Damage from toxins can pass to offspring
By Elizabeth Weise, USA TODAY
Scientists have shown for the first time that exposure to environmental toxins can cause permanent genetic changes that are passed down through generations.
The research on rats by a team of scientists led by Michael Skinner at Washington State University in Pullman, Wash., may hold the key to the mystery of male infertility, which some researchers say has been increasing for unknown reasons for 20 years. According to a report in today's edition of the journal Science, Skinner's team was working with two commonly used chemicals, an insecticide called methoxychlor and a fungicide called vinclozolin. Both are known to cause infertility in the male offspring of pregnant animals.
The scientists were looking at the rats and their offspring. But when the offspring had offspring, the researchers were shocked by what they found in this second generation. And they were even more surprised by subsequent generations of the lab rats. "Lo and behold they had the same" infertility problems, says Skinner, director of the university's Center for Reproductive Biology. Not only the grandsons but also the great-grandsons and great-great grandsons of the exposed mother were similarly affected. The scientists had discovered a mechanism that permanently changed the reproductive cells.
"That (the changes are) carried down through the generations is what's new and novel here," says Paul Turek, a male infertility specialist at the University of California at San Francisco. "Everyone agrees that exposure of the fetus at a certain critical time can cause malformed organs and birth defects. But no one ever imagined this might persist at some level for three more generations."
Skinner notes that rat studies cannot necessarily be applied to humans, but he said the findings warrant a close look at the potential health hazards of environmental chemicals. The exposure appears to produce what's called an epigenetic effect, in which a chemical modification of the DNA in the animal's reproductive cells causes an alteration with potentially disastrous results — in this case, infertility. Epigenetic effects are generally erased with each new generation when the cells that form the sperm or eggs are created in the embryo. But in this case, the affected genes maintained the alteration and escaped the reprogramming process.
Skinner cautions that the doses used in his research are higher than those normally found in the environment. He plans to begin testing at lower doses to see whether the same changes appear. Human exposure to methoxychlor, which is being phased out in the USA, and vinclozolin is mostly restricted to agricultural workers, though there's not much data to go on, Skinner says. He expects that other researchers will now begin looking for similar effects in people.
But "to the extent that it's been studied, the epigenetic effects seen in rodents are similar to those seen in humans," says John McCarrey, an expert on epigenetics at the University of Texas at San Antonio. The findings may one day facilitate new diagnostic approaches and therapies, Skinner says. For example, doctors would be on the lookout much earlier for certain diseases if they knew that their patients' ancestors had been exposed to certain toxins, he says.
Environmental Toxicants Like Lead, Mercury Target Stem Cells 07 Feb 2007
Low levels of toxic substances cause critical stem cells in the central nervous system to prematurely shut down. That is the conclusion of a study published in the on-line journal PLoS Biology. This research, which is the first to identify a common molecular trigger for the effects of toxicant exposure, may give scientists new insights into damage caused by toxicant exposure and new methods of evaluating the safety of chemicals.
While scientists have long understood that certain chemicals like lead and mercury have adverse effects on the body, the precise molecular mechanism by which many of these substances cause harm remain uncertain. This makes it more difficult to concretely link individual toxic substances with specific diseases or determine - with greater confidence - whether or not a chemical is toxic. However, recent advances in molecular biology, genetics, and stem cell biology have provided scientists a new window onto the impact of toxic substances on the cellular and molecular level.
"Establishing the general principles underlying the effects of toxicant exposure on the body is one of the central challenges of toxicology research," said University of Rochester biomedical geneticist Mark Noble, Ph.D., senior author of the study. "We have discovered a previously unrecognized regulatory pathway on which chemically diverse toxicants converge and disrupt normal cell function."
Noble and his colleagues exposed a specific population of brain cells to low levels of lead, mercury, and paraquat, one of the most widely used herbicides in the world. These cells, called glial progenitors, are advanced-stage stem cells that are critical to the growth, development, and normal function of the central nervous system. The activity of cells is regulated by molecular pathways - or controlled chemical reactions - normally set off when substances bind to receptors on the cell's surface. Noble and his colleagues found that these compounds turned off specific sets of receptors and set into motion a molecular chain reaction that causes the cells to shut down and stop dividing.
"These toxicants are activating a normal cellular regulatory pathway, they are just activating it inappropriately," said Noble. "If this disruption occurs during critical developmental periods, like fetal growth or early childhood, it can have a significant impact. Development is a cumulative process, and the effects of even small changes in progenitor cell division and differentiation over multiple generations could have a substantial effect on an organism."
This study is an example of the ability of stem cell research to shed new light on many diseases and health problems that have heretofore been poorly understood by the medical community. Noble and his colleagues are pioneers in the field and have been involved in the discovery of several of the progenitor cells that are involved in building the central nervous system. The growing knowledge of the precise timing and role of these cells has enabled scientists to explore the molecular origin of these diseases, and the Rochester team's findings are part of a growing number of discoveries that indicate that certain developmental syndromes may be the result of disruption in stem cell function.
