Hormone-active substances such as phthalates and BPA harm our genes

Hormone-active substances affect the genes

For some time already, there has been a discussion about what effects hormone-active substances such as the plasticizer bisphenol A (BPA) have on human health. For example, possible disorders of child development and impairment of fertility are known. In a recent study, a research team from ETH Zurich and the TU Munich has now shown that hormone-active substances also lead to altered gene expression, which affects even the next generation - at least in pigs.

In experiments on pigs, the research team was able to demonstrate for the first time that even the administration of extremely small amounts of a hormone-active substance can lead to epigenetic changes in the dams of the dams, and at the same time the affected embryos have changes that are still detectable even in adult offspring. The scientists also assume similar effects in humans. Their study results have been published in the scientific journal "Scientific Reports".

Hormone-active substances such as BPA, according to a recent study can also lead to significant changes in the genes. (Image: Zerbor / fotolia.com)

What effect do hormonal interferences have??

Hormone-active substances are found in many everyday products such as so-called phthalates or BPA as plasticizers in plastic products. The health risks posed by these substances have not yet been conclusively clarified. For example, the body reacts "particularly sensitively to hormonal disturbances from the outside 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 current study results.

Even in low dosages very effective

In their latest study, researchers at pregnant sows investigated the effects of hormone-active substances - in this case an endogenous estrogen as a model substance - on the genotype 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. Such a time window, the researchers have considered in their experiments.

Targeted administration of hormone-active substances

Each day, the mothers were fed different doses of 17-beta-estradiol (a natural estrogen) through the diet. Thus, the intake of hormone-active substances via drinking water or food was simulated. In some animals this was done during the whole pregnancy, in others only during the first ten days after fertilization.

Various dosages studied

The lowest dose in the experiments 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 daily dose of 10 micrograms per kilogram of body weight and a high dose of 1,000 micrograms per kilogram per day were tested. The high dosage was similar to the case of accidental ingestion of the contraceptive pill (contraceptive pill) during the onset of pregnancy, the researchers explain.

About two dozen genes with changes

The researchers also studied gene expression as well as epigenetic changes in various tissues of the sows as well as in the subsequent generation, both in ten-day-old embryos (blastocysts) and one-year-old adult female offspring. For comparison, animals that did not receive estradiol were also tested. The researchers found that, depending on the dose, of the 57 genes related to estradiol, tissue-specific changes in expression occurred in about two dozen of the genes studied.

Changes also detectable in embryos

Most of the affected genes included those that control the cell cycle or suppress the growth of tumors, the researchers report. These changes were most pronounced in the corpus luteum and uterine lining as well as in the heart and skeletal musculature of the mother sows. The scientists also found epigenetic changes in a few selected genes of the liver tissue of the sows. Similar changes in these genes have also occurred in the embryos and found until adulthood. In female yearlings, the epigenetic pattern of these genes was still altered.

Minimal changes with far-reaching effects

According to the study authors, epigenetic changes occur, for example, through the addition or removal of small chemical groups, such as so-called methyl groups, in certain parts of the DNA. This could alter the expression of the genes involved and thus the function of the cell.

Long-term consequences remain unclear

According to Prof. Ulbrich, the researchers have found only very slight changes, for example, 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 a combination of different hormone-active substances that humans are exposed to daily, the situation can aggravate, the researchers report.

Embryos are particularly susceptible to hormonal imbalances and, according to the current study, may experience changes in their genes throughout their lifetime. (Image: unlimit3d / fotolia.com)

Changes inheritable over generations?

In further investigations it is urgently necessary to observe for several generations what effects the hormone-active substances have, emphasizes Prof. Ulbrich. Because epigenetic changes can arise in just one generation, but they may be permanently transferred to the next generation, the expert continues. It is already clear "that hormones have a detectable effect after only a short exposure time and in very small amounts."

Do not underestimate 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. "Exactly how the changes have come about and what they will do in the long term will need to be explored more closely in the future"; the study director continues. However, the sensitivity of the early embryo should by no means be underestimated.

New limits required?

In view of the results of the study, the quantities of daily doses allowed for hormone-active substances should urgently be adjusted, as the hormonal changes in pigs during pregnancy are quite similar to those of humans, according to the study leader. The results of the study are well transferable to humans and possibly even more meaningful than, for example, those from a study in mice. "The current recommendations and limits are probably too high," the expert said. (Fp)