Current lifestyle, characterized by physical inactivity and a poor diet, is heavily linked with an increased incidence of metabolic diseases. One of the most serious silent co-morbidities of those diseases is infertility. The hormonal link between food intake and energy homeostasis is mediated by the leptin ghrelin axis. Compelling evidence suggests that direct leptins action regulates cellular glucose homeostasis and mitochondrial biogenesis. We have recently shown that leptin modulates the nutritional support of spermatogenesis, which may be related with obesity-related male subfertility/infertility. Herein, we hypothesized that leptin directly affects mitochondrial function, dynamics and biogenesis of Sertoli cells (SCs). Rat Sertoli cells (Ser-W3) were treated (n=5 for each group), during 24 h at 37°C 5% CO2, with different concentrations of leptin (5 ng/ml as reported in normal mice, 25 ng/ml as reported in obese mice and 50 ng/ml as a supraphysiological concentration) and the results were compared to a condition without leptin. Western Blot was performed to determinate protein levels of mitochondrial complexes. qPCR was performed to determinate expression levels of several genes involved in mitochondrial biogenesis and to assess mitochondrial DNA copy number. Mitochondrial membrane potential was determined by JC-1. Direct leptin exposure did not alter SCs proliferation rate, though all leptin concentrations decreased SCs metabolic activity. That was accompanied with alterations in the expression levels of the different mitochondrial complexes and also of genes involved in mitochondrial biogenesis. In addition, the highest concentration of leptin decreased mitochondrial membrane potential. Finally, mitochondrial DNA copy number was not sensitive to the treatment with the different leptin concentrations. Overall, the results show a direct action of leptin on Sertoli cells mitochondrial function and biogenesis with implications in the nutritional support of spermatogenesis, which is a novel mechanism by which leptin can affect the reproductive potential of males.
20 - 23 May 2017
European Society of Endocrinology