Environmental Factor

Environmental Factor

Your Online Source for NIEHS News

June 2017

NIEHS research links phthalate exposure and birth defects

An NIEHS research group led by Humphrey Yao, Ph.D., has found that embryos from a particular mouse strain have a higher incidence of birth defects after exposure to phthalates, a group of compounds that soften plastic products and also disrupt endocrine function in animals.

Yao and members of his Reproductive Developmental Biology Group demonstrated that in utero exposure of B6:129S4 mice to di-(2-ethylhexyl)-phthalate (DEHP) resulted in pups born with additional toes (see image). Known as polydactyly, having more than 10 fingers or toes is the most common birth defect in humans.

"This work highlights the importance of animal models in research and will help scientists examine whether the mechanism that causes polydactyly in these mice also occurs in people," Yao said.

Editors of the journal Toxicological Sciences selected an image from the paper as one of four featured on the cover of the issue.

Taking advantage of green fluorescence

Yao studies male reproduction and wanted mice that allowed him to follow the development of sperm and testes. He found what he was looking for in a genetically-modified B6:129S4 mouse, a strain that develops normally like wild-type mice, but is engineered so that the male germ cells fluoresce bright green under a microscope. These germ cells will become sperm in the mature adult.

After identifying the best type of mouse to use, Yao gave pregnant B6:129S4 mice either corn oil or corn oil diluted with varying concentrations of DEHP. Male and female mouse pups born to mothers given DEHP exhibited polydactyly, and the male pups produced abnormal-looking germ cells.

Making the connection

DEHP is the most widely-produced phthalate in the world, according to Yao, so it made sense to use it for his studies. Phthalates appear in a variety of products, such as cosmetics, perfume, plastic wrap, and shampoo.

NIEHS Visiting Fellow Emmi Rotgers, M.D., Ph.D., was involved in the study and said the reproductive issues described in the article were similar to what other scientists have found in animal studies using phthalates. She said although more research is needed to determine if human polydactyly and DEHP-induced polydactyly in B6:129S4 mice are related, the finding has given the group a starting point.

"Phthalates have not been linked to limb malformations before, and it would be important to study which genetic variants make these mice so sensitive to phthalates," Rotgers said.

Citation: Ungewitter E, Rotgers E, Bantukul T, Kawakami Y, Kissling GE, Yao HH. 2017. From the Cover: Teratogenic effects of in utero exposure to di-(2-ethylhexyl)-phthalate (DEHP) in B6:129S4 mice. Toxicol Sci 157(1):8−19.


Yao germ cells

White arrows point to germ cells, stained green, that contain multiple nuclei. The image on the far left is from the control group. Numbers above the other three indicate the dosage of DEHP. (Photo courtesy of Toxicological Sciences, published by Oxford University Press on behalf of the Society of Toxicology, 2017. This work is written by U.S. government employees and is in the public domain in the U.S.)

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