Transgenerational Epigenetic Inheritance : Pesticides linked to Three Generations of Diseases

Ancestral exposure to pesticides may cause adult onset kidney disease, ovarian disease and obesity in future generations

Implications for Obesity, Fertility, Disease

image of Epigenetic mechanisms
Epigenetic mechanisms – ancestral exposure to pesticides may cause adult onset kidney disease, ovarian disease and obesity in future generations.

Washington State University researchers argues that exposure to the pesticide Methoxychlor – also known as Chemform, Methoxo, Metox or Moxie ; introduced in 1948 and widely used during the 1970s as a safer replacement for DDT – could cause diseases three generations later, in offspring who were never exposed to the chemicals themselves.

Most developed nations have banned the pesticide, which can behave like the hormone estrogen and profoundly affects the reproductive system. Methoxychlor was banned in the U.S. in 2003 but it is still widely used in Mexico and South American countries where the U.S. gets a significant portion of its produce.

Biologist Michael Skinner and his team found that if a rat fetus is exposed to the pesticide during the first trimester of pregnancy, the likelihood of kidney disease, ovary disease and obesity in their progeny was elevated for three generations. Multiple diseases were even more prevalent in the third generation – great-grandchildren – than in the second. This is called transgenerational epigenetic inheritance.


A variety of environmental toxicants have been shown to induce the epigenetic transgenerational inheritance of disease and phenotypic variation. The process involves exposure of a gestating female and the developing fetus to environmental factors that promote permanent alterations in the epigenetic programming of the germline. The molecular aspects of the phenomenon involve epigenetic modifications (epimutations) in the germline (e.g. sperm) that are transmitted to subsequent generations. The current study integrates previously described experimental epigenomic transgenerational data and web-based bioinformatic analyses to identify genomic features associated with these transgenerationally transmitted epimutations. A previously identified genomic feature associated with these epimutations is a low CpG density (<12/100bp). The current observations suggest the transgenerational differential DNA methylation regions (DMR) in sperm contain unique consensus DNA sequence motifs, zinc finger motifs and G-quadruplex sequences. Interaction of molecular factors with these sequences could alter chromatin structure and accessibility of proteins with DNA methyltransferases to alter de novo DNA methylation patterns. G-quadruplex regions can promote the opening of the chromatin that may influence the action of DNA methyltransferases, or factors interacting with them, for the establishment of epigenetic marks. Zinc finger binding factors can also promote this chromatin remodeling and influence the expression of non-coding RNA. The current study identified genomic features associated with sperm epimutations that may explain in part how these sites become susceptible for transgenerational programming.

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