ESPE Abstracts

Background: Childhood obesity is a global health problem and co-morbidities develop already during childhood and adolescence. Male obesity impacts negatively on reproductive function. Testosterone is decreased, sperm quality reduced, and the physical and molecular structure of germ cells altered in obese males. However, less is known about the role of prepubertal obesity on future reproductive function. We therefore explored Leydig cell function and reproductive potential in a rat model with prepubertal onset of obesity.

Objective and hypotheses: To explore the influence of prepubertal obesity on reproductive potential and Leydig cell capacity to produce testosterone in adult male rats.

Method: Lewis male rats were exposed to high fat diet (HFD) and standard chow (SC) from day 21 until 3 (group 1) and 9 months (group 2). Various anthropometric data including fat mass and adipocyte diameter were analyzed. Mating studies and semen analyses were performed. Sex steroids and gonadotropin levels were determined by immunoassays. Testis morphology was evaluated by microscopy. Expression of Leydig cell specific genes was analyzed at the transcriptional (q-PCR) level.

Results: HFD increased body fat by 3 and 10% (P≤0.001) in groups 1 and 2 respectively. The ratio testis:body weight was reduced by 6% in group 1 but significantly (by 22%, P=0.008) in group 2 compared to SC control. Serum levels of testosterone were reduced in obese rats from group 2 (by 29%), while estradiol (E₂) was elevated in both groups of obese animals (by 44, P=0.018 and 40%, P=0.005 respectively). The decline in serum levels of testosterone in obese rats with the longest period of HFD exposure was associated with marked suppression of the expression of Leydig cell-specific genes (e.g. StAR, Cyp11a1, Hsd3b1, Hsd17b3, and Insl3).

Conclusion: Long-term obesity developed in the prepubertal period significantly affected Leydig cell capacity to produce testosterone and altered the testosterone:E₂ ratio in obese rats. Furthermore steroidogenic enzymes were down regulated. The observed perturbations of sex hormone levels may disturb normal spermatogenesis and attenuate reproductive potential and fertility in obese males.

Funding: ESPE Research Fellowship.