Michael Skinner, Ph.D.
Washington State University
NIEHS Grant R01ES012974
A study supported in part by the NIEHS showed that ancestral exposure to the pesticide methoxychlor may lead to greater susceptibility of future generations to adult onset kidney disease, ovarian disease, and obesity. The research indicates that exposure to methoxychlor, which was widely used in the 1970s as a DDT replacement, can promote epigenetic transgenerational inheritance of disease in the female germline.
Methoxychlor was banned in the U.S. in 2003 because of its toxicity and ability to disrupt the endocrine system, but it is still used in many countries. The researchers were interested in investigating whether this pesticide could promote epigenetic transgenerational inheritance, which is a non-genetic form of inheritance in which epigenetic changes are passed across generations without any direct environmental exposure. They observed that pregnant rats exposed to methoxychlor at a range of levels typical of high environmental exposures showed increases in the incidence of kidney disease, ovary disease, and obesity in offspring spanning three generations. Analysis of the third generation sperm epigenome of the methoxychlor lineage males identified differentially DNA methylated regions termed epimutations. Additional experiments showed that transgenerational disease transmission occurred primarily through the maternal germline.
These new findings add to the research team’s earlier studies showing a variety of epigenetic effects for contaminants including DDT, plastics, pesticides, fungicides, dioxins, hydrocarbons, and bisphenol A.
Citation: Manikkam M, Haque MM, Guerrero-Bosagna C, Nilsson EE, Skinner MK. 2014. Pesticide methoxychlor promotes the epigenetic transgenerational inheritance of adult-onset disease through the female germline. PLoS One 9(7):e102091.