Fetal exposure to PVC plastic chemical linked to obesity in offspring: Over multiple generations

Contact: Tom Vasich tmvasich@uci.edu 949-824-6455 University of California – Irvine

UCI study identifies transgenerational effects of obesogen compound tributyltin

Irvine, Calif. — Exposing pregnant mice to low doses of the chemical tributyltin – which is used in marine hull paint and PVC plastic – can lead to obesity for multiple generations without subsequent exposure, a UC Irvine study has found.

After exposing pregnant mice to TBT in concentrations similar to those found in the environment, researchers saw increased body fat, liver fat and fat-specific gene expression in their “children,” “grandchildren” and “great-grandchildren” – none of which had been exposed to the chemical.

These findings suggest that early-life exposure to endocrine-disrupting compounds such as TBT can have permanent effects of fat accumulation without further exposure, said study leader Bruce Blumberg, UC Irvine professor of pharmaceutical sciences and developmental & cell biology. These effects appear to be inherited without DNA mutations occurring.

The study appears online Jan. 15 in Environmental Health Perspectives, a publication of the National Institute for Environmental Health Sciences.

Human exposure to TBT can occur through PVC plastic particles in dust and via leaching of the chemical and other related organotin compounds from PVC pipes and containers.

Significant levels of TBT have been reported in house dust – which is particularly relevant for young children who may spend significant time on floors and carpets. Some people are exposed by ingesting seafood contaminated with TBT, which has been used in marine hull paint and is pervasive in the environment.

Blumberg categorizes TBT as an obesogen, a class of chemicals that promote obesity by increasing the number of fat cells or the storage of fat in existing cells. He and his colleagues first identified the role of obesogens in a 2006 publication and showed in 2010 that TBT acts in part by modifying the fate of mesenchymal stem cells during development, predisposing them to become fat cells.

###

UC Irvine developmental & cell biology postdoctoral fellow Raquel Chamorro Garcia undergraduate student Margaret Sahu and former students Rachelle Abbey, Jhyme Laude and Nhieu Pham contributed to the current study, which was supported by the National Institutes of Health (grants ES-015849 and ES-015849-01S1).

About the University of California, Irvine: Founded in 1965, UC Irvine is a top-ranked university dedicated to research, scholarship and community service. Led by Chancellor Michael Drake since 2005, UC Irvine is among the most dynamic campuses in the University of California system, with more than 28,000 undergraduate and graduate students, 1,100 faculty and 9,400 staff. Orange County’s second-largest employer, UC Irvine contributes an annual economic impact of $4.3 billion. For more UC Irvine news, visit news.uci.edu.

News Radio: UC Irvine maintains on campus an ISDN line for conducting interviews with its faculty and experts. Use of this line is available for a fee to radio news programs/stations that wish to interview UC Irvine faculty and experts. Use of the ISDN line is subject to availability and approval by the university.

Contact:

Tom Vasich 949-824-6455 tmvasich@uci.edu

UCI maintains an online directory of faculty available as experts to the media. To access, visit www.today.uci.edu/experts.

Persistent pollutant may promote obesity: Tributyltin shown to affect gene activity at extremely low concentrations

2008 study posted for filing

Contact: Jennifer Williams
jwilliams@aibs.org
202-628-1500 x209
American Institute of Biological Sciences

Persistent pollutant may promote obesity

Compound shown to affect gene activity at extremely low concentrations

Tributyltin, a ubiquitous pollutant that has a potent effect on gene activity, could be promoting obesity, according to an article in the December issue of BioScience. The chemical is used in antifouling paints for boats, as a wood and textile preservative, and as a pesticide on high-value food crops, among many other applications.

Tributyltin affects sensitive receptors in the cells of animals, from water fleas to humans, at very low concentrations—a thousand times lower than pollutants that are known to interfere with sexual development of wildlife species. Tributyltin and its relatives are highly toxic to mollusks, causing female snails to develop male sexual characteristics, and it bioaccumulates in fish and shellfish.

The harmful effects of the chemical on the liver and the nervous and immune systems in mammals are well known, but its powerful effects on the cellular components known as retinoid X receptors (RXRs) in a range of species are a recent discovery. When activated, RXRs can migrate into the nuclei of cells and switch on genes that cause the growth of fat storage cells and regulate whole body metabolism; compounds that affect a related receptor often associated with RXRs are now used to treat diabetes. RXRs are normally activated by signaling molecules found throughout the body.

The BioScience article, by Taisen Iguchi and Yoshinao Katsu, of the Graduate University for Advanced Studies in Japan, describes how RXRs and related receptors are also strongly activated by tributyltin and similar chemicals. Tributyltin impairs reproduction in water fleas through its effects on a receptor similar to the RXR. In addition, tributyltin causes the growth of excess fatty tissue in newborn mice exposed to it in utero. The effects of tributytin on RXR-like nuclear receptors might therefore be widespread throughout the animal kingdom.

The rise in obesity in humans over the past 40 years parallels the increased use of industrial chemicals over the same period. Iguchi and Katsu maintain that it is “plausible and provocative” to associate the obesity epidemic to chemical triggers present in the modern environment. Several other ubiquitous pollutants with strong biological effects, including environmental estrogens such as bisphenol A and nonylphenol, have been shown to stimulate the growth of fat storage cells in mice. The role that tributyltin and similar persistent pollutants may play in the obesity epidemic is now under scrutiny.

 

###

 

After noon EST on 1 December and for the remainder of the month, the full text of the article will be available for free download through the copy of this Press Release available at http://www.aibs.org/bioscience-press-releases/.

BioScience, published 11 times per year, is the journal of the American Institute of Biological Sciences (AIBS). BioScience publishes commentary and peer-reviewed articles covering a wide range of biological fields, with a focus on “Organisms from Molecules to the Environment.” The journal has been published since 1964. AIBS is an umbrella organization for professional scientific societies and organizations that are involved with biology. It represents some 200 member societies and organizations with a combined membership of about 250,000.