Quantitative evaluation of Leydig cell number and steroidogenesis in tandem with spermatogenic macro-parameters following experimentally induced diabetes mellitus and obesity in rat

Abstract

Metabolic syndrome (MetS) is global health problem that impacts negatively more than 20-25% of human population inducing various abnormalities like obesity, insulin resistance/diabetes, hypertension and hormonal disorders. The MetS is serious risk factor for male infertility being often associated with compromised hypothalamic-pituitary-gonadal axis that affects sperm count, sperm quality and testosterone production by the testis. The cellular and molecular mechanisms underlying testicular dysfunction in condition of metabolic disorders are poorly understood.The aim of the present study was to evaluate Leydig cell number and steroidogenesis in tandem with investigation of macro-parameters of spermatogenesis in experimental conditions of diabetes mellitus (DM) induced on day 1 (neonatally) or day 10 (prepubertally) and high-fat diet (HFD) induced obesity in adult rats.Spermatogenic macro-parameters investigated were: 1) percentage volume (%Vol) of the lumen of seminiferous tubules as an indicator of Sertoli cell function to secrete seminal fluid; 2) %Vol of seminiferous epithelium. Our data from stereological analysis on day 25th (mid puberty) and on day 60th (adulthood) revealed insignificant decrease in luminal percent volume in all diabetic rats. These finding were associated with higher %Vol of seminiferous epithelium probably due to increased %Vol of cell cytoplasm. In adult rats that were fed on HFD we established increased serum levels of estradiol and leptin. We have found that obesity state inhibited the expression of key steroidogenic factors (StAR and Cyp11a1) associated with low levels of intratesticular testosterone and reduced number of Leydig cells.All together, our data indicate that diabetes and obesity may affect testicular function via alteration in somatic cells of the testis - Sertoli cells in the seminiferous epithelium and Leydig cells in the interstitium.