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.