Mitochondrial Dynamics as Potential Modulators of Hormonal Therapy Effectiveness in Males

SIMPLE SUMMARY: Andrological diseases that affect patients in pediatric age represent important risk factors for alterations of their fertile potential in adulthood, and hence early diagnosis and treatment, even surgical and/or therapeutic treatments, are of primary importance. In this context, the discovery of the biological cues connected with alterations in the andrological sphere both in the pediatric age and adulthood could offer new insights into the identification of altered fertility potential markers or new therapeutic approaches. Mitochondria, the respiratory organelle of the cells, represent a key subcellular compartment within which the first enzymatic reaction of steroidogenesis takes place, thus highlighting that a correct arrangement of these organelles could be of crucial importance in both the correct hormone synthesis and response to hormonal therapies. ABSTRACT: Worldwide the incidence of andrological diseases is rising every year and, together with it, also the interest in them is increasing due to their strict association with disorders of the reproductive system, including impairment of male fertility, alterations of male hormones production, and/or sexual function. Prevention and early diagnosis of andrological dysfunctions have long been neglected, with the consequent increase in the incidence and prevalence of diseases otherwise easy to prevent and treat if diagnosed early. In this review, we report the latest evidence of the effect of andrological alterations on fertility potential in both young and adult patients, with a focus on the link between gonadotropins’ mechanism of action and mitochondria. Indeed, mitochondria are highly dynamic cellular organelles that undergo rapid morphological adaptations, conditioning a multitude of aspects, including their size, shape, number, transport, cellular distribution, and, consequently, their function. Since the first step of steroidogenesis takes place in these organelles, we consider that mitochondria dynamics might have a possible role in a plethora of signaling cascades, including testosterone production. In addition, we also hypothesize a central role of mitochondria fission boost on the decreased response to the commonly administrated hormonal therapy used to treat urological disease in pediatric and adolescent patients as well as infertile adults.