Two stories from Washington University the first not directly related to autism per se but highlights epigentic changes over generations in mice exposed to dioxin and the second regarding BPA suspected of having some association with autism (http://www.ncbi.nlm.nih.gov/pubmed/22458970).
Dioxin causes disease, reproductive problems across generations
Wednesday, Sept. 26, 2012
By Eric Sorensen, WSU science writer
PULLMAN, Wash. – Since the 1960s, when the defoliant Agent Orange was widely used in Vietnam, military, industry and environmental groups have debated the toxicity of one of its ingredients, the chemical dioxin, and how it should be regulated.
But even if all the dioxin were eliminated from the planet, Washington State University researchers say its legacy would live on in the way it turns genes on and off in the descendants of people exposed over the past half century.
Writing in the journal PLoS ONE, biologist Michael Skinner and members of his lab say dioxin administered to pregnant rats resulted in a variety of reproductive problems and disease in subsequent generations. The first generation of rats had prostate disease, polycystic ovarian disease and fewer ovarian follicles, the structures that contain eggs. To the surprise of Skinner and his colleagues, the third generation had even more dramatic incidences of ovarian disease and, in males, kidney disease.
“Therefore, it is not just the individuals exposed, but potentially the great-grandchildren that may experience increased adult-onset disease susceptibility,” says Skinner.
Skinner is a professor of reproductive biology and environmental epigenetics – the process in which environmental factors affect how genes are turned on and off in the offspring of an exposed animal, even though its DNA sequences remain unchanged. In this year alone, Skinner and colleagues have published studies finding epigenetic diseases promoted by jet fuel and other hydrocarbon mixtures, plastics, pesticides and fungicides, as well as dioxin.
The field of epigenetics opens new ground in the study of how diseases and reproductive problems develop. While toxicologists generally focus on animals exposed to a compound, work in Skinner’s lab further demonstrates that diseases can also stem from older, ancestral exposures that are then mediated through epigenetic changes in sperm.
This latest study was funded by the U.S. Department of Defense, the National Institutes of Health and the National Institute of Environmental Health Sciences. Skinner designed the study; the research was done by Assistant Research Professor Mohan Manikkam, Research Technician Rebecca Tracey and Post-doctoral Researcher Carlos Guerrero-Bosagna.
The study, “Dioxin (TCDD) Induces Epigenetic Transgenerational Inheritance of Adult Onset Disease and Sperm Epimutations,” is available at http://dx.plos.org/10.1371/journal.pone.0046249.
Primate study adds to evidence of BPA harm to humans
Monday, Sept. 24, 2012
By Eric Sorensen, WSU science writer
PULLMAN, Wash.—A Washington State University researcher has found new evidence that the plastic additive BPA can disrupt women’s reproductive systems, causing chromosome damage, miscarriages and birth defects.
Writing in the journal, Proceedings of the National Academy of Sciences, WSU geneticist Patricia Hunt and colleagues at WSU and the University of California, Davis, report seeing reproductive abnormalities in rhesus monkeys with BPA levels similar to those of humans. By using an animal with the most human-like reproductive system, the research bolsters earlier work by Hunt and others documenting widespread reproductive effects in rodents.
“The concern is exposure to this chemical that we’re all exposed to could increase the risk of miscarriages and the risk of babies born with birth defects like Down Syndrome,” says Hunt. “The really stunning thing about the effect is we’re dosing grandma, it’s crossing the placenta and hitting her developing fetus, and if that fetus is a female, it’s changing the likelihood that that female is going to ovulate normal eggs. It’s a three-for-one hit.”
The research also adds to the number of organs affected by BPA, or bisphenol A, which is found in plastic bottles, the linings of aluminum cans and heat-activated cash register receipts. This May, Hunt was part of another paper in PNAS reporting that the additive altered mammary development in the primate, increasing the risk of cancer.
Hunt’s colleagues at UC, Davis exposed different groups of gestating monkeys to single daily doses of BPA and low-level continuous doses and looked at how they affected the reproductive systems of female fetuses. She saw that in the earliest stage of the adult’s egg development, the egg cell failed to divide properly. Earlier mouse studies showed similar disturbances translated into genetic defects in the mature egg.
A fertilized egg with the wrong number of chromosomes will almost always fail to come to term, leading to a spontaneous abortion or progeny with birth defects.
In monkeys exposed continuously, Hunt saw further complications in the third trimester as fetal eggs were not packaged appropriately in follicles, structures in which they develop. Eggs need to be packaged properly to grow, develop and mature.
“That’s not good,” says Hunt, “because it looks to us like you’re just throwing away a huge number of the eggs that a female would have. It raises concerns about whether or not she’s going to have a really short reproductive lifespan.”
Funding for the study included grants from National Institute of Environmental Health Sciences and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Both are part of the National Institutes of Health.
Does perinatal exposure to endocrine disruptors induce autism spectrum and attention deficit hyperactivity disorders? Review.
Department of Health and Life Sciences, VU University, Amsterdam, The Netherlands.
To provide an overview of studies on perinatal exposure in humans to endocrine disrupting chemicals (EDCs) in relation to autism spectrum (ASD) and attention deficit hyperactivity (ADHD) disorders.
A review of the literature (PubMed) was performed. Exposure-related keywords, including various chemicals, were matched with keywords describing outcome. Animal studies as well as publications not written in English were excluded. In total, 834 titles were retrieved. The final selection included 21 publications.
Positive associations were found for ASD in relation to exposure to all chemicals investigated, which included hazardous air pollutants, pesticides and bisphenol A (BPA).
Increased risks of ADHD or positive associations were found for exposure to polychlorinated biphenyls (PCBs), dialkyl phosphate (DAP) and chlorpyrifos. BPA, polybrominated diphenylethers (PBDEs) and low molecular weight (LMW) phthalates were positively associated with externalizing behaviour. Five of 17 studies did not find any association between exposure and ADHD.
Perinatal exposure to EDCs appears to be associated with the occurrence of ASD as well as ADHD. Disruption of thyroid hormone function and gamma-aminobutyric acid (GABA)ergic mechanisms may offer an explanation for the observed relations; though, conclusive evidence in humans is limited.