There has been a lot of debate about the safety of EDCs - endocrine disrupting chemicals that act similarly to hormones that we naturally produce. For example, phthalates or BPA (bisphenol A) can act like testosterone or estrogen, respectively. BPA is commonly found in household products like food and drink containers, phthalates are sometimes used in cosmetics or other products, and these chemicals might be connected to rising problems in public health, like low fertility. In a new study published in Scientific Reports, researchers at ETH Zurich and the Technical University of Munich used an animal model to show that even at extremely low levels, modifiable changes in DNA, called epigenetic tags, are altered in pregnant sows. Those changes were still detectable after their offspring reached adulthood.
"EDCs, especially estrogens, are highly effective even at very low doses," said Susanne Ulbrich, Professor of Animal Physiology at ETH Zurich. The strength of the effect depends on when the exposure happens. "For example, the body is particularly susceptible to external disruptive hormonal influences during the embryonic phase of early pregnancy,” Ulbrich explained.
EDCs were administered to pregnant pigs in their food or drinking water over the ten days after fertilization, or entire pregnancies. The acceptable human intake was reflected in one experimental dose; the scientists also tested the effects of levels of “no observable effect,” a high dose, and no dose.
Gene expression was assessed in the tissues of the sows and the fetal and adult tissue of offspring. Of 57 genes related to estradiol, about two dozen were impacted by estradiol. The genes that were identified tend to control the cell cycle or tumor growth.
The team also saw epigenetic changes in some genes, both in embryos, one-year-old, and adult offspring. The chemical tags that get added to or removed from genes, which exert a so-called epigenetic effect, can have a big impact on gene regulation and by extension, cell function.
"We didn't find any serious impact on the health of the adult offspring; we saw only slight changes, such as in bone density and the ratio of fat to muscle mass," Ulbrich explained. The long-term effects of those epigenetic changes remain unclear. It’s also not known if the many EDCs that humans probably experience every day are exacerbating the effect.
"There is an urgent need to observe this phenomenon over several generations in a long-term study," continued Ulbrich. "Epigenetic changes can emerge within just one generation, but in certain circumstances, they will continue to be transmitted to succeeding generations. We can already clearly demonstrate that hormones, even after a brief exposure period and in very small amounts, can have a measurable effect.”
Ulbrich is an expert in reproductive physiology, so these results have led her to call for a new evaluation of the safety of EDCs. Pigs that experience hormone changes during pregnancy closely mirror what is seen in humans, suggesting that these results apply to us. They may, in fact, be a better model for this system than mice.
"At the moment, recommended threshold levels are probably too high," noted Ulbrich. Even when the estrogen dose was very small, the team could easily see evidence that epigenetic changes had occurred. "How exactly that resulted in the changes and what impact these changes will have in the long run requires closer study. The sensitivity of embryos in the early days of pregnancy should under no circumstances be underestimated,” she added.
Sources: AAAS/Eurekalert! Via ETH Zurich, Scientific Reports