Posted by: Sarah Mosko
In pregnant women, exposure today to endocrine-disrupting substances common in everyday plastics might not only be adversely affecting the health of their fetuses, but the health and fertility of their future great grandchildren might also be at risk, according to a laboratory study just published in January.1 The health risks are not handed down via changes to the genetic DNA code (i.e. gene mutations), but rather through a parallel biological scheme of coding known as “epigenetics.”
Traits are passed from one generation to the next through two distinct but interacting vehicles of inheritance. The genes that make up our DNA were once thought to contain the entire blueprint for all inherited traits. For some time, however, scientists have understood the critical role of another coding system that literally sits atop the DNA and instructs genes to turn on or off. Because all cells in a given animal or human have the same DNA sequence as the original fertilized egg and sperm, another mechanism is needed to explain how cell differentiation occurs during development so that a heart cell, for example, ends up so different from, say, a brain or skin cell.
The prefix “epi” means “on top of,” hence the name epigenome referring to this supplementary code affixed to DNA that orchestrates development by regulating gene expression. For some time now, scientists have known that a person’s epigenome is also involved in establishing susceptibility to diseases because whether or when certain genes are expressed can determine if a person will fall victim to some diseases.
It is also understood that the epigenome is not fixed during a person’s lifetime, but rather can be altered by environment (chemical exposure or even diet, e.g.). However, it is only recently that scientists have clued into the fact that changes to the epigenome acquired during a lifetime can be passed from one generation to the next right along with the genetic DNA code within sperm or egg cells. This means that environmentally-mediated modifications in susceptibility to disease have the potential to get passed along too.
Previous studies documented that the agricultural fungicide vinclozolin, when administered to pregnant female rodents, induced permanent epigenetic changes to the sperm of developing fetuses that were replicated and passed on to subsequent generations. The epigenetic changes were deleterious in that they promoted certain adult-onset diseases.
The present study, conducted at Washington State University, focused instead on two known types of endocrine-disrupting chemicals used in mass-produced plastics, BPA (bisphenol-A) and phthalates. BPA is a component of both polycarbonate plastics and the epoxy resin lining of most canned foods/beverages. Exposure during fetal life is known, through animal studies, to impact a wide spectrum of adult-onset diseases, including polycystic ovaries, prostate disease, abnormal mammary gland development, behavioral hyperactivity and aggressiveness, and altered glucose metabolism. Phthalates are softening agents common in PVC (polyvinyl chloride) plastics and also a common ingredient of beauty products and adhesives. Phthalates have been linked to many derailments in the normal development of both male and female reproductive systems, resulting in decreased fertility in both sexes.
What did they do?
Pregnant female rats (and consequently their fetuses) were exposed to mixtures of BPA and two phthalates (DEHP and DBP) over a one-week period spanning the critical window in fetal development when gonadal sex is determined. The incidence of adult-onset diseases of the testis, prostate, ovary and kidney were determined in those fetuses and the grandchildren of those fetuses (i.e. the great grandchildren of the exposed pregnant females) once they reached adulthood.
In understanding this study, it is important to appreciate that the fetuses’ future grandchildren are the first generation where abnormalities cannot be attributed to a direct effect of chemical exposure to any of the fetuses’ tissues, but rather must have been handed down through undesirable epigenetic changes to the exposed fetuses’ sperm or eggs which remained fixed and passed on. Prior research has shown that gene mutations are not involved.
The best understood epigenetic mechanism is “DNA methylation” where chemical fragments called methyl groups (–CH3) attach or detach to DNA and, in doing so, regulate gene expression. Furthermore, various environmental chemicals are known to alter the pattern of methylation. In the present study, the researchers looked for enduring and heritable epigenetic changes resulting from exposure to BPA and phthalates by examining the methylation pattern of sperm DNA from both the exposed fetuses and those fetuses’ grandchildren.
What did they find?
As adults, both the originally exposed fetuses and their grandchildren showed increases in testis disease, obesity, ovarian disease, and shifted onset of puberty. The original fetuses also showed increases in kidney and prostate disease, but those conditions were not inherited by their grandchildren. The type of disease abnormalities detected were not tumors per se, but rather other tissue abnormalities, like polycystic ovaries or decreased sperm production.
The researchers were also able to identify several epigenetic methylation changes to the sperm DNA of the chemically exposed fetuses that were similarly passed to their grandchildren and thought to be involved in promoting the diseases.
The central finding of this study is that, in rats, short-term fetal exposure to a mixture of chemicals found in plastics has the potential of promoting adult-onset diseases that, in turn, are handed down to subsequent generations. The inheritance is not through gene mutations, but rather through epigenetic changes (epimutations) to the developing fetus’ sperm DNA which are not reset with the next generation but rather replicated and passed on.
Rats are mammals and, as such, are useful models for gaining insight into how environmental toxins can affect humans. This study suggests that plastics we are interacting with today might have the legacy of making our great grandchildren, and perhaps generations beyond, more susceptible to a whole host of diseases when they grow up.
The chemical doses used in this study were low for animal studies but admittedly higher than the levels to which humans are routinely exposed. Nevertheless, widespread human contamination with both BPA and phthalates is well-documented. Furthermore, human exposure to these chemicals likely occurs continuously throughout our lifetimes, given the near universal role of plastics in human activities, from dining and driving cars to computer work and housecleaning. So though the results of this study do not provide any real measure of the risk to humans associated with our current levels of exposure to endocrine-disruptors in plastics, they certainly do raise the possibility that humanity’s love affair with plastics might have lasting effects on the health and fertility of future generations.
This speculation is in line with a growing body of evidence that endocrine disrupting chemicals now widespread in our environment are contributing to the lower sperm counts, more ovarian disease and increasing rates of obesity and infertility frequently seen in human populations (see Discussion).
There are already literally hundreds of studies documenting direct health effects in lab animals and even humans of fetal exposure to BPA and phthalates. We have been playing Russian roulette with these and literally tens of thousands of other synthetic chemicals allowed into commerce since World War II without prior health safety testing. Chemicals in the United States are still regulated by antiquated legislation (Toxic Substances Control Act of 1976) which allows industry to market chemicals without proving their safety first.
For the sake of our own health and that of our progeny, not only do we need to continue mapping out how endocrine-disrupting chemicals like BPA and phthalates interact with the very apparatus of inheritance, but we also need to insist that the federal government adopts a precautionary approach to chemicals regulation that requires thorough vetting of chemicals for safety to humans and other life forms before being allowed into commerce.
1M Manikkam et al. Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations. PLOS ONE, Jan. 2013.