Metabolic Cooperation in Testis as a Pharmacological Target: From Disease to Contraception

Abstract

Abstract:The development of a "male pill" to control fertility is still a major challenge. Although women have several options to play an active role in the couple family planning, men are very limited in terms of contraceptive methods. Several approaches have been proposed to develop a male contraceptive and can be divided in two major groups: hormonal and non-hormonal methods. Within the testis, the somatic Sertoli cell (SC) is known as the "nurse cell" since it provides the physical and nutritional support for the developing germ cells. Moreover, adjacent SCs form the Sertoli/blood testis barrier (BTB), which divides the seminiferous epithelium into the basal and the apical compartments, controlling the passage of substances to the site where germ cells develop. Among the several functions of SC, its metabolism and the production of lactate, acetate and other metabolic factors are essential for the normal occurrence of spermatogenesis. In the last years, several works have highlighted that the metabolic cooperation established between SCs and developing germ cells is compromised in several diseases associated with male subfertility/infertility. Notably, several metabolismassociated proteins are specifically expressed in the testis. Thus, there are several evidences illustrating that the control of male fertility can be achieved by targeting testicular cells metabolism. Herein, we discuss the metabolic cooperation in testis as a potential pharmacological target to counteract subfertility/infertility promoted by several diseases, particularly metabolic diseases. We also discuss how it can contribute to the development of a male contraceptive.

Dehydroepiandrosterone and 7-oxo-dehydroepiandrosterone in male reproductive health: Implications of differential regulation of human Sertoli cells metabolic profile

“…Notably, low testosterone levels are often the basis of many fertility problems in men, mostly due to deficient spermatogenesis. Within the testis, hSCs transduce signals from testosterone, via androgen receptors, to produce essential factors for the spermatogenic process [44]. Thus, deficient or decreased testosterone production will compromise the unique metabolism of hSCs and hence germ cells successful development [35].…”

Immunohistochemical localization of glucose transporter 1 and 3 in the scrotal and abdominal testes of a dog

“…Uptake of glucose is controlled by specific glucose transporters (GLUTs) [3], which are reliant on its affinity to glucose in various organs. GLUT1, GLUT3, and GLUT8 are the main isoforms found in testes [4].…”

Mammalian target of rapamycin (mTOR): a central regulator of male fertility?

“…This was a first assessment on the effect of rapamycin in isolated human Sertoli cells, but the mechanisms by which mTOR may affect the nutritional support of spermatogenesis remain undisclosed, although it may also be a way by which mTOR controls spermatogenesis. Interestingly, alterations in Sertoli cells physiology and function have been suggested as pivotal for the development of subfertility or infertility associated with metabolic diseases (Alves et al , 2014, 2016a,b; Martins et al , 2015; Oliveira et al , 2015a). Indeed, mTOR has also been reported to be involved in the establishment of metabolic diseases (Laplante & Sabatini, 2012a,b) thus, it would be important to unveil the possible role of mTOR in subfertility or infertility induced by those pathological states.…”

“…In addition, current research highlights that mTOR is a crucial regulator of cellular homeostasis and metabolism, controlling several processes such as amino acid synthesis, glucose metabolism, cytoskeleton organization and many other functions. Metabolism is pivotal to spermatogenesis and thus, determines the fertility of males (for review see Alves et al, 2014; Rato et al, 2012). Spermatogenesis is a complex process that takes place in the testis, specifically across the seminiferous tubule epithelium.…”