Impacto da exposição perinatal de desreguladores endócrinos ambientalmente relevantes sobre a foliculogênese e remodelamento ovariano de ratas adultas

Abstract

Endocrine disruptors (EDs) are chemical substances ubiquitous in the human and animal environment that can disrupt the endocrine system and affect reproductive processes such as ovarian folliculogenesis. In this study, we investigated the effects of a mixture of endocrine disruptors (ED -mix) based on human environmental exposure on ovarian folliculogenesis and ovarian tissue organization in adult rats whose mothers were exposed to this mixture during gestation and lactation. To achieve this objective, pregnant females of the Sprague-Dawley line were randomly divided into two experimental groups: (i) the control group (Control), which received an oral administration of 2ml/kg corn oil, and (ii) the ED mix group, which received an oral administration of 32.11mg/kg/day of a mixture of twelve compounds (phthalates, pesticides, UV filters, bisphenol A, butylparaben) diluted in 2ml/kg corn oil Pregnant and lactating rats were treated from gestational day 7 (GD7) to postnatal day 21 (DPN21). After weaning, on PND22, there was a pause in the induction of mixtures of these compounds, and the females of the F1 offspring were sacrificed on postnatal day 360. The ovaries were removed, dissected, and examined histologically. Blood samples were also taken from the animals to determine hormone levels of estradiol and progesterone. Hematoxylin-eosin and picrosirius-stained tissue sections were examined for morphologic characteristics, measurement of fractal dimension, and quantification of total collagen, including type I and III fractions. The effects of exposure to the ED mixture during the fetal and lactation periods were assessed by Student's T test, with differences considered significant at P≤ 0.05. The results indicate that the mixture of endocrine disruptors led to an increase in the proportion of type I collagen fibers and III, a decrease in the number of follicles and corpora lutea, and a decrease in serum levels of 17β-estradiol and progesterone in F1-generation females. Overall, these results highlight that multigenerational exposure contributes to ovarian fibrosis in F1 generation rats and impairs antral follicle development, ovulatory capacity, and corpus luteum formation.