Melatonin actions on the spermatogonial stem cell niche in immature Syrian hamsters

RIVIERE, E; MATZKIN, ME; ROSSI SP; MAYERHOFER, A; CALANDRA RS; FRUNGIERI, MB

Barcelona

Workshop; 21st European Testis Workshop Virtual Edition; 2021

Introduction: Self-renewal and differentiation of spermatogonial stem cells (SSCs) are required to complete spermatogenesis. These processes are regulated not only by intracellular signals but also by extracellular signals secreted from the main cell populations of the SSCs niche: Sertoli cells and peritubular cells, which provide the necessary microenvironment (Mayerhofer et al. Reproduction, 145: 107, 2013). Peritubular cells are smooth-muscle-like cells with contractile function involved in the active transport of immotile sperm. Sertoli cells are essential for testicular maturation and spermatogenesis. The most important function of Sertoli cells is the provision of adequate levels of lactate to guarantee germ cell development. Both cell populations of the SSCs niche produce and secrete the glial cell line derived neurotrophic factor (GDNF), a key player responsible for self-renewal and maintenance of SSCs. Melatonin is an indoleamine that, acting through the hypothalamus and pituitary, regulates testicular function. However, direct actions of melatonin at testicular level have also been reported (Frungieri et al., Int. J. Mol. Sci. 18: 1170, 2017; Riviere et al., Mol. Cell. Endocrinol. 515: 110889, 2020). Recently, we have described a protective role of melatonin against inflammation and free radical damage in testes of patients suffering from unexplained infertility (Rossi et al. Andrology, 3: 436, 2014; Riviere et al. Mol. Cell. Endocrinol. 515: 110889, 2020).Objective: To investigate the impact of melatonin in the physiological regulation of the SSCs niche bearing in mind the critical contribution of peritubular cells on seminiferous tubules contractions and the key role of Sertoli cells supplying the energy metabolite lactate for developing spermatogenic cells.ConclusionThrough reduction of oxidative stress and stimulation of lactate production in Sertoli cells, melatonin might promote the developing of spermatogenic cells.Via its stimulatory role on peritubular cell contraction activity, this indoleamine could facilitate sperm transport.By induction of GDNF expression in both Sertoli and peritubular cells, melatonin might drive SSC self-renewal and proliferation of their direct cell progeny.Overall, this study provides insights into the potential benefits of melatonin on the SSCs niche and spermatogenic capacity.