BPA exposure in the womb alters key mammary gland proteins at puberty.

May 13, 2010

Betancourt, AM, JA Mobley, J Russo and CA Lamartiniere. 2010. Proteomic analysis in mammary glands of rat offspring exposed in utero to bisphenol A. Journal of Proteomics http://dx.doi.org/10.1016/j.jprot.2010.02.020.

Synopsis by Laura Vandenberg

A study with rats finds that exposure to low doses of BPA during development changes some of the proteins expressed by the mammary gland - including those that control cell proliferation and death - before and during puberty in ways consistent with cancer formation.

Prenatal exposure to BPA changes the way certain proteins that regulate mammary cell division and growth function at another crucial time of development: during puberty, a period where the mammary gland is undergoing many developmental changes. The series of protein changes align with what is known about how cancer forms.

This is the first time the chemical has been shown to influence key cell development through the proteins that guide these later-life processes. The results may shed light on if and how BPA contributes to breast cells turning cancerous.

Previous studies show that exposure to low levels of BPA in the womb can affect the mouse and rat mammary gland. These prenatal exposures can induce cancerous lesions in the gland. Several other studies also indicate that BPA affects tissue architecture, which depends on cell division, growth and death.

The study also highlights how short exposures during critical times of development can cause seemingly subtle, protein-based changes that can lead to bigger, long-term health consequences, such as cancer. The particular proteins followed in this study are key to maintain cell cycles; repair DNA; prevent cell death; and spur cells to change types, sleep or move to another location.

Thus, this chemical does not need to cause mutations in the DNA itself to have serious effects. Instead, BPA appears to influence how often any given gene is "read" in the cell, which leads to changes in how much of a protein is made. In this way, BPA induces epigenetic changes, where profound effects can occur because important genes are turned on or off at inappropriate times.

BPA is a chemical found in many consumer products, including polycarbonate plastics, epoxy resins that line food and drink cans, dental sealants and some thermal copy papers. Exposure to low levels is constant and ubiquitous; adults and fetuses are exposed from a variety of these sources.

Because BPA acts like an estrogen in the body, there is concern that it can affect the normal development of estrogen-sensitive organs, such as the milk-producing mammary gland. Breast cancers causes the most cancer-related deaths in women worldwide.

In the study, the mammary glands of rats exposed to BPA before birth through their mothers were examined after birth to identify which proteins were affected. The mother rats were tube-fed one of two doses of BPA – either 25 or 250 micrograms/kilogram/day – from day 10 until day 21 of gestation. The lower dose is below the level considered “safe” by the U.S. Environmental Protection Agency. At age 21 and 50 days – the period of development when the mammary gland is sensitive to carcinogens – the mammary glands from exposed and unexposed female offspring were compared.

Many more general health measures did not change. The exposure levels were not toxic; body weight and reproductive organ development were not altered; and hormone levels did not change.

What did change were the on and off signals of some 21 proteins at both the 21 and 50 day windows. Many were turned on; others were turned off. Some of these proteins are known to be responsible for controlling cell proliferation, which may indicate a direct link between BPA exposure and cancer. Several are even expressed in human cancers. Other proteins affected by BPA are important in establishing communication between cells in the mammary gland and cell death.