Exposure to manganese during sertoli cell formation and proliferation disturbs early testicular development in rats.

Manganese (Mn) is a metal and important micronutrient. However, exposure to supraphysiological levels of Mn, which occur through fungicides, atmospheric emissions, drainages, and spills, has been related to health risks, including morphometric changes in the male reproductive organs and impairment on gametogenesis and sperm quality, impacting the fertile ability of adult animals. Despite the relevance of the fetal/perinatal period for toxicological studies on Mn, previous data only deal with the physical and neurological development of the offspring, without mentioning their reproductive development. The present study investigated whether exposure to Mn during fetal/perinatal phase, specifically during the period of formation and proliferation of Sertoli cells, impairs the reproductive development of male offspring in early postnatal life. Therefore, pregnant Wistar rats were randomly distributed into 3 experimental groups: Ctl (received saline solution), Mn-9 (received 9 mg/kg of MnCl2), and Mn-90 (received 90 mg/kg of MnCl2). The female rats received the experimental treatment by gavage from gestational day 13 to lactational day 15, i.e., postnatal day (PND) 15 of the pups. Oxidative damage to the genetic material of germ and Sertoli cells, together with a decrease in connexin 43 immunolabeling were observed in the testis of male pups evaluated at PND 15. In addition, an increase in the seminiferous tubules presenting slight epithelium vacuolization and cells with eosinophilic cytoplasm were observed, without apparent epididymal changes. In conclusion, it was demonstrated that Mn perturbed the initial testicular development by altering Sertoli cell integrity through oxidative insult, which may compromise the spermatogenesis in the long-term.

Impact of intrauterine exposure to betamethasone on the testes and epididymides of prepubertal rats.

Therapy with betamethasone, a synthetic glucocorticoid, is used in cases of preterm birth risk, in order to promote fetal lung maturation, and decrease neonatal mortality and morbidity. However, late reproductive disorders related to the prenatal exposure to this compound have been reported by our Laboratory, in both male and female rats. Thus, the present study aimed to evaluate the impact of betamethasone on postnatal reproductive development, during pre-puberty, of male offspring exposed in utero to this synthetic glucocorticoid. For this purpose, pregnant Wistar rats were allocated into two groups: Control, treated with saline, and the group treated with betamethasone at 0.1 mg/kg/day. Control and betamethasone groups were treated with intramuscular injection on gestational days 12, 13, 18 and 19, critical days of prenatal reproductive development. The treatment is associated with reduced body and organ weights, disorders in initial reproductive parameters of pre-pubertal male offspring exposed in utero to betamethasone, such as reduction of anogenital distance, alterations in histomorphometric parameters and immunostaining pattern of androgen and estrogen receptors on testicles and epididymides. Our results suggest that prenatal exposure to betamethasone potentially causes reproductive reprogramming and impairs male postnatal reproductive development. This data raise concerns about the use of betamethasone for human antenatal therapy.