Reproductive disorders in female rats after prenatal exposure to betamethasone

Abstract

Betamethasone is the drug of choice for antenatal treatment, promoting fetal lung maturation and decreasing mortality. Previous studies in rats reported male programming and alteration in sperm parameters and sexual behavior following intrauterine betamethasone exposure. The impact on the female reproductive development is not known. In this study, rat female offspring was assessed for sexual development, morphophysiology of the reproductive tract and fertility after maternal exposure to 0.1 mg kg of betamethasone or vehicle on gestational days 12, 13, 18 and 19. The treatment promoted reduction of litter weight on postnatal day 1, morphological masculinization in females, delay in the age of puberty onset, reduction in estrus number, increase in estrous cycle length and increase in luteinizing hormone serum levels and uterus weight. The females from the betamethasone group showed an increase of myometrial uterine area and decrease in endometrial uterine area. These animals also performed less lordosis during the sexual behavior test and showed impaired reproductive performance. The uterus showed higher contraction in the treated group as shown by a pharmacological assay. In conclusion, prenatal betamethasone exposure in rats promoted female masculinization, altered sexual development and reproductive parameters. Copyright © 2017 John Wiley & Sons, Ltd.

Reproductive disorders in female rats after prenatal exposure to sodium arsenite

“…Herein, corroborating with reproductive organs weight we did not find alteration in ovarian morphology and number of follicles and corpora lutea in females exposed to arsenic. Similar results were also found in female rats prenatally exposed to di-n-butyl-phthalate and betamethasone that also act as endocrine disruptors (Borges et al, 2017;Guerra et al, 2010). In the uterus, on the other hand, an increase was observed in endometrium, myometrium and perimetrium areas in arsenic-exposed females, despite their normal organ weight and tissue morphology.…”

“…Several works have shown that in utero exposure to stressors, glucocorticoids and endocrine disruptors induce masculinization in female offspring (Borges et al, 2017;Guerra, Silva, Luchiari, Sanabria, & Kempinas, 2014;Wolf et al, 2002), which might be confirmed by AGD measurement, nipple count and body weight evaluation (Gallavan et al, 1999;Wolf et al, 2002). Herein, the increase in relative AGD indicates female masculinization in the offspring of the sodium arsenite group, despite unchanged nipples count.…”

“…The experimental period adopted here corresponds to the embryonic period and all intrauterine fetal development of rats,and has been previously used in studies evaluating the effects of prenatal exposure to toxicants in reproductive tract development (Kozul-Horvath et al, 2012;Li et al, 2018). For each analysis, one or two female rats from each litter were used to avoid variation due to litter effects (Borges et al, 2017). This dose, in turn, is faced by humans in the main arsenic-affected areas in the world (Mukherjee et al, 2006).…”

“…The pups were weaned at PND 21 and housed in separate cages (n = 3 females). For each analysis, one or two female rats from each litter were used to avoid variation due to litter effects (Borges et al, 2017). Male pups were assigned to another study.…”

“…Currently, humans have been constantly exposed to a wide variety of environmental pollutants from natural and anthropogenic sources (Alias et al, 2019;Ma et al, 2019). Some of these toxic agents might act as endocrine disruptors, inducing different health effects (Borges et al, 2017;Choi, Yoo, & Lee, 2004;Guerra, Scarano, Toledo, Franci, & Kempinas, 2010;Paumgartten, 2003). They can interfere with the production, release and metabolism of hormones that are crucial for development and body homeostasis (Kopp, Martínez, Legradi, & Legler, 2017).…”