Development and steroidogenic capacity of adult Leydig cell population in experimental conditions of hyperglycemia and obesity

Introduction and Aim: The metabolic syndrome involves various abnormalities like obesity, insulin resistance/ diabetes, hypertension, and hormonal disorders. It is a serious risk factor for male infertility, often associated with compromised hypothalamic-pituitary-gonadal axis. The aim of the present study was to evaluate adult Ley­dig cell (LC) number and steroidogenesis in tandem with macro biomarkers (body and testis weight, fat accumu­lation) in experimental conditions of diabetes mellitus (DM) induced on day 1 (neonatally, NDM) or day 10 (pre­pubertally, PDM); short- and long-term high-fat diet (HFD) with induced obesity in rats since puberty. Results: Significant increase was established in body weight and body fat in short- and long-term HFD. It was as­sociated with a decrease in relative testicular weight in long-term HFD (gonado-somatic index). Epididymal and inguinal adipocyte diameters were increased in the animals from both groups. HFD did not affect significantly serum testosterone and LH levels. Nevertheless, expression of LC key steroido­genic factors and intratesticular testosterone levels were significantly lower in long-term HFD rats, associated with a reduction of the LC number. Hyperglycaemia was confirmed by a significant elevation of blood glucose levels by 15% in adult NDM and by 35% in PDM rats. In NDM body weight and testicular weight were increased but the gonado-somatic index was de­creased by 15%. PDM rats had normal body weight but the testicular weight and gonado-somatic index were de­creased by 30%. Leydig cell number and testosterone production were in normal range in adult NDM, whereas they were significantly decreased in PDM. Conclusion: Our results from the HFD experimental model demonstrated that long-term HFD influenced nega­tively the number of Leydig cells and testosterone production. Prepubertal DM, but not neonatal DM, suppressed Leydig cell development and steroidogenesis in adulthood. Altogether, our data indicated that diabetes and obe­sity affected the size of adult Leydig cell population and testicular steroidogenic function and they were associat­ed with reduced macroparameters - body weight, absolute and relative testicular weight.