An update on the progress of the collaborative project on prenatal exposure to phenols and dysregulation of the hypothalamic–pituitary–adrenal axis in two European cohorts: BiSC (Barcelona, Spain) and SEPAGES (Grenoble, France)

Synthetic phenols, recognized as endocrine-disrupting chemicals, exhibit widespread exposure within the general population. While toxicological evidence is accumulating on their potential to disrupt the hypothalamic–pituitary–adrenal (HPA) axis—a key regulator of the body’s adaptive response to stress—epidemiological studies with sufficient sample size and rigorous methodologies to assess such effects in humans are lacking. The HyPAXE project co-led by Dr. Claire Philippat (INSERM, Grenoble, France) and Prof. Jordi Sunyer (ISGlobal, Barcelona, Spain) and funded by the French Agence Nationale Sécurité Sanitaire Alimentaire Nationale (ANSES) was designed to fill this gap and shed light on the associations between exposure to synthetic phenols during pregnancy and the production of adrenal and reproductive hormones.

In this large study involving 1,137 participants from Grenoble (France) and (Barcelona) Spain we relied on repeated urine samples to assess phenol exposure during two trimesters of the pregnancy. Hormones related to the HPA axis were measured in maternal hair, enabling the evaluation of hormone production over an extended period (weeks to months). These state of the art methodologies aim to minimize exposure misclassification and bias, addressing limitations of previous studies relying on spot phenol and hormone measurement.

Our findings present compelling evidence that exposure to bisphenol S, a chemical introduced as a replacement for bisphenol A, adversely affects maternal corticosteroid hormone production during pregnancy. Additionally, associations were observed for parabens (propyl- and methylparaben), commonly used as preservatives in personal care products and food. These results offer valuable insights into the underlying mechanisms of phenols’ deleterious effects on children’s health, as dysregulation of the HPA axis may lead to overexposure of the developing foetus to glucocorticoids, affecting its long-term development and health.

The implications for public health are substantial, as disruptions in the equilibrium between steroid hormones during pregnancy can affect both maternal health and foetal development. If followed by public policy efforts to reduce phenol exposure, these results have the potential to bring about significant improvements in public health, considering the widespread exposure to phenols in the general population and their short turnover in our bodies.

The analysis of the data collected under the HyPAXE project is now completed and the work has been submitted for publication.

This post has been written by Paulina Alicja Jedynak, postdoctoral fellow at the BiSC Project.