An Oregon Health & Science University researcher has found a way to keep mouse stem cells from differentiating into cells with a specific function in the body. The cells then can be exposed to toxic agents and allowed to mirror normal embryonic development, where they can be monitored for defects. Anne Greenlee, Ph.D., recently presented her research at the developmental toxicology platform session at the Society of Toxicology annual meeting in New Orleans.
"The importance of the research is that developmental anomalies, such as birth defects or fetal death, affect 2 to 3 percent of all babies born in the United States. Approximately 40 percent of these birth defects have unexplained causes. Concern exists that environmental exposures may be playing a significant role. But it has been difficult to evaluate without a model for testing developmental toxicity of more than 80,000 chemicals in commerce - 2,000 are newly introduced annually. Fewer than 5 percent have been tested for reproductive outcomes and even fewer for developmental toxicity," said Greenlee, an associate professor, OHSU School of Nursing, La Grande Campus, and OHSU assistant scientist at the Center for Research on Occupational and Environmental Toxicology. Greenlee conducted the research when she was at the Marshfield Clinic Research Foundation, Marshfield, Wis. The research was published online in Toxicology in Vitro in February after her appointment to OHSU.
Mouse embryonic stem cells offer an inexpensive alternative to whole animal testing for toxins. Research using these cells, especially using Greenlee's technique for stopping differentiation, can help speed research into how certain chemicals affect embryos in the first five to seven days after fertilization.
"Our report provides information on how to maximize their potential for screening purposes, which requires that they be undifferentiated at the start of the toxicity assay. We want the cells to differentiate normally or not in the presence of various toxicants so that we can examine how the chemicals may affect normal pathways of development. Our work attempts to simplify and standardize the culturing of these undifferentiated cells using Matrigel, a gelatin, to coat the plastic surface of the culture dish, rather than using inactivated mouse fibroblasts," Greenlee said.
Greenlee's research involves rural environmental exposures and the risk of infertility, birth defects, prostate cancer and neurologic health. Her previous research, published in Epidemiology, has shown that mixing and applying herbicides or fungicides in the two-year period before trying to conceive increases a woman's risk of infertility.