Global gene expression and morphological alterations in the mammary gland after gestational exposure to bisphenol A, genistein and indole-3-carbinol in female Sprague-Dawley offspring

GRASSI TF; ROSSI BF; MUÑOZ-DE-TORO M; BIDINOTTO LT; KASS L; DA SILVA GN; QUINALHA MM; BARBISAN LF

TOXICOLOGY AND APPLIED PHARMACOLOGY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Amsterdam; Año: 2016 vol. 303 p. 101 - 109

0041-008X

This study aimed to evaluate the modifying effects of dietary genistein (GEN)and indole-3-carbinol (I3C) on early mammary gland development in female Sprague-Dawley offspring born to mothers exposed to BPA during gestation. Pregnant rats weretreated with BPA 25 or 250ug/kg bw/day from gestational day 10 to 21 with or withoutdietary intake of GEN (250 mg/kg chow) or I3C (2000 mg/kg chow). At post-natal day(PND) 21, female offspring from different litters were euthanized for mammary glanddevelopment and gene expression analyses. Our results indicated that prenatal exposureto BPA25 and 250 did not modify the ductal elongation of the mammary gland tree orthe estrogen receptor alpha (ER-a) expression in terminal end buds (TEBs). However,BPA25-exposed offspring had a higher number of terminal structures (TEBs+TDs) andan increased mammary branching and cell proliferation index in TEBs. Besides that,BPA25 and 250 modulated the expression of several genes in the immature mammarygland that were not changed in a dose dependent manner and involved different clustersof up- and down-regulated genes. Furthermore, BPA25 and BPA250+I3C-treatedgroups also had a higher number of enriched functional gene categories. In addition,maternal dietary GEN and I3C in association with BPA exposure produced specificgene expression alterations in the mammary gland and overcome the adverse effect ofBPA25, decreasing the branching of the mammary gland. In conclusion, prenatal BPAexposure induced both morphological and gene expression modifications on themammary gland that dietary intake of GEN and I3C reverted on BPA 25-exposedanimals.