Sirtuins: Novel Players in Male Reproductive Health

The current lifestyle of "western societies" is based on excessive consumption of high-energy diets and physical inactivity. Such behavior has pressured biological systems towards the development of metabolic diseases. This increased incidence of metabolic disorders is also accompanied by a decline in male reproductive health, particularly among young males. Male fertility is sensitive to metabolic dysfunctions, such as diabetes mellitus, which disrupt the link between energy metabolism and reproduction. Evidences showed that compromised sperm parameters induced by diabetes are associated with impaired testicular metabolism, suggesting that deficient testicular bioenergetics contributes to a decline in spermatogenesis. Energy metabolism is a well-coordinated process that involves a network of carbohydrate, lipid and protein metabolic pathways. This intricate process is an act of balance between mitochondria and nucleus, governed by metabolic sensors, such as sirtuins. The emerging role of sirtuins in the control of metabolism has been highlighted, specially in cancer metabolism. Little attention has been given to their role in non-cancerous cells that exhibit a "Warburg-like metabolism", such as Sertoli cells. Spermatogenesis is highly dependent on glycolytic metabolism, since the lactate produced by Sertoli cells is the major substrate of germ cells. The regulation of sirtuins in the glycolytic metabolism not only increases their physiological relevance to the testicular environment, but also suggests that these proteins may control male fertility. This review will discuss the recent findings in the role of sirtuins in testicular metabolism and will address the concept that sirtuins can be a potential target to counteract subfertility/infertility promoted by diabetes mellitus.