Efeitos da exposição pré-natal a glicocorticoide sintético no desenvolvimento do testículo de camundongos

Abstract

Glucocorticoids, in the prenatal period, promote the maturation of the lungs and the development of systems in the fetus body, with that, they are routinely used as a treatment for preterm labour. However, prenatal exposure to synthetic GC can induce inhibitory responses in the testes. Knowing the importance of glucocorticoids in reproductive functions, our goal is to describe the role of GC in the morphofunctional regulation of the testis in neonatal (1 pnd), pubertal (35 pnd) and adult mice (70 pnd), and sperm parameters, using a clinical dose of 0.4mg/Kg of Dexamethasone (DEX 0.4) and an overdose of 5mg/Kg of Dexamethasone (DEX 5) in a single dose at 15,5 embryonic days, that represents the period of the masculinization programming window. The control group did not undergo any manipulation. Were evaluated the testicular and adrenal gland histomorphometry, the expression of steroidogenic enzymes by RT-PCR and the sperm parameters. It was demonstrated that, in neonatal animals, there is a decrease in the germinal epithelium in DEX 0.4 group compared to DEX 5 and that pattern remained in adult animals, despite the increase in all parameters in the treated puberal individuals, indicating an advance in puberty. Furthermore, an increase in the meiotic index and a decrease in the apoptotic index were observed in the group that received the highest dose of Dexamethasone. Regarding the interstitial compartment, in neonates there was a tendency towards a decrease in Leydig cell parameters in DEX 5 group, while in puberal and adult animals there was an increase in the nuclear, cytoplasmic, and cellular volume of this same group. Probably, fetal and adult Leydig cells present different responses to glucocorticoids in the prenatal period. The adrenal gland did not show significant differences in area and volume, however, qualitatively, they presented different effects on the glandular architecture from the treated groups compared to the control. Also, no significant differences were observed in the expression of the genes evaluated through RT-PCR. However, the levels of INSL3 were repressed in DEX0,4 while unexpressed in DEX5. However, sperm concentration increased in DEX 0,4 and DEX 5 groups, as well as morphological changes, mainly in head and tail defects. Furthermore, an increase in DNA fragmentation was observed in mice treated with the highest dose of Dexamethasone, indicating that the increase in concentration is not related to better quality. Thus, taken together, our data indicate that glucocorticoids have a strong regulatory role in testicular function and can induce chances in long-term fertility.