Leptin and Sertoli cells mitochondrial bioenergetics

• Autor(a) principal: Moreira, Bruno Manuel Pereira
• Data de Publicação: 2017
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.6/6727
• topic: Células de Sertoli; Espermatogénese; Infertilidade; Leptina; Mitocôndria.; Obesidade; Domínio/Área Científica::Ciências Médicas::Ciências Biomédicas

Metabolic diseases, such as obesity, stand as one of the greatest challenges of the 21st century. Obesity in reproductive-age men has risen and is expected to continue to increase. In an inverse direction, fertility is decreasing in those men and it largely contributes for the high demand of fertility treatment by couples in modern societies. The male factor alone or in combination with female factor is present in 1/3 of the couples seeking for fertility treatment. In fact, sperm parameters are on a downward spiral during the last decades reaching worrying levels. In overweight and obese individuals, there is a hormonal dysfunction, particularly in leptin levels that are heavily increased. Besides the well-described functions at the hypothalamic level, leptin acts in several peripheral tissues. Although leptin has been on spotlight since its discovery, its effects in the male reproductive tract, particularly on Sertoli cells (SCs), remain unknown. More recently, leptin has shown the ability to modulate mitochondrial dynamics, biogenesis and functioning in several cellular systems, including cancer cells. Herein, we studied the effects of leptin in the proliferation and metabolic activity of rat Sertoli cells (rSCs). We also evaluated the effects of leptin in mitochondria physiology, particularly in the levels of mitochondrial complexes, messenger RNA (mRNA) levels of mitochondrial biogenesis markers and mitochondrial membrane potential. For comparative purposes, and taking in consideration previous results from the group, we also studied the effects of leptin in mRNA levels of mitochondrial biogenesis markers and mitochondrial complexes in human Sertoli cells (hSCs). Our results suggest that leptin modulates the metabolic activity and mitochondrial function in rSCs after exposure to a concentration of 50 ng/mL, which mimics a concentration found in morbidly obese men. These findings suggest that high concentrations of leptin, such as those found in morbidly obese individuals, modulate mitochondrial function in rSCs, which could represent a novel mechanism through which leptin contributes to obesity-induced subfertility or infertility in males. Interestingly, leptin exposure had no effect in several aspects of mitochondria physiology, such as mRNA levels of mitochondrial biogenesis markers and levels of mitochondrial complexes which further indicates that leptin seems to affect mitochondrial function. In hSCs, the mRNA levels of Sirtuin 1 (SIRT1) presented changes in the group treated with 50 ng/mL of leptin. Protein levels of mitochondrial complex II presented changes in the groups treated with 5 and 50 ng/mL of leptin while in rSCs no differences were observed. Thus, rSCs and hSCs seem to be differently affected by leptin exposure. These differences, particularly in SIRT1 mRNA levels, are species-dependent and may represent a novel mechanism through which leptin affects the metabolic control of spermatogenesis and thus, with implications in hSCs.