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Hormone-active substances influence the genes
It has long been discussed what effects so-called hormone-active substances such as the plasticizer bisphenol A (BPA) have on human health. For example, possible disorders in child development and impairments of fertility are known. In a current study, a research team from ETH Zurich and the Technical University of Munich was able to demonstrate that hormone-active substances also lead to a change in gene expression that affects even the next generation - at least in pigs.
In the experiments on pigs, the research team was able to demonstrate for the first time that the administration of extremely small amounts of a hormone-active substance can lead to epigenetic changes in the genetic makeup of the dams, and at the same time the affected embryos show changes that can still be detected even in adult offspring. The scientists suspect similar effects in humans. They have published their study results in the scientific reports.
What effect do hormonal disturbances have?
Hormone-active substances can be found in many everyday products such as phthalates or BPA as plasticizers in plastic products. It has not yet been finally clarified which health risks can arise from these substances. The body is particularly sensitive to external hormonal disturbances, for example in the embryonic stage at the beginning of pregnancy, explains Susanne Ulbrich, Professor of Animal Physiology at ETH Zurich, in a press release on the latest study results.
Very effective even in low doses
In their current study, the researchers examined in pregnant sows what effects hormonally active substances - in this case a body's own estrogen as a model substance - have on the genetic makeup of the mother pig and the offspring. "Hormone-active substances, especially estrogens, are extremely effective even in very low doses," says Prof. Susanne Ulbrich. This applies in particular to certain time windows in embryonic development. The researchers took a closer look at such a time window in their experiments.
Targeted administration of hormone-active substances
Different doses of 17-beta-estradiol (a natural estrogen) were administered daily to the mother animals via the feed. The absorption of hormone-active substances in drinking water or food was simulated. In some animals this occurred in the whole gestation period, in others only during the first ten days after fertilization.
Different doses examined
The lowest dose in the tests corresponded to the equivalent of the daily dose allowed for humans (0.05 micrograms per kilogram of body weight), the study authors report. In addition, a dose of ten micrograms per kilogram of body weight and a high dose of 1,000 micrograms per kilogram per day had been tested. The high dose roughly corresponded to the case of accidentally taking the contraceptive pill (birth control pill) during the start of pregnancy, the researchers explain.
Around two dozen genes with changes
Furthermore, the scientists examined gene expression and the epigenetic changes in various tissues of the mother sows and in the successor generation, both in ten-day-old embryos (blastocysts) and in one-year-old female offspring. For comparison, animals that did not receive estradiol were also examined. The researchers found that out of the 57 genes related to estradiol, tissue-specific changes in expression, depending on the dose, occurred in around two dozen of the genes examined.
Changes in embryos are also noticeable
The majority of genes affected included those that control the cell cycle or suppress the growth of tumors, the researchers report. These changes were most pronounced in the luteal body and in the endometrium, as well as in the heart and skeletal muscles of the mother sows. The scientists were also able to identify epigenetic changes in a few selected genes of the sows' liver tissue. Similar changes to these genes also occurred in the embryos and were found in adulthood. In the female yearlings, the epigenetic pattern of these genes was still changed.
Minimal changes with far-reaching effects
According to the study authors, epigenetic changes arise, for example, from the addition or removal of small chemical groups such as so-called methyl groups at certain points in DNA. This could change the expression of the affected genes and thus the function of the cell.
Long-term consequences remain unclear
According to Prof. Ulbrich, the researchers found only very slight changes, for example in the bone density and the ratio of fat to muscle mass in the adult offspring, and no serious health effects. But what long-term effects the epigenetic changes can have remains open. It is also unclear whether the interaction of different hormone-active substances to which humans are exposed on a daily basis can exacerbate the situation, the researchers report.
Changes inheritable over generations?
Prof. Ulbrich emphasizes that further studies urgently need to be monitored over several generations for a long time to see what effects the hormone-active substances have. Because epigenetic changes can only occur in one generation, but they may be permanently transferred to the next generation, the expert continues. It is already clear that “hormones have a demonstrable effect after only a short exposure time and in very small amounts.”
Don't underestimate the sensitivity of embryos
The observed epigenetic changes were clearly due to exposure to a hormone-active substance and were evident even in the smallest amounts. "How exactly the changes came about and what they will do in the long term will have to be researched in more detail in the future" the director of studies continues. The sensitivity of the early embryo should not be underestimated.
New limits required?
In view of the results of the investigation, the amounts of the daily doses allowed for hormone-active substances should be adjusted urgently, because the hormonal changes in pigs during pregnancy are quite similar to those in humans, according to the study leader. The results of the study are easily transferable to humans and may even be more meaningful than, for example, those from a study in mice. "The current recommendations and limit values are probably too high," the expert concluded. (fp)