Experts at Wayne State University have identified a mechanism responsible for pregnancy complications due to benzine exposure.

“Hydroquinone impairs trophoblast migration and invasion via AHR-twist-IFITM1 axis,” published in the journal Placenta, was chosen as one of four papers of the month by the National Institute of Environmental Health Sciences.

Gil Mor, M.D., Ph.D., director of the C.S. Mott Center for Human Growth and Development at the Wayne State University School of Medicine, was the senior author. Other members of the C.S Mott Center for Human Growth and Development who contributed to the paper include Wayne State doctoral students Anthony Maxwell, Grace Swanson, Annie Thy Nguyen, Anna Hu, Darby Richards, Yuan You, Laura Stephan and Marcia Manaloto, and Jiahui Ding, Ph.D., assistant professor of Obstetrics and Gynecology at the Wayne State University School of Medicine. Aihua Liao of the Institute of Reproductive Health and Center for Reproductive Medicine at Tongji Medical College at Huazhong University of Science and Technology in Wuhan, China, was also credited.

The National Institute for Environmental Health Sciences of the National Institutes of Health-funded researchers identified a molecular mechanism by which benzene disrupts embryo implantation, thus explaining how air pollution exposure can lead to pregnancy complications.

“When we exposed animal models to benzine, we saw higher rates of abnormal pregnancies and the loss of pregnancies,” Dr. Mor said. “Through this research, we aimed to understand how benzine or its metabolites influence the placenta.”

The team identified the molecular pathway that may create this effect and was able to see the downstream genes that are differentially regulated because of exposure to benzine.
 
“We identified a critical gene responsible for trophoblast migration that is affected by this benzine exposure,” Dr. Mor said. “From a scientific perspective, we now know how benzine is affecting placenta. This opens opportunities for new methods to protect patients exposed to volatile organic compounds (VOCs) during pregnancies. It also gives us the possibility of using these identified pathways as markers to monitor how preterm births happen.”

After attachment of the blastocyst—a cluster of cells forming an early-stage embryo—to the inner lining of the uterus, cells called trophoblasts migrate from the blastocyst to the uterine lining through a process called invasion. Errors in migration or invasion will lead to embryo implantation failure or miscarriage.

The researchers focused on the effect of hydroquinone, a benzene metabolite, on trophoblast function. Trophoblast migration and invasion decreased with increasing concentrations of hydroquinone. The authors said the results suggest benzene exposure affects the pathway critical to regulating trophoblast migration and invasion by reducing the effects of the gene known as Twist1. This insight could inform preventive strategies to reduce exposures.

“Being selected by NIEHS is significant,” Dr. Mor said. “There are many articles and papers about benzine and VOCs, and this honor shows that the organization that is funding our program is paying attention to our work and are seeing how significant it can be.”

Funding for this research was provided by the National Institutes of Health through grant numbers ES030991, OD030484, AI145829, CA022453, HD111146, and ES020957.