![]() ![]() Vitamin D3, also known as cholecalciferol, is generated by the activation of a cholesterol precursor in the skin, as the inactive form of vitamin D, due to ultraviolet B radiations. The aim of this review is to provide an updated systematic revision of the current available literature, analyzing the experimental and clinical evidence supporting the role for vitamin D in the regulation of testis hormone production, seminal parameters, and consequently male fertility. Nevertheless, a general consensus about the role of vitamin D in male fertility is still debated. Hypovitaminosis D has a negative impact on semen and hormone function, either in animals or in humans. To date, the key role of vitamin D in male reproductive system has been suggested, since the expression of VDR and vitamin D metabolizing enzymes was demonstrated in the testis and spermatozoa. Vitamin D plays its various biological effects through the binding and activation of vitamin D receptors (VDR). A specific 24-hydroxylase enzyme expressed in the kidney and in different target organs is responsible for the inactivation of all forms of vitamin D3. The inactive form of vitamin D3 partially derives from dietary sources, but it is mainly synthesized by the skin with a subsequent two step activation requiring first a hepatic enzyme, resulting in 25-hydroxy-vitamin D3 which is the substrate of a renal enzyme, producing 1-α,25-dihydroxy-vitamin D3, the final active form of vitamin D3. ![]() The two most biologically relevant members of the vitamin D group are ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3). Vitamin D deficiency (VDD) is an important risk factor not only for hyperparathyroidism, rickets, and osteomalacia, but also for further clinical conditions, such as obesity, thyroid dysfunction, autoimmune diseases, diabetes mellitus (DM), cardiovascular diseases, dementia, and cancer. However, recent studies have extended the spectrum of vitamin D target organs, including the adipose tissue, thyroid, immune system, pancreas, cardiovascular system, central nervous system, and the reproductive system as well. Thus, vitamin D plays multiple biological effects on each one of these organs. The principal target organs of vitamin D are intestine, skeletal system, kidneys, and parathyroid glands. ![]() The main activity of this molecule, belonging to secosteroids group, is the regulation of calcium and phosphorus homeostasis, promoting bone mineralization. In recent years, vitamin D has been considered an interesting subject of study due to its pleiotropic role, including autocrine, paracrine and endocrine function on several target organs and systems. Future studies are needed to better clarify the exact role of vitamin D on hormonal and seminal panel in both fertile and infertile men. However, all the previous studies displayed a wide heterogeneity in study design, population, methodology, and cut off values used for the evaluation of vitamin D status. Regarding pregnancy outcomes, normal level of vitamin D seems to be related to better pregnancies. As well as concerning the effect of vitamin D on semen parameters, most of the studies agreed in the possibility that vitamin D might have a positive effect on human male fertility potential, particularly through better sperm motility. Possible bias, including age, body mass index, and baseline vitamin D status justified the differences among studies. Equally, the experimental researches not were able to state a certain relationship between vitamin D status and testis hormone production. The consequences of vitamin D deficiency on serum levels of testicular hormones have been analysed by several observational and interventional studies, with controversial results. The aim of this review is to provide an updated systematic revision of the current available literature, discussing the experimental and clinical evidence on the role of vitamin D in the regulation of testis hormone production, seminal parameters and male fertility. To date, the key role of vitamin D in male reproductive system has been suggested, since the expression of vitamin D receptors and metabolizing enzymes was demonstrated in the testis and spermatozoa.
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