-dependent manner. This study aimed to investigate the effects of thyroid disorders on the rhythmicity of testis circadian clock and its outputs. Methods: Hypothyroidism and hyperthyroidism were induced in adult male rats and testicular gene expression was assessed every 3 h up to 24 h. Thyroid-stimulating hormone (TSH) and triiodothyronine (T3) serum levels were used to confirm the thyroid states in experimental groups. Rhythmic data were evaluated using One-way ANOVA and 24-h cosine curve data fitting within each group, followed by Two-way ANOVA and pairwise comparisons. Results: The expression of core clock components (Bmal1, Cry1, and Nr1d1), clock-controlled genes (Dbp, Dio3, and Star) and estrogen receptors (Esr1 and Esr2) exhibited circadian rhythmicity in control testis. Hypothyroidism disrupted the daily oscillations of Bmal1 and Esr2, reduced the mesor of Cry1, Dbp, and Dio3, altered the acrophase of Nr1d1, Cry1 and Esr1 expression, and induced a circadian oscillation on Star expression in testis. Hyperthyroidism disrupted the circadian rhythmicity of Cry1, Dio3 and Esr1 mRNA expression, phase-advanced Bmal1 expression and reduced the mesor of Bmal1 and Esr2 mRNA contents. Conclusion: Thyroid dysfunction impairs the rhythmicity of the testicular circadian clock and its outputs, as well as the daily expression of genes related to intracellular signaling of thyroid and sexual hormones, which may contribute to the pathogenesis of male reproductive disorders and the impairment of steroidogenesis and spermatogenesis observed under these thyroid dysfunctions.