Effect of voluntary exercise and insulin glargine administration in rats with gestational diabetes on apelin- 13 serum level, its receptor gene expression in testis, pituitary-gonadal axis function and histological- stereological changes in male offspring

Abstract

Despite the evidence that gestational diabetes mellitus (GDM) is associated with reproductive dysfunction in offspring, the cellular mechanisms involved are not exactly clear. This study aimed to investigate the effect of voluntary exercise and insulin glargine in pregnant mothers with GDM on metabolic and reproductive disorders in first-generation male offspring. Methods: 50 female Wistar rats (three weeks old) received a standard diet (n=10) or a high-fat-sucrose diet (n=40) for 6 weeks before mating. After mating and confirmation of pregnancy, blood glucose was measured daily, and GDM was defined as blood glucose greater than 140 mg/dL from day 7 of pregnancy onwards. Then the animals were randomly divided into subgroups of control, GDM, GDM + voluntary exercise, GDM + insulin glargine (5-7 units per day, subcutaneous, until the end of pregnancy) and GDM + voluntary exercise and insulin glargine together. Voluntary exercise was done by placing animals in special cages with a rotating wheel. To assess insulin resistance, a glucose tolerance test (GTT) was performed on the 15th day of pregnancy. 3 weeks after birth, the male offspring were weaned and fed with a standard diet until 12 weeks of age. At the end of the study, lipid profile was evaluated by spectrophotometric method, and serum level of LH, FSH, testosterone, and apelin-13 hormones were evaluated by ELISA kit. Aplin-13 (APJ) mRNA expression in male testes tissue was investigated using real-time PCR method. In addition, evaluation of stereology and histology of testicular tissue was done and sperm parameters were investigated. Results: The findings of the present study showed that treatment with voluntary exercise and insulin glargine alone and in combination in mothers with GDM improved lipid profile, significantly decreased FSH and LH and apelin-13 serum levels, significantly increased testosterone and apelin receptor (APJ) expression in offspring. Furthermore, mono therapy and combination therapy were able to significantly increase the viability and quality of sperm motility and the number of Leydig cells, significantly decrease the sperm deformity index and the percentage of sperm with damaged DNA and the teratozoospermia index and abnormal condition in different parts of sperm in offspring of mothers with GDM. In all measured parameters, the effect of combined treatment was better than monotherapies. Combined treatment also improved the stereological changes caused by maternal diabetes in the testes, although the result was not statistically significant.