The impact of nandrolone decanoate (ND) on male reproductive health has been the subject of research. However, thymoquinone (TQ) may offer a potential modifier. This study aimed to explore the effects of TQ on rats subjected to ND. To this end, adult male Wistar rats were randomly divided into four groups over a 12-week period: the control group received no treatment, the ND group was administered ND at a dosage of 9 mg/kg/weeks, the ND + TQ group received both ND at 9 mg/kg/week and TQ at 50 mg/kg orally, and the TQ group received TQ at 50 mg/kg orally. Histomorphometric examination of the testes demonstrated damage resulting from ND, which was characterized by degenerated seminiferous tubules and affected lining cells. This was demonstrated by a decrease in seminiferous tubular diameter, epithelial height, and Johnsen scores. Nevertheless, TQ could improve this structural changes. Additionally, testes weight, sperm parameters, total antioxidant capacity, microRNA (miR)-202-5p expression, and the immuno-expressions of DDX4, SYCP3, and SOX9 were exhibited decreased in the ND group. Testosterone levels were lower in rats exposed to ND, accompanied by a rise in luteinizing hormone levels; however, TQ was able to alter this hormonal imbalance. Furthermore, ND exposure was related to increased levels of miR-122, malondialdehyde (MDA) and abnormal sperm morphology, while co-administration of TQ improved these changes. TQ rebalanced MDA and microRNA levels. Overall, TQ normalized ND-induced testicular damage probably through antioxidant and anti-inflammatory properties, miR altering, and enhancing germ cell activity.
