October 26, 2021

Report by Mott Center researchers named NIEHS Extramural Paper of the Month

The National Institutes of Environmental Health Sciences has selected a study published by Wayne State University School of Medicine researchers as an Extramural Paper of the Month.

The paper, “Paternal preconception phthalate exposure alters sperm methylome and embryonic programming,” published in in the October issue of the journal Environment International by J. Richard Pilsner, Ph.D., professor and Robert J. Sokol, M.D., Endowed Chair of Molecular Obstetrics and Gynecology, and director of Molecular Genetics and Infertility for the C.S. Mott Center for Human Growth and Development; and Stephen Krawetz, Ph.D., the Charlotte B. Failing Professor of Fetal Therapy and Diagnosis, and associate director of the Mott Center, was selected by the NIEHS as a paper of the month for September.

The Extramural Papers of the Month are selected based on their important findings and potential for public health impact.

The researchers reported that male mice exposed to phthalates before conception had DNA methylation changes in sperm, which can be transferred to the next generation as altered gene expression in embryos. DNA methylation occurs when a chemical compound, called a methyl group, attaches to DNA, affecting whether a gene is turned on or off.

They exposed male mice to either a low or high level of di(2-ethylhexyl) phthalate for two sperm production cycles, or 67 days. Following exposure, they mated the mice with unexposed females. They then assessed genome-wide methylation in sperm, embryos and extra-embryonic tissues, which support the developing embryo.

Compared with unexposed controls, paternal preconception DEHP exposure altered methylation in 704 sperm gene regions, 1,716 embryo gene regions, and 3,181 extra-embryonic gene regions. Of these, 29 gene regions overlapped between sperm and embryonic tissues, suggesting methylation changes related to paternal DEHP exposure may be transmitted to the next generation. The researchers also identified changes in gene expression in embryos in both exposure groups compared with controls. Many of the altered genes were related to pathways important in development.

The researchers said their results indicate that preconception is a sensitive window in which phthalate exposure alters sperm methylation and embryo gene expression in ways that may influence offspring health and development.

Others involved in the research and subsequent publication include Oladele Oluwayiose, a doctoral student at the University of Massachusetts Amherst; Chelsea Marcho, Department of Environmental Health Sciences, University of Massachusetts Amherst; Haotian Wu, Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University; Alexander Suvorov, Department of Environmental Health Sciences, University of Massachusetts Amherst; Emily Houle, Department of Environmental Health Sciences, University of Massachusetts Amherst; and Jesse Mager, Department of Veterinary and Animal Sciences, University of Massachusetts Amherst.

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