Environmental estrogens exposure alters milk proteins synthesis and their transcriptional regulation during mammary gland in vitro differentiation

ALTAMIRANO GA; RODRIGUEZ HA; MUÑOZ-DE-TORO M; GOMEZ AL; KASS L

Buenos Aires

Congreso; Xth Meeting of the Latin American Society for Developmental Biology; 2019

Latin American Society for Developmental Biology

There are several human-made chemical compounds with hormonal action.Among them, the plastic monomer and plasticizer Bisphenol A (BPA), and theUV-filter benzophenone-3 (BP3) have been shown to have estrogenic activities.Our aim was to study the effects of BPA or BP3 exposure on the mammarygland functional differentiation using an in vitro model. Mammary organoidswere obtained and isolated from 8 weeks-old C57BL/6 female mice using anenzymatic/mechanical digestion. The organoids were cultured on Matrigel withgrowth medium for 24 hs. Then, the medium was changed to a differentiationone (with prolactin) and exposed to: a) vehicle (0.01% ethanol), b) 10-9or 10-6MBPA or c) 10-12 to 10-6M BP3 for 72 hs. Milk proteins expression and their DNAmethylation (DNAme) status were evaluated. Regarding beta-casein (CSN2)expression, its mRNA level was augmented in both BPA concentrations and 10-12M BP3; and this result was associated with hypomethylation of its promoter.Despite this, its protein expression was increased only in mammary organoidsexposed to 10-9M BPA or 10-12M BP3. In contrast, BPA exposure showed adecrease of alpha-lactoalbumin (LALBA) mRNA expression and an increase ofDNAme status in different methylation-sensitive sites of the gene. Also,10-9MBPA induced a decrease of LALBA protein expression. Our results demonstratethat BPA or BP3 direct exposure alters milk protein synthesis and itstranscriptional regulation during mammary gland in vitro differentiation.