Certain environmental toxins greatly decreased the fertility and sperm counts of male rat offspring through four generations, and the same could hold true for humans, stressed scientists in a new study, though the human risk hasn't yet been tested.1
Transforming Genes
Michael Skinner, PhD, director of the Center for Reproductive Biology at Washington State University, and his colleagues found that exposing rats to these toxins altered their genes that affected the reproductive function of their male offspring. The toxins were known as vinclozolin, a fungicide commonly used in vineyards, and methoxychlor, a pesticide that replaced DDT. Each of these is an endocrine disruptor; they alter the normal functioning of reproductive hormones.
While Skinner's team used higher levels of the toxins than what might normally be found in the environment, their study raises concerns about the long-term impact of exposure to these toxins on human and animal health. It's not yet known if lower levels of the toxins may also have a detrimental effect.
"It's a new way to think about disease," explained Skinner, who is also a professor of Molecular Biosciences. "We believe this phenomenon will be widespread and be a major factoring in understanding how disease develops."
Environmental Exposure Effect
In their study, the investigators exposed a group of pregnant rats to the two toxins during the period that the sex of their offspring was being determined. A second group of mice was not given the toxins so that outcomes from both groups could be compared.
The animals in the group given the toxins later produced male offspring with abnormally low sperm cells and sperm counts. The scientists found "a greater than two-fold increase" in the numbers of sperm cells that had been destroyed in that group. In addition, "sperm numbers were reduced minimally, 20%, and sperm forward [movement] was reduced about 25% to 35%" in the group given one of the toxins, Skinner and his team reported.
Same Effects Through Generations
While those males were eventually able to produce offspring of their own, their male offspring had the same defects, Skinner and his colleagues found. This persisted through all the generations tested, affecting more than 90% of the male rats involved. Skinner says this side effect of toxin exposure was expected in the first generation of rats, but not in the subsequent generations.
Further, the scientists noticed that four male rats eventually developed periodic infertility and a severely reduced sperm count. None of the rats in the group without the toxins developed infertility, they found.
These abnormalities have been thought to be related to certain abnormalities in genes, usually declining in frequency as the abnormality, or mutation, gets transferred to some children, but not others in future generations. This study, in contrast, suggests that epigenetics (eh-pih-jen-EH-tiks) plays a role in these reproductive abnormalities.
Epigenetics is a process of inheritance in which the genes inherited remain the same, but chemicals modify the way they function. While epigenetic changes have been the focus of other research,2-4 they have not been seen passing to other generations, as in this study. It appears that the influence was passed from the male rats. However, "a number of abnormal pregnancy outcomes [similar to a condition known as preeclampsia] were observed in pregnant females" in the group that received the toxins, but not in the group without them, the study team learned.
Toxins May 'Reprogram' Reproductive Cells
There are broader implications of this research besides male reproduction, Skinner and his colleagues noted. The results suggest that environmental influences could affect multiple generations in terms of inheritable diseases. Skinner says epigenetic changes could play a role in the origins of breast cancer and prostate disease, whose frequency is increasing faster than would be expected if they were the result of gene abnormalities alone.
"The ability of an environmental factor (for example, endocrine disruptor) to reprogram the germ line [cells that make the reproductive cells] and to promote a transgenerational disease state has significant implications for evolutionary biology and disease etiology," the researchers concluded.
1. Anway MD, Cupp AS, Uzumcu M, Skinner MK. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 2005 Jun 3;308(5727):1466-9.
2. Miyamoto K, Ushijima T. Diagnostic and therapeutic applications of epigenetics. Jpn J Clin Oncol 2005 Jun 1;[Epub ahead of print].
3. Laird PW. Cancer epigenetics. Hum Mol Genet 2005 Apr 15;14 Spec No 1:R65-76.
4. Sathyanarayana UG, Toyooka S, Padar A et al. Epigenetic inactivation of laminin-5-encoding genes in lung cancers. Clin Cancer Res 2003 Jul;9(7):2665-72.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
