BPA activates immune response in mice that passes down through generations

https://www.acs.org/content/acs/en/pressroom/presspacs/2020/acs-presspac-january-15-2019/bpa-activates-immune-response-in-mice-that-passes-down-through-generations.html

http://archive.is/1P96C

Some plastic food and beverage containers still contain bisphenol A (BPA), which can mimic the hormone estrogen. Although experts say that small amounts of BPA detected in foods are unlikely to cause problems, some people worry that constant low-level exposures could have health effects, especially for developing fetuses, infants and children. Now, researchers report in ACS’ Journal of Proteome Research that in mice, BPA activates an immune response that persists for at least three generations.

Epidemiological studies have linked in utero BPA exposure with the onset of childhood asthma. Other studies have shown that treating pregnant mice with the substance induces asthma-like symptoms in the mothers and their pups. To better understand how BPA could trigger allergic asthma, Terumi Midoro-Horiuti, Kangling Zhang and colleagues analyzed the proteins produced by immune cells of BPA-treated pregnant mice, their pups and two generations of mice afterward that had not themselves been exposed to BPA.

Using mass spectrometry, the researchers compared the proteins produced by certain immune cells from BPA-exposed mice and their descendants with those from control mice. In the BPA-exposed mice and subsequent generations, some proteins related to an activated innate immune system –– which plays a key role in antiviral defense and is also related to allergic diseases –– were produced at higher amounts than in control mice. In particular, the BPA-exposed mice and their offspring produced about twice as much of a protein called ZDHHC1, which is also produced at higher levels in response to estrogen. In addition, BPA exposure caused changes in enzymes that modify DNA-binding proteins called histones. That kind of modification can cause heritable changes in gene expression. Therefore, descendants of the original BPA-exposed mice could have inherited changes in DNA expression that cause aberrant immune system activation, even in the absence of BPA, the researchers say.

Full study here:

https://pubs.acs.org/doi/full/10.1021/acs.jproteome.9b00548

http://archive.is/cQsTa

Abstract

Bisphenol A (BPA) is a ubiquitous component in the manufacturing of plastic. It is commonly found in food and beverage containers. Because of its broad exposure and evidence that it may act as an estrogen-like molecule, many have studied its potential effects. For example, epidemiological studies have found an association between in utero BPA exposure and onset of childhood asthma. Our previous work suggested BPA treated mice induced asthma-like symptoms in both mothers and their pups. In order to better understand theconsequences of BPA exposure and potential mechanisms, we used a proteomics approach. Using both CD4+ T cells from an in vivo model of BPA exposure and an in vitro epithelial cell model, we identified activation of both innate and adaptive immune signaling following BPA exposure. Furthermore, our proteomic results from our multigenerational mouse model study implicates aberrant immune activation across several generations. We propose the following; BPA can active an innate viral immune response by upregulating a probable palmitoyltransferase ZDHHC1, and its binding partner stimulator of interferon-gamma (STING). It also has additional histone epigenetic perturbations, suggesting a role for epigenetic inheritance of these immune perturbations.