Prenatal bisphenol A exposure induces preneoplastic lesions in the mammary gland in Wistar rats.
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.
Durando
Milena
M
Laboratorio de Endocrinologia y Tumores Hormonodependientes, School of Biochemistry and Biological Sciences, Universidad Nacional del Litoral, Santa Fe, Argentina.
Kass
Laura
L
Piva
Julio
J
Sonnenschein
Carlos
C
Soto
Ana M
AM
Luque
Enrique H
EH
Muñoz-de-Toro
Mónica
M
D000477:Alkylating Agents; D000818:Animals; D001559:Benzhydryl Compounds; D001943:Breast Neoplasms / Q000139:chemically induced / Q000473:pathology; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005260:Female; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000254:growth & development / Q000473:pathology; D008770:Methylnitrosourea; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D012741:Sexual Maturation / Q000187:drug effects; D000098826:Bisphenol A Compounds
D000477:Alkylating Agents; D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal; D008770:Methylnitrosourea; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds