IS IN UTERO EXPOSURE TO FEMALE XENOHORMONES HARMING THE NEURODEVELOPMENT OF CHILDREN AND GRANDCHILDREN? A FRENCH NATIONAL EXPERIENCE AND OTHER LESSONS FROM THE PAST

For decades, synthetic hormones have been administered to millions of pregnant women to prevent miscarriage or premature birth without prior robust studies on their potential toxicity. The example of diethylstilbestrol, a synthetic estrogen, is emblematic. In this review, first, we discuss the neuropsychological impact of xenoestrogens on children exposed in utero (schizophrenia, bipolar disorders, anxiety and severe depression, autistic spectrum disorders). Some studies indicate that these xenohormones act through an epigenetic mechanism by promoting the hypermethylation of genes implicated in neurodevelopment. Second, similar neuropsychological effects have been observed in children exposed in utero to progestins. Their mechanisms of action involve the estrogen receptors alpha and beta expressed in the amygdala. Third, epigenetic mechanisms are involved in the multigenerational effects observed in the third generation (i.e. the grandchildren of the women who took xenohormones during pregnancy) and in few fourth-generation adolescents. These findings led to the hypothesis of a transgenerational effect, raising the alarm concerning the other uses of these endocrine disruptors (particularly for contraception).