Endocrine Disruptor BPA Increases Fetal Oxidative Stress

Miriam E Tucker

January 20, 2015

In utero exposure to the endocrine-disrupting chemical bisphenol A (BPA) causes oxidative damage that could predispose the fetus to developing metabolic conditions such as type 2 diabetes and cardiovascular disease later in life, a new study suggests.

The findings were published online January 20, 2015 in Endocrinology by Dr Almundena Veiga-Lopez (University of Michigan, Ann Arbor) and colleagues.

Controversy has surrounded the human health effects of BPA, an endocrine-disrupting industrial chemical that is ubiquitous in the environment and in human bodies. BPA is particularly concentrated in plastic products such as Nalgene containers and food can liners, and has been found in a wide array of paper products, including napkins, toilet paper, food wrappers, newspapers, and even cash receipts.

The chemical has been linked with adverse metabolic-health effects, including type 2 diabetes and heart disease.

The relationship between BPA-induced endocrine disruption and these conditions is thought to occur via oxidative stress, inflammation, and imbalances in free fatty acids, leading to insulin resistance.

But these claims are contentious; a newly issued statement from the European Food Safety Authority (EFSA) this week declared that BPA poses no health risk to consumers of any age, including unborn children, at current levels of exposure.

"Concerning" Information for Pregnant Women?

In this new research, the authors find an association between higher maternal- and cord-blood BPA levels and increased levels of the protein-bound oxidized tyrosine moiety 3-nitrotyrosine Y (NY), a marker of oxidative stress, among a total of 24 pregnant women. They also found similar signs of damage when they gave human-comparable BPA doses to pregnant sheep, rats, and mice.

"Both our animal-testing studies and human-association study indicate risk from BPA exposure during pregnancy," senior author Dr Vasantha Padmanabhan, professor in the departments of pediatrics, obstetrics, and gynecology, molecular and integrative physiology, and environmental health sciences at the University of Michigan, told Medscape Medical News.

"This causal relationship will require intervention and large-scale human studies to further elucidate this issue. The fact that we see a similar association in humans and animals raises concern about potential risk later in life," she noted, adding, "I would find this information concerning and take precautions if I were a pregnant woman."

First BPA Study in Both Humans and Animals

The 24 women all had uncomplicated pregnancies. Blood was taken during their first trimesters (8 to 14 weeks' gestation), and the women were divided into 12 with higher vs 12 with lower BPA levels. Umbilical cord blood samples were taken at birth.

The women with higher BPA levels also had higher blood levels of NY/tyrosine (P < .005), and the cord-blood samples from the newborns of the mothers with greater BPA exposure had higher NY/tyrosine levels compared with the newborns of the lower-exposure group (P < .01).

The higher BPA-exposed group also had increased levels of palmitic acid compared with the lower-exposed group (P = .012), a sign that BPA may disrupt free-fatty-acid balance; the latter is also linked to inflammation and metabolic disruption, Dr Veiga-Lopez and colleagues note.

To strengthen the human findings, the authors treated pregnant rats, mice, and sheep with BPA in quantities that achieved roughly similar blood or tissue levels of BPA to that found in humans and saw a similar relationship between BPA exposure and measures of oxidative stress in their offspring.

Dr Padmanabhan told Medscape Medical News: "This is an extremely controversial field. That's why we included multiple species, because if we find the same association in different species, maybe there's cause for concern."

The Michigan group is now looking at a larger cohort and obtaining consent from the women for future studies.

However, Dr Padmanabhan noted, "It's extremely expensive to measure nitrotyrosines. We need to obtain further funding to proceed."

This study was supported by an American Recovery and Reinvestment Act supplement to a National Institute for Environmental Health Sciences (NIEHS) grant and a grant from the United States Environmental Protection Agency. The authors have reported no relevant financial relationships.

Endocrinology. Published online January 20, 2015. Abstract

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