Prenatal Bisphenol A Exposure Induces Preneoplastic Lesions in the Mammary Gland in Wistar Rats

Overview

Journal Environ Health Perspect

Date 2007 Mar 21

PMID 17366824

Citations 112

Authors

Milena Durando

Laura Kass

Julio Piva

Carlos Sonnenschein

Ana M Soto

Enrique H Luque

Monica Munoz-de-Toro

Affiliations

Soon will be listed here.

Abstract

Background: Humans are routinely exposed to bisphenol A (BPA), an estrogenic compound that leaches from dental materials, food and beverage containers, and other consumer products. Prenatal exposure to BPA has produced long-lasting and profound effects on rodent hormone-dependent tissues that are manifested 1-6 months after the end of exposure.

Objective: The aim of the present work was to examine whether in utero exposure to BPA alters mammary gland development and increases its susceptibility to the carcinogen N-nitroso-N-methylurea (NMU).

Methods: Pregnant Wistar rats were exposed to BPA (25 pg/kg body weight per day) or to vehicle. Female offspring were sacrificed on postnatal day (PND) 30, 50, 110, or 180. On PND50 a group of rats received a single subcarcinogenic dose of NMU (25 mg/kg) and they were sacrificed on either PND110 or PND180.

Results: At puberty, animals exposed prenatally to BPA showed an increased proliferation/apoptosis ratio in both the epithelial and stromal compartments. During adulthood (PND110 and PND180), BPA-exposed animals showed an increased number of hyperplastic ducts and augmented stromal nuclear density. Moreover, the stroma associated with hyperplastic ducts showed signs of desmoplasia and contained an increased number of mast cells, suggesting a heightened risk of neoplastic transformation. Administration of a subcarcinogenic dose of NMU to animals exposed prenatally to BPA increased the percentage of hyperplastic ducts and induced the development of neoplastic lesions.

Conclusions: Our results demonstrate that the prenatal exposure to low doses of BPA perturbs mammary gland histoarchitecture and increases the carcinogenic susceptibility to a chemical challenge administered 50 days after the end of BPA exposure.

Citing Articles

Short-Term Exposure of Bisphenol A Deteriorates the Quality of Rabbit Milk by Impairing Milk Fat Synthesis.

Hao J, Beng S, Ma Z, Xu H, Yang T, Yang Q Food Sci Nutr. 2024; 12(12):10666-10679.

PMID: 39723079 PMC: 11666964. DOI: 10.1002/fsn3.4561.

Maternal Bisphenol B Exposure and Mammary Gland Development of Offspring: A Time-Series Analysis.

Ji X, Jiang P, Li Y, Su L, Yue H, Sang N Environ Health (Wash). 2024; 1(4):278-290.

PMID: 39474496 PMC: 11504573. DOI: 10.1021/envhealth.3c00085.

The Conflict between Regulatory Agencies over the 20,000-Fold Lowering of the Tolerable Daily Intake (TDI) for Bisphenol A (BPA) by the European Food Safety Authority (EFSA).

Vom Saal F, Antoniou M, Belcher S, Bergman A, Bhandari R, Birnbaum L Environ Health Perspect. 2024; 132(4):45001.

PMID: 38592230 PMC: 11003459. DOI: 10.1289/EHP13812.

Important roles of Hif1a in maternal or adult BPA exposure induced pancreatic injuries.

Liu H, Zhou Y, Li Y, Gong Z Sci Rep. 2023; 13(1):11502.

PMID: 37460698 PMC: 10352259. DOI: 10.1038/s41598-023-38614-8.

Effects of perinatal exposure to bisphenol A on induction of prostate cancer in Sprague Dawley rats by MNU and testosterone.

Bosland M, Schlicht M, Acevedo N, Soto A, Prins G Toxicology. 2022; 484:153394.

PMID: 36521576 PMC: 9945469. DOI: 10.1016/j.tox.2022.153394.

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