“What also needs to be borne in mind”, continues Jean-Pierre Bourguignon, “is that during pregnancy, a nutritional imbalance because it is too rich or because it is insufficient can be stress factors, just as exposure to endocrine disrupters. We now know that the effects of these two factors are cumulative. During fetal life we programme the manner in which our energy balance will be regulated. The endocrine disrupters modify this basic system very convincingly: the run the risk, for example, of causing type 2 diabetes and obesity. But this can also influence puberty. One of our recent studies conducted on under-nourished rats during gestation showed that five days exposure to an endocrine disrupter (DES) changes the pubertal timing in tandem with a modification of the effects of leptin on the hypothalamus”.

The adoption theory

The impact of nutrition and endocrine disrupter factors seems to be particularly crucial for some young girls: those who were adopted in distant countries (Read Precocious puberty and DDT). While examining the increased number of cases of precocious puberty in young girls, the researchers suggest that their earlier-onset puberty could be the result of a combination of adversity in early life followed by richness (nutritionally-speaking) at pre-puberty and in certain cases the impact (for them or their pregnant mothers)of exposure  to chemical pollutants some of which are now banned in Europe... This is the case, for example, for children coming from countries with endemic malaria and where DDT is still used or has been widely used in the past. Boys and girls will be at a greater risk of precocious puberty in this case. In relation to Belgian children who are not exposed to these factors, the risk would be 80 times greater consider the pediatric endocrinologists.

"The moment is the poison"

Conclusions about the consequences of in-utero exposure to various pollutants and toxins have led researchers to other possible causes that are particularly important. “For a long time”, explains Professor Bourguignon, “We have examined these environmental impacts from the angle of ‘traditional’ toxicology. We were adopting the principle of Paracelsus according to which ‘the dose makes the poison’. Our research and others have shown that a change of paradigm is absolutely necessary: it is also true to say that the moment makes the poison. Thus, for example, the fetus will be sensitive to certain disrupters which, at other times of life would have no effect on the organism."

In an article soon to be published, the researchers from Liège also show that the same substance can have diametrically opposite effects, says Professor Bourguignon. In order to arrive at such a conclusion, they injected rats with different doses of bisphenol A, for a period of two weeks after the birth of these animals. In one case, it was the upper “limit”dose. This caused puberty to occur earlier. In the other case, a dose that was 200,000 times weaker, delayed puberty: the same substance given at the same time therefore had completely opposite effects according to the dose. By studying the frequency of neuropeptide secretion in the brain of the rats, it was possible to see that the brain of the animals exposed to high doses acted as though the animal was more mature, while conversely, a delay in maturation occurred with the weaker dose. If this study is important, it is so because it entirely calls into question the principle of “tolerable dose” for the organism.

"That principle, still defended by current toxicology, is not applicable to certain endocrine disrupters, Professor Bourguignon assures us. This assessment solidly shakes up of the system which we work with at the moment with regard to ‘tolerance’ of industrial products. Faced with the challenges, and in order to continue to investigate this area that could potentially have serious consequences, the endocrinologist explains that the entire genome needs to be studied to see the expression of genes and their contradictory variations according to the doses of an injected substance. In fact, a reading of current works implies that there are possible links between the environment and genetic control, with different environmental effects influencing epigenetic mechanisms.  "The possible modifications of the expression of genes during fetal life can extend to adult life and can then impact on later generations”, warns the pediatric endocrinologist.

Warn the citizens!

Potentially, the work conducted on puberty can have extremely serious implications with regard to public health. "Currently, the fetus is exposed to more than a hundred toxic chemicals including endocrine disrupters”, Professor Bourguignon reminds us. What attitude should the authorities have? Could they possibly resist the pressure from lobbies in the EU who fight for the right to be able to continue to use these substances? With regard to the states, we know that their opinions are sometimes divided with regard to the precautionary measures they decide to take. For example, in France, bisphenol A has been banned in all food. In Belgium, the authorities were content to ban baby foods.   

Another question remains to be answered in parallel with this: how to train doctors so that they can fully play a prevention role? "Currently, we can – we should – essentially say to women that pregnancy is a particularly delicate time during which the principle of precaution should be applied to the maximum”, states Professor Bourguignon. “But this precaution does not only concern pregnant women: society as a whole should be aware that by dangerously exposing the fetus, we risk creating consequences whose effects will be felt in a few decades or more. As well as products, like for example phthalates, which can lead to genital malformations, a series of substances interfere with our hormonal system and are the precursors to a deferred problem. Studies show that this does not just affect puberty and reproduction: it can also lead to cerebral problems, obesity, diabetes, metabolic syndrome, cancer …"

The delay between our current reactions –or our insufficient reactions – and processes that are happening currently could have very serious consequences. From this viewpoint, the research conducted by the teams of researchers from Liège are a useful reminder that work on the modifications and stresses on puberty go over the heads of our boys with changing voices and our young girls blossoming into young women...