Effects of in utero betamethasone exposure on male rats reproductive parameters, with emphasis on sperm quality and fertility: a multigenerational approach

Abstract

Glucocorticoids are potent drugs of anti-rheumatic, anti-inflammatory and immunosuppressive action, and they are the drugs of choice for antenatal treatment, promoting fetal lung maturation and thus decreasing the incidence of respiratory distress syndrome, neonatal mortality and morbidity, especially the glucocorticoid betamethasone. Studies conducted in association with our laboratory have shown that prenatal exposure to this drug promoted changes in testosterone levels and sperm parameters of male offspring. Recently, studies observed effects on the hypothalamic-pituitary-adrenal axis extending over generations. The purpose of this work is to perform comprehensive multigenerational study of possible changes in male rats reproductive parameters with emphasis on sperm quality caused by in utero exposure to betamethasone. Therefore, pregnant Wistar rats will be allocated in the control group and treated with 0.1 mg / kg betamethasone on gestational days 12, 13, 18 and 19. The male offspring of the first (F1) and second generation (F2) will be evaluated from postnatal day (PND) 30 concerning preputial separation, on PND 45: hormone levels and testicular and epididymal histomorphometry; on PND 90: hormone levels, sperm parameters, histomorphometric analysis of the testes and epididymis, immunohistochemistry for androgen receptors, sexual behavior, fertility after artificial insemination, expression levels of sperm protein SP22, pharmacological reactivity of the sex glands and ducts isolated and comet assay for detecting damage DNA. The project subject is current and very relevant, considering the wide use of this drug on therapies with maternal risk of premature delivery and due to the known action of glucocorticoids on fetal programming. This is an experimental study with translational applications. Besides generating new knowledge, we intend to prepare qualified human resources in research. (AU)