Research Paper of the Week: Pesticide Methoxychlor Promotes the Epigenetic Transgenerational Inheritance of Adult-Onset Disease through the Female Germline

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by Shea Robison (@EpigeneticsGuy)

Pesticide Methoxychlor Promotes the Epigenetic Transgenerational Inheritance of Adult-Onset Disease through the Female Germline

Policy implications: As this research involves the epigenetic effects of exposure to a very common pesticide and insecticide, there are all sorts of implications for agricultural policies and FDA food safety regulations. These results also address the transgenerational causes of obesity and adult-onset diseases such as kidney disease, so there are significant implications for obesity and health care policies as well. However, given the protocols of the experiments in this study the results are valid primarily as demonstrations of the transgenerational epigenetic effects of methoxychlor, and are only suggestive of the risks of exposure. Still, the fact that methoxychlor is shown to produce these significant and transgenerational epigenetic effects is suggestive of their importance for consideration in the policy domains mentioned.

Summary: As the title clearly states, this paper investigates the potential of methoxychlor to promote the epigenetic transgenerational inheritance of adult-onset disease in both males and females.

Methoxychlor is an insecticide and pesticide that replaced DDT and has been approved for use on crops and livestock since 1946. The effects of methoxychlor have been extensively studied in animals, demonstrating significant estrogenic and reproductive toxicity in both males and females. Methoxychlor has also been found to be carcinogenic. In humans, the toxicity profile of methoxychlor shows “death, systemic (aplastic anemia), cardiovascular (low blood pressure), and neurological (blurred vision, dizziness and paresthesia) effects, and cancer (leukemia).”

In this study, gestating female rats in the F0 generation were given a transient exposure to methoxychlor via intraperitoneal injections during fetal gonadal sex determination. The dose was in the high range of environmental exposure, but no direct toxic effects were anticipated or observed. Diseases of the testis, prostate, kidney, ovary and uterus, as well as tumor development, abnormal puberty onset, obesity and sperm epimutations were evaluated in F1, F3 and F4 generations for both control and methoxychlor lineages. However, because of the dose and the injection method, a realistic risk assessment of environmental exposure to methoxychlor could not be assessed; rather, this was a study of the effects of exposure to methoxychlor on the epigenetic transgenerational inheritance of specific disease phenotypes.

Significant differences from the control lineages in female pubertal abnormalities were observed for the F1 methoxychlor lineages, but not the F3 generations. Significant differences were found for ovary diseases for the F3 methoxychlor, but not the F1. Significant differences in male and female obesity and incidence of multiple disease were also found for F3 methoxychlor generations. For F4 generations, significant differences from the control were found for male and female kidney disease, total disease incidence, and male obesity.

As the authors conclude, “previous studies with vinclozolin or high fat diet showed transmission of increased incidence of disease through the male germline.” What this study adds is that it shows “a transmission of increased incidence of kidney disease in females and males, and obesity in males through the female germline after toxicant exposure to pregnant F0 generation females,” and that “the transmission of transgenerational female obesity may involve a combination of male and female germline transmission.”

Authors: Mohan Manikkam, M. Muksitul Haque, Carlos Guerrero-Bosagna, Eric E. Nilsson, Michael K. Skinner from the Center for Reproductive Biology, School of Biological Sciences, Washington State University, Pullman, Washington, United States of America

Journal: PLoS One

Publication date: July 24, 2014

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