Artículo
Bisphenol A and benzophenone-3 exposure alters milk protein expression and its transcriptional regulation during functional differentiation of the mammary gland in vitro
Altamirano, Gabriela Anahí
; Gomez, Ayelen Luciana
; Schierano Marotti, Gonzalo; Muñoz de Toro, Monica Milagros; Rodriguez, Horacio Adolfo
; Kass, Laura
Fecha de publicación:
12/2020
Editorial:
Academic Press Inc Elsevier Science
Revista:
Environmental Research
ISSN:
0013-9351
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
The plastic monomer and plasticizer bisphenol A (BPA), and the UV-filter benzophenone-3 (BP3) have been shown to have estrogenic activities that could alter mammary gland development. Our aim was to analyze whether BPA or BP3 direct exposure affects the functional differentiation of the mammary gland using an in vitro model. Mammary organoids were obtained and isolated from 8 week-old virgin female C57BL/6 mice and were differentiated on Matrigel with medium containing lactogenic hormones and exposed to: a) vehicle (0.01% ethanol); b) 1 × 10−9 M or 1 × 10−6 M BPA; or c) 1 × 10−12 M, 1 × 10−9 M or 1 × 10−6 M BP3 for 72 h. The mRNA and protein expression of estrogen receptor alpha (ESR1) and progesterone receptor (PR) were assessed. In addition, mRNA levels of PR-B isoform, glucocorticoid receptor (GR), prolactin receptor (PRLR) and Stat5a, and protein expression of pStat5a/b were evaluated at 72 h. The mRNA and protein expression of milk proteins and their DNA methylation status were also analyzed. Although mRNA level of PRLR and GR was similar between treatments, mRNA expression of ESR1, total PR, PR-B and Stat5a was increased in organoids exposed to 1 × 10−9 M BPA and 1 × 10−12 M BP3. Total PR expression was also increased with 1 × 10−6 M BPA. Nuclear ESR1 and PR expression was observed in all treated organoids; whereas nuclear pStat5a/b alveolar cells was observed only in organoids exposed to 1 × 10−9 M BPA and 1 × 10−12 M BP3. The beta-casein mRNA level was increased in both BPA concentrations and 1 × 10−12 M BP3, which was associated with hypomethylation of its promoter. The beta-casein protein expression was only increased with 1 × 10−9 M BPA or 1 × 10−12 M BP3. In contrast, BPA exposure decreased alpha-lactalbumin mRNA expression and increased DNA methylation level in different methylation-sensitive sites of the gene. Also, 1 × 10−9 M BPA decreased alpha-lactalbumin protein expression. Our results demonstrate that BPA or BP3 exposure alters milk protein synthesis and its transcriptional regulation during mammary gland differentiation in vitro.
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(ISAL)
Articulos de INSTITUTO DE SALUD Y AMBIENTE DEL LITORAL
Articulos de INSTITUTO DE SALUD Y AMBIENTE DEL LITORAL
Citación
Altamirano, Gabriela Anahí; Gomez, Ayelen Luciana; Schierano Marotti, Gonzalo; Muñoz de Toro, Monica Milagros; Rodriguez, Horacio Adolfo; et al.; Bisphenol A and benzophenone-3 exposure alters milk protein expression and its transcriptional regulation during functional differentiation of the mammary gland in vitro; Academic Press Inc Elsevier Science; Environmental Research; 191; 12-2020; 1-14
Compartir
Altmétricas