ESPE Abstracts (2022) 95 P1-172

ESPE2022 Poster Category 1 Sex Differentiation, Gonads and Gynaecology, and Sex Endocrinology (56 abstracts)

Diabetes type 1 can induce testicular atrophy with Leydig cell hyperplasia and germ cell depletion and therefore prevents reproductive function and fertility in rats

Isabel Viola Wagner 1,2 , Nora Kloeting 3,4 , Alexandra Kulle 5 , Karen Rieck 1 , Olle Söder 2 & Olaf Hiort 1


1Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics, University of Lübeck, Lübeck, Germany; 2Paediatric Endocrinology Unit, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden; 3Integrated Research and Treatment Center (IFB Adiposity Diseases), Department of Medicine, University of Leipzig, Leipzig, Germany, Leipzig, Germany; 4Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig, Leipzig, Germany; 5University Hospital Kiel, Hormone Center for Paediatric Endocrinology Laboratory, Kiel, Germany

Research Aim: Diabetes type 1 can negatively influence testicular function and fertility but the pathomechanisms on the testicular level remain to be elucidated. Therefore, the aim of the study was to evaluate effects of diabetes mellitus type 1 disease on testicular function.

Material and Methods: BB/OKL rats developed type 1 diabetes during adolescence. Rats were treated with different Insulin implants to achieve sufficient and insufficient HbA1c levels. Leydig-, Sertoli-, and germ-cell function was analysed on RNA and protein level. Testosterone, androstendione and dihydrotestosterone were measured in serum samples and intratesticular with LCMSMS. Immunhistochemistry and functional analysis were performed, including the evaluation of apoptosis, inflammation and oxidative stress.

Results: After diabetes manifestation 25-33% of the rats developed testicular atrophy. In the atrophic testis, we found a strong reduction of elongated and round spermatids and spermatocytes by more than 80%. Leydig cells showed a hyperplasia with a strong and significant upregulation of steroidogenic enzymes on RNA and on protein level (Star by 106%/94%, 3Beta-HSD by 177%/203%, 17Beta-HSD by 276%/134%, CYP11A1 by 66%/65% and CYP17A1 by 1859%/2202%). Furthermore, we measured higher concentrations of androgens and INSL3 levels in the atrophic testis. In contrast, germ cells showed a depletion with a strong downregulation of DDX4 and Crem. In addition, we found a strong increase of oxidative stress, apoptosis and inflammation. SF-1 and DHH pathways were strongly upregulated in the atrophic testis and might me a possible pathomechanism.

Conclusion: Diabetes type 1 can induce testicular atrophy by germ cell depletion, apoptosis and increased inflammation. In parallel, Leydig cell hyperplasia develops with an upregulation of steroidogenic enzymes, and higher intratesticular testosterone levels. Therefore, diabetes type 1 can negatively influence reproductive function and fertility in male rats.

Volume 95

60th Annual ESPE (ESPE 2022)

Rome, Italy
15 Sep 2022 - 17 Sep 2022

European Society for Paediatric Endocrinology 

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