There are tens of thousands of synthetic industrial chemicals, pesticides, metals, and other substances for which toxicological information is limited or nonexistent. By identifying a molecular target that is shared by toxic substances, all with very different chemical compositions, this discovery may give scientists a method to rapidly evaluate compounds to determine whether or not they pose a potential health threat.
"One of the obstacles in the analysis of new chemicals is the difficulty in developing a system that is sensitive enough and can make predictions that are true for both individual cells and the entire organism," said Noble. "This novel pathway gives as a way to analyze a diverse array of chemicals at levels in which they would be encountered in the environment. Furthermore, by identifying a specific molecular pathway that is activated by toxic exposure, we can now begin to look at specific ways to protect cells from this disruption of signaling."
Funding for the research came from National Institute of Environmental Health Sciences. Other investigators participating in the study were lead author Zaibo Li, M.D., Ph.D., Tiefei Dong, Ph.D., and Chris Proschel, Ph.D., all with the University of Rochester Medical Center.
Contact: Mark Michaud
University of Rochester Medical Center
Article URL: http://www.medicalnewstoday.com/medicalnews.php?newsid=62421
Subject: Government Study Confirms Genetically Modified Crops Threaten Human Fertility and Health Safety
Media Contact: NJ Jaeger
Austrian Government Study Confirms Genetically Modified (GM) Crops
Threaten Human Fertility and Health Safety
Advocates Call for Immediate Ban of All GM Foods and GM Crops
IMMEDIATE RELEASE (November 13, 2008)
(Los Angeles, CA.) - A long-term feeding study commissioned by the Austrian Agency for Health and Food Safety, managed by the Austrian Federal Ministry of Health, Family and Youth, and carried out by Veterinary University Vienna, confirms genetically modified (GM) corn seriously affects reproductive health in mice. Non-GMO advocates, who have warned about this infertility link along with other health risks, now seek an immediate ban of all GM foods and GM crops to protect the health of humankind and the fertility of women around the world.
Feeding mice with genetically modified corn developed by the US-based Monsanto Corporation led to lower fertility and body weight, according to the study conducted by the University of Veterinary Medicine in Vienna. Lead author of the study Professor Zentek said, there was a direct link between the decrease in fertility and the GM diet, and that mice fed with non-GE corn reproduced more efficiently.
In the study, Austrian scientists performed several long-term feeding trials over 20 weeks with laboratory mice fed a diet containing 33% of a GM variety (NK 603 x MON 810), or a closely related non-GE variety used in many countries. Statistically significant litter size and pup weight decreases were found in the third and fourth litters in the GM-fed mice, compared to the control group.
The corn is genetically modified with genes that produce a pesticidal toxin, as well as genes that allow it to survive applications of Monsanto's herbicide Roundup.
A book by author Jeffrey M. Smith, Genetic Roulette, distributed to members of congress last year, documents 65 serious health risks of GM products, including similar fertility problems with GM soy and GM corn: Offspring of rats fed GM soy showed a five-fold increase in mortality, lower birth weights, and the inability to reproduce. Male mice fed GM soy had damaged young sperm cells. The embryo offspring of GM soy-fed mice had altered DNA functioning. Several US farmers reported sterility or fertility problems among pigs and cows fed on GM corn varieties. Additionally, over the last two months, investigators in India have documented fertility problems, abortions, premature births, and other serious health issues, including deaths, among buffaloes fed GM cottonseed products.
The principle GM crops are soy, corn, cottonseed and canola. GM sugar from sugar beets will also be introduced before year's end.
Mr. Smith, who is also the Executive Director of the Institute for Responsible Technology says, "GM foods are likely responsible for several negative health trends in the US. The government must impose an immediate ban on these dangerous crops." He says, "Consumers don't need to wait for governmental action. They can download a free Non-GMO Shopping Guide at www.HealthierEating.org."
Monsanto press offices in the UK and USA were unable to provide a comment on the findings for journalists yesterday.
The Institute for Responsible Technology's Campaign for Healthier Eating in America mobilizes citizens, organizations, businesses, and the media, to achieve the tipping point of consumer rejection of genetically modified foods.
The Institute educates people about the documented health risks of GMOs and provides them with healthier non-GMO product choices.
The Institute also informs policy makers and the public around the world about the impacts of GMOs on health, environment, the economy, and agriculture, and the problems associated with current research, regulation, corporate practices, and reporting.
Institute For Responsible Technology
Media Contact: NJ Jaeger
Expert Contact: Jeffrey M. Smith
Austrian Agency for Health and Food Safety
Corporate Communication: Univ.-Doz. Ingrid Kiefer
Tel: +43 50 555-25000; E-Mail: firstname.lastname@example.org
Austrian Study: http://www.ages.at/ueber-uns/presse/pressemeldungen/klarstellung-zu-neuen-er
Institute for Responsible Technology: http://responsibletechnology.org
Non-GMO Shopping Guide: http://www.responsibletechnology.org/DocumentFiles/144.pdf
Genetic Roulette: http://www.geneticroulette.com