Long-term adverse effects on reproductive function in male rats exposed prenatally to the glucocorticoid betamethasone.

Betamethasone is the drug of choice for antenatal treatment, promoting fetal lung maturation, decreasing the incidence of respiratory distress syndrome and neonatal mortality. Previous studies reported that prenatal treatment with this drug reduced testosterone levels, sperm quality and fertility in adult rats. We aimed to further evaluate the reproductive consequences of prenatal betamethasone exposure in male rats. Pregnant Wistar rats (n=13/group) were separated into two groups: control (vehicle) and betamethasone- treated (0.1mg/kg IM) and rats were injected on gestational days 12, 13, 18 and 19. Body weight, sexual behavior, reproductive organ weights, serum hormone levels, accessory glands contractility, sperm parameters, and fertility after in utero artificial insemination were evaluated. Our results showed that prenatal betamethasone exposure provoked a significant reduction in body weight at PND 01 and, at adulthood, decrease in FSH levels, sperm motility and production. Furthermore, seminal vesicle weight was decreased while testicular and ventral prostate weights were increased. Serum LH levels and the percentage of abnormal sperm were significantly increased. Although sexual behavior was not altered, a significant reduction in fertility in the adult rats exposed prenatally to betamethasone was noted. We concluded that prenatal betamethasone exposure leads to long-term reproductive impairment in male rats. These results may have important implications for humans, considering the use of this glucocorticoid in pregnant women.

Alterations in male rats following in utero exposure to betamethasone suggests changes in reproductive programming.

Antenatal betamethasone is used for accelerating fetal lung maturation for women at risk of preterm birth. Altered sperm parameters were reported in adult rats after intrauterine exposure to betamethasone. In this study, male rat offspring were assessed for reproductive development after dam exposure to betamethasone (0.1mg/kg) or vehicle on Days 12, 13, 18 and 19 of pregnancy. The treatment resulted in reduction in the offspring body weight, delay in preputial separation, decreased seminal vesicle weight, testosterone levels and fertility, and increased testicular weight. In the testis, morphologically abnormal seminiferous tubules were observed, characterized by an irregular cell distribution with Sertoli cell that were displaced towards the tubular lumen. These cells expressed both Connexin 43 (Cx43) and Proliferative Nuclear Cell Antigen (PCNA). In conclusion, intrauterine betamethasone treatment appears to promote reproductive programming and impairment of rat sexual development and fertility due to, at least in part, unusual testicular disorders.

In utero and lactational exposure to fipronil in female rats: Pregnancy outcomes and sexual development.

Fipronil, a phenylpyrazole insecticide, is used in agriculture, veterinary medicine, and public health. Because this insecticide is considered a potential endocrine disruptor, the aim of this study was to examine the influence of perinatal exposure to fipronil on neonatal female reproductive system development. Pregnant rats were exposed (via gavage) daily to fipronil (0.03, 0.3, or 3 mg/kg) from gestational day 15 to day 7 after birth, and effects on the reproductive functions assessed on postnatal day (PND) 22. No signs of maternal toxicity were observed during daily treatment with fipronil. Perinatal exposure to the highest dose of fipronil (3 mg/kg) delayed the age of vaginal opening (VO) and first estrus without markedly affecting the anogenital distance (AGD). Further, exposure to 0.3 mg/kg fipronil produced a significantly shorter estrus cycle and reduced number of cycles during the period of evaluation. However, the other reproductive parameters analyzed, including fertility, hormone levels, sexual behavior, and histology of ovaries and uterus, displayed no marked alterations. In this experimental model, fipronil interfered with development of neonatal female reproductive system as evidenced by delay in VO and estrus cycle alterations without apparent significant effects on fertility. Further studies are needed to identify the mechanisms of action associated with the observed female reproductive system changes.