How your great grandmother’s chemical exposures may affect you.

Jul 16, 2012

Nilsson, E, G Larsen, M Manikkam, C Guerrero-Bosagna, MI Savenkova and MK Skinner. 2012. Environmentally induced epigenetic transgenerational inheritance of ovarian disease. PLoS ONE http://dx.doi.org/10.1371/journal.pone.0036129.

Synopsis by Glenys Webster

Ovarian diseases that persist across three generations develop in rats exposed to common environmental chemicals at a key time before birth. The symptoms resemble two types of ovarian problems common in women. The results suggest that environmental exposures may play a role in these diseases, including DNA changes that can be passed to future generations.

Female rats exposed to chemicals while growing in the womb can develop ovarian problems similar to common ovarian diseases in women, suggests a research study in the online journal PLoS ONE. The chemicals can reprogram how DNA is expressed in the developing fetus' eggs, setting the stage for ovarian disease later in their life.

Importantly, these epigenetic changes are then passed on to future generations. The implications of the research are profound. The results demonstrate that chemical exposures in just one generation can affect the risk of ovarian disease in at least the next three generations – even though the younger animals were not exposed to the chemicals.

Five chemical treatments were tested and all had effects. They included a fungicide; two phthalates; and plastic, pesticide and hydrocarbon mixtures.

It is not known if similar processes occur in women. But if they do, it could mean that a woman’s exposures during pregnancy may affect the risk of ovarian disease in her daughters, granddaughters and even great-granddaughters.

Other diseases, including allergies and asthma; liver, gastric, prostate and colorectal cancer; and psychiatric disorders are thought to have an epigenetic component. This is the first time that epigenetic changes have been shown in association with ovarian disease.

Up to 18 percent of women suffer from ovarian disease, including Polycystic Ovarian Syndrome (PCOS) and Premature Ovarian Insufficiency (POI). Women with PCOS have fluid-filled sacs (or cysts) on their ovaries – sometimes looking like pearls on a necklace – which can cause pain and infertility. Irregular periods and excess facial hair are other common symptoms of PCOS. Women with POI have abnormal hormone levels and fewer available eggs, signaling poorly functioning ovaries. Both conditions can reduce a woman’s chance of becoming pregnant.

Researchers at Washington State University exposed pregnant rats to one of five different chemicals alone or in mixtures during a critical time of pregnancy when their daughter pups' eggs were developing. The pups were then mated with males from the same treatment group, and the resulting pups were bred yet again. Only the original generation of pregnant rats had been exposed to the chemicals. The adult daughters and great granddaughters of the dosed animals (called the F1 and F3 generations) were examined for ovarian disease.

The U.S. Department of Defense – which partially funded the study – helped select the chemical treatments based on potential exposures in military personnel. The five treatments included vinclozolin, a fungicide that is used in the wine industry; a pesticide mixture including permethrin and DEET; a plastic mixture including bisphenol A (BPA) and two widely used phthalates (DEHP and DBP); the industrial byproduct dioxin; and a hydrocarbon mixture called jet fuel, which is used to control dust on road surfaces.

In all exposure groups, both the daughter (F1) and great-granddaughter (F3) mice had fewer egg follicles in their ovaries compared to controls, indicating a reduced pool of available eggs. Both generations – but particularly the F3 animals – also had an increased number of ovarian cysts compared to controls. These findings are characteristic of POI and PCOS in humans.

Besides the changes to the ovaries themselves, the researchers also found epigenetic changes in the descendents of rats exposed to vinclozolin during pregnancy. In ovarian cells, 523 genes were expressed differently in the great granddaughters of vinclozolin-exposed rats compared to unexposed controls. Thirty of these genes are related to ovarian disease and five are directly related to PCOS.

These findings demonstrate that a commonly used fungicide can induce changes in genes associated with ovarian disease three generations after the initial exposure.

This proof-of-concept study used higher doses of chemicals than what people would typically encounter. Future work is needed to investigate whether lower, more environmentally relevant chemical levels also affect ovarian disease across generations of the rodents.

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