Type 1 diabetes mellitus (T1DM) is associated with impaired spermatogenesis, lower testosterone levels and epididymal weight. However, the underlying processes in the testis are unknown and remain to be elucidated. Therefore, the present study focused on the effects of T1DM on testicular function in a spontaneously diabetic rat model.BB/OKL rats after diabetes manifestation were divided into three groups: without insulin treatment, insulin treatment for a duration of 2 and of 6 weeks. Anthropometrical data, circulating levels of gonadotrophins, testosterone and inhibin B were measured. Intratesticular testosterone, oxidative stress, inflammation, and apoptosis were analyzed. Key enzymes of steroidogenesis were evaluated in the testis.Untreated diabetic rats had significantly lower serum FSH and LH levels. Serum and intratesticular testosterone levels significantly decreased in the untreated diabetic rat compared to healthy controls. Key markers of Leydig cell function were significantly downregulated on RNA level: Insl3 by 53% (p=0.006), Star by 51% (p=0.004), Cyp11A1 by 80% (p=0.003), 3Beta-Hsd2 by 61% (p=0.005) and Pbr by 52% (p=0.002). In the insulin-treated group only Cyp11A1 and 3Beta-Hsd2 transcripts were significantly lower. Interestingly the long-term insulin treated group showed significant upregulation of most steroidogenic enzymes without affecting testosterone levels. TNF-alpha and apoptosis were significantly increased in the long-term insulin treated rats. In conclusion T1DM, with a severe lack of insulin, has an adverse action on Leydig cell function. This is partially reversible with well compensated blood glucose control. Long-term T1DM adversely affects Leydig cell function due to the process of inflammation and apoptosis.
Institute(s)Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
GrantsIFB Adiposity Diseases Federal State of Saxony Deutsche Forschungsgemeinschaft European Society for Pediatric Endocrinology (ESPE Research Fellowship) Stiftelsen Samariten Sallskapet Barnavard Kronprinsessan Lovisas Foundation Frimurare Barnhuset Foundation European Union's Horizon 2020 research and innovation programme