Counteracting Bisphenol-A (BPA) in Pregnancy: A Rat Study

by | Jul 5, 2017 | 2016, Environmental Health, Indole-3 Carbinol, Pregnancy and Lactation

Written by Marcia J. Egles, MD. Dietary genistein and indole-3 carbinol, when given to pregnant female Sprague-Dawley rats exposed to Bisphenol A, modified the deleterious effect of morphological and gene expression changes induced in mammary glands of the offspring. 

Bisphenol A, or “BPA’, is a chemical widely used for over fifty years in the plastics industry. BPA (and related “replacement” bisphenols) are found in numerous products including food containers, the linings of canned food, PVC pipes, dental sealants, water bottles, baby bottles, cash register tapes and household appliances 1. Numerous studies have reported the presence of BPA in human serum, urine, breast milk, placental tissue, fetal plasma, amniotic fluid and umbilical cord blood 1-4.   Though the health significance of BPA is controversial, BPA has been categorized as an endocrine disruptor with weak estrogenic activity 3.

As exposure to BPA may be unavoidable in a world full of plastics 4(5), the reported study done in rats evaluates two dietary substances which might alter the estrogenic effects of BPA. The two substances are genistein (GEN) and indole-3-carbinol. GEN is the main phytoestrogen found in soy.  Indole-3-carbinol is a natural compound derived from glucobrassicin found in broccoli and related vegetables. Indole-3 carbinol in the diet may bolster the body’s ability to detoxify chemicals by increasing levels of important metabolizing enzymes 5.

In the study, three groups of pregnant female rats were exposed to low dose BPA, higher dose BPA, or no BPA. Each of the two BPA exposed groups were then subdivided to receive GEN or indole-3 carbinol supplements or phytoestrogen-free control rat chow.   The study then focused on the female offspring. When the female pups were 21 days old, their breast tissue was examined for changes in microscopic structure and in gene expression.

The study’s lower dose BPA , at 25 micrograms per kilogram of mother rat body weight per day,( BPA25) is comparatively less than the “safe reference dose” established by the US Environmental Protection Agency for BPA at 50 micrograms per kilogram human body weight per day 5,6.   The higher dose BPA used in this study was 250 micrograms per kilogram body weight.  The respective groups of mother rats, 15 rats per group, received BPA exposures by gastric lavage on day 10 to day 21 of their pregnancies. From gestational day zero to gestational day 21, the dams had free access, according to their group assignment, to the control chow, to GEN supplemented chow (at 250mg GEN per kg of chow) or to indole-3 -carbinol supplemented chow (2000 mg per kg of chow).  Thereafter, including during lactation, the rats all were given the control diet.

In the offspring rats, the study found significant (p less than 0.05) differences in both microscopic breast structure and in gene expression related to BPA exposure and to the receipt of the dietary supplements.   For example, the BPA25 group which received no supplements had a higher number of mammary gland terminal structures, mammary branching and cell proliferation indices than that of the unexposed control group.  The BPA 25 exposed rats who also received either GEN or indole-3 carbinol, had a more normal pattern in their mammary gland structures and indices as compared to the unsupplemented BPA25 group.  Changes in clusters of “up and down” regulated genes associated with breast development were noted in the BPA groups, and were modified by the addition of indole-3-carbinol.

At the higher dose, BPA 250, the changes in mammary gland structure to the female offspring were not observed. This was thought due to a “U-shaped” response curve that can occur in hormone studies 5.

This study done in rats adds to the concern of even “safe” levels of BPA as an environmental risk, particularly in early pregnancy 5. Dietary intakes of vegetables such as broccoli may confer some protection against this risk.

Source: Grassi, Tony F., Glenda N. da Silva, Lucas T. Bidinotto, Bruna F. Rossi, Marília M. Quinalha, Laura Kass, Mónica Muñoz-de-Toro, and Luís F. Barbisan. “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.” Toxicology and applied pharmacology 303 (2016): 101-109.

© 2016 Elsevier Inc. All rights reserved.

Posted July 5, 2017.

References:

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