‘DDT risk goes down generations’
Study finds fathers’ exposure to toxins might have health consequences for their children
Fathers exposed to environmental toxins, notably DDT, might produce sperm that could have health consequences for their offspring, according to the findings of a landmark study.
The decade-long research examined the impact of DDT on the sperm epigenome of Greenlandic Inuit and South African Vhavenda men.
The team of researchers from Mcgill University, the University of Pretoria and Université Laval concluded toxins in the environment, particularly DDT, modify the sperm epigenome at sites potentially transmitted to the embryo at conception.
The researchers said their study, published in the journal Environmental Health Perspectives, signals potential reproductive and health complications in humans — now and for future generations.
Epigenetic changes were found in genes that are involved in fertility, embryo development, neuro-development and hormone regulation.
These alterations correspond to the higher levels of birth defects and increased incidence of diseases, including neuro-developmental and metabolic, that occur in Ddtexposed populations.
Transmitting disease
Nearly 20 years ago, the first research study, using a rodent model, showed that exposure to a toxicant endocrine-disrupting chemical altered the heritable layer of biochemical information in the sperm, the epigenome. This changed fertility and led to disease across rodent generations in unexposed animals.
Millions of dollars have been poured into animal studies to better understand how such exposure can transmit disease through the epigenome across generations.
These studies confirmed the phenomena known as “epigenetic inheritance”, where environmental exposures alter the sperm epigenome, a biochemical layer of information that controls how the DNA is used to express genes during sperm production and in the developing embryo.
This epigenetic control of gene use includes DNA methylation and histone proteins. Whether such exposures act similarly in humans was unknown.
“The more DDE you’re exposed to, the higher the chromatin or DNA methylation defects are in the sperm,” said Ariane Lismer, of Mcgill University, the study’s lead author.
“Secondly, there was an enrichment of regions that were changed in sperm that are predicted to retain some of their chromatin marks in the pre-implantation embryo, and that led us to think that these regions might escape epigenetic reprogramming and have a direct role in regulating embryo gene expression.”
If they’re altered in sperm and transmitted to the embryo — which Lismer’s work has shown is possible in mice — the regions that are Ddesensitive in sperm “might be having an impact directly in the embryo”.
Disruptive chemicals
While it is generally understood that women should avoid exposure to environmental contaminants because toxins can make their way into embryos, research on how a father’s exposure and his sperm might also be changed through the epigenome has been scant.
The study aimed to assess the sperm epigenome to specific toxicants between geographically diverse populations, said lead author Tiaan de Jager, the dean of the faculty of health sciences and professor in environmental health at the School of Health Systems and Public Health at the University of Pretoria.
“We looked specifically at the insecticide DDT, which is used for malaria vector control, but it’s relevant to other endocrine-disrupting chemicals.”
DDT, in addition to its toxic effect, is an endocrine-disrupting chemical, or a hormone disruptor.
“The body will recognise DDT as if it’s the female hormone oestrogen and the breakdown product or metabolite [of DDT], DDE, is a potent anti-androgen.
“So, that would block the androgen — the male receptor — so the body would think, ‘Okay, there’s enough testosterone,’ and stop producing it but, in the meantime, it’s this environmental chemical that’s blocking the receptor and all those things are now affecting the hormone balance in the body.”
Father’s exposure
De Jager said scientific literature and animal studies have shown “we should not ignore the father’s contribution because, “when we talk DNA or genetics, the father is contributing 50% through the sperm”.
“And then we started to see that some of these effects might be associated through paternal contributions — from the father’s side —because the mother might not have been exposed to some of these things but the father was.”
This is the first human study to confirm there is a trans-generational paternal effect through the epigenome. “In the next generation, and it might be the second generation, we might see some of these health effects and it’s due to the changes in the epigenome of the sperm coming from the father’s side.”
But it’s not straightforward, “as in ‘I’ve been exposed to compound x at this concentration now I’m going to be infertile or have cancer or whatever the case may be,” De Jager said, pointing out that the health effects, and the potential to develop them, are influenced by a person’s genetic composition and the environmental contribution.
Malaria control
Despite the Stockholm Convention, a global treaty that aims to protect human health and the environment from the effects of organic pollutants, the government has special permission to use DDT for malaria control. The use of DDT for indoor spraying for malaria control is very controversial, De Jager said. Although other chemicals are in use, DDT is still used in some areas, when needed.
These pollutants can move across vast distances from the Southern Hemisphere to the Northern Hemisphere through the “grasshopper effect”. They evaporate with warm air and return to Earth with rain and snow in the colder areas of the globe where they persist in the Arctic food chain.
The exposure of human and animal populations to DDT is reportedly increasing with global warming.
“There really is a pressing need to find alternative ways to control malaria, and to put those in place, such as vaccines and alternative pesticides, because here we’re showing the DDT is impacting not only the health of the exposed generation, but potentially the next generation as well,” said Sarah Kimmins, who led the research as a professor of pharmacology and therapeutics at Mcgill University.
“I always say that while we, and other countries, are still dependent on the use of DDT, we should look at safer alternatives and be innovative in our approach to get to elimination,” De Jager added.
“The reality is people, especially young children and pregnant women, are still dying from malaria. We cannot afford for people in malaria-endemic regions to refuse [the] spraying of their houses, as it will increase their risk of getting malaria.”
While the study focuses on DDT exposure, Kimmins said it is not a leap to suggest that exposure to more common household endocrine disruptors, such as those found in cosmetics and personal care items, could act similarly.
In the food chain
De Jager explained that research in the north of Canada has shown similar health effects associated with endocrine-disrupting exposure.
“Children developed chronic middle-ear infections and all sorts of things. They started to investigate and what they found was that these men have high concentrations of DDE levels — the breakdown product of DDT,” yet DDT was never sprayed there.
De Jager said generally there would be no reason to spray DDT in the Arctic region because it’s a snowy region. However DDT has a long life of about 60 years, and through the atmosphere and the environment, ends up in the polar Arctic regions.
Here it accumulates in fish and seals because it binds to fatty tissue and that’s what people eat.
“And that helped us to say, ‘Okay, these people are from a totally different genetic background but are being exposed to this,’ and that helped us to identify the epigenetic changes that’s the same between the population and that resulted from these exposures.”