A Hidden Medical Legacy: How Habits Influence Health Across Generations

By Amita Bansal, Ph.D.   @amita_bansal

Every day we are exposed to a compound, Bisphenol A (BPA), a manmade chemical commonly used in many types of consumable goods, from the linings of canned and packaged foods to plastic bottles, and even baby pacifiers, paper receipts and eyeglasses. Our exposure to BPA is ubiquitous; we are exposed through what we eat, drink and touch. BPA can even be found on unwashed hands. Detectable amounts of BPA are found in urine of >90% of the United States population (1). Recently, BPA has captured even more attention because of its association with increased risk of diabetes and obesity in humans and animals. BPA is believed to disrupt the normal hormonal activity in the body, and is therefore scientifically categorized as an endocrine disrupting chemical.

Kapa65

Penn researchers use a mouse model to study how Bisphenol A (BPA) exposure affects multiple generations. (Image Credit: Kapa65 Pixabay, Public Domain)

In our laboratory, using a mouse model, we have demonstrated that offspring (first generation progeny, or the mouse’s “children,” and second generation progeny, or the mouse’s “grandchildren”) of mothers who were exposed to BPA (lower BPA group: 10 micrograms per kilogram of body weight per day, and upper BPA group: 10 milligrams per kilogram of body weight per day) in their food throughout pregnancy and the nursing period were significantly fatter and had reduced ability to metabolize glucose compared to first and second generation progeny of mothers who were not exposed to BPA (control group) (1). Male offspring were mostly affected and female offspring unaffected (1). Most frightening, the BPA doses used in this study were within the current safe human exposure levels. How the effects of BPA are transmitted from one generation to the next remains unknown. One possible effect of BPA is its effect on glucose metabolism.

We know that in order to metabolize glucose, beta cells of the pancreas produce a hormone called insulin. Insulin acts on target tissues such as liver, muscle, and fat, where glucose is processed. The body fails to metabolize glucose when either beta cells do not produce enough insulin (insulin secretory failure), or insulin fails to affect the target tissue (insulin resistance). To see which of these mechanisms might be at work, we performed physiological tests in our animals. We found that first and second generation progeny of mothers exposed to lower doses of BPA, especially males, had reduced insulin secretion, while those from mothers exposed to high doses of BPA were insulin resistant compared to mice that were never exposed to BPA. In BPA-exposed male animals we also observed defects in beta-cell mitochondrial function. Healthy mitochondria are essential to meet the energy demands for insulin secretion. We wanted to know what mechanisms caused these inter-generational changes.

BPA products photo_19 Nov 2015

BPA is found in many everyday items. (Image Credit: Public Domain c/o Amita Bansal.)

To see if BPA was affecting how genes are turned on and off, we screened expression levels of genes that play an important role in insulin secretion in pancreas and insulin action in liver. Using a high throughput next-generation whole transcriptome sequencing technique, RNA Seq, we found that both lower and upper doses of BPA exposure in mothers alter expression of several pancreatic genes in male offspring. We have also used a real-time measure of gene expression levels, called qPCR, to measure gene expression changes in pancreas and liver. Our qPCR findings indicate that expression levels of several pancreatic and liver genes are altered in children and grandchildren of lower and upper dose BPA exposed mothers. Currently, we are investigating whether epigenetic alterations, i.e. changes where expression of a gene is altered without changing the DNA sequence, are involved in the transmission of the observed gene expression changes from one generation to the next.

Our findings using a mouse model suggest that exposure to BPA in the womb and throughout nursing has deleterious effects on the metabolic health of the first and second generation progeny, especially in male mice. Although we don’t know if BPA affects humans in the same way it affects mice, we suggest that, to be safe, people should make informed decisions while shopping for groceries, adapt a healthy lifestyle and choose fresh fruits and vegetables as opposed to canned and packaged foods. Importantly, policy makers should also consider strictly regulating overall use of BPA in manufacturing products, which might otherwise have severe public health consequences.

 

REFERENCES

  1. Susiarjo M et al. Bisphenol a exposure disrupts metabolic health across multiple generations in the mouse. Endocrinology. 2015;156(6):2049-2058. doi: 2010.1210/en.2014-2027. Epub 2015 Mar 2025.
  2. Calafat AM, Ye X, Wong LY, Reidy JA, Needham LL. Exposure of the U.S. population to bisphenol A and 4-tertiary-octylphenol: 2003-2004. Environ Health Perspect. 2008;116(1):39-44. doi: 10.1289/ehp.10753.
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