To Investigate the Relationship Between In Utero Exposure to Endocrine Disruptors and Cytokine Levels in Umbilical Cord Blood

- N. Glaichenhaus -
How does a mother’s exposure to endocrine disruptors during pregnancy impact the neurodevelopment of her newborn? Insights from the French EDEN cohort.

Academy 3 highlight

Endocrine disruptors are currently found in manufactured goods and plant and animal-based foods. Most originate from the agrochemical industry and persist in the environment for many years. This project investigates the mechanisms through which endocrine disruptors have a detrimental impact on human health. As such, it fits one the major themes of Academy 3, i.e., elucidating mechanisms by which anthropogenic activities induce risks for society and the environment.

The project

Epidemiological studies have demonstrated that children born to women who have been exposed to endocrine disruptors during pregnancy have an increased risk of exhibiting neurodevelopment alterations and behavioral abnormalities. However, the underlying mechanisms by which endocrine disruptors impact neurodevelopment are unknown. Cytokines are soluble molecules that are mainly produced by immune cells in blood and peripheral tissues, and act on many cell types including those of the central nervous system. Because endocrine disruptors are known to impact the immune system, we have hypothesized that endocrine disruptors may not act directly on the brain, but rather impact cytokine levels which would, in turn, affect neurodevelopment. To test this hypothesis, we have taken advantage of the large collection of biological samples and clinical variables that were acquired in the French EDEN mother-child cohort. EDEN was set up in 2003 in French maternity clinics in Nancy and Poitiers.
Study participation was proposed to 3758 women before their 24th week of amenorrhea, and 2002 of them were eventually enrolled in the study between 2003 and 2006. Urine samples were analyzed at different times of pregnancy for the presence of endocrine disruptors in order to assess maternal exposure to these chemical compounds. Umbilical cord blood samples were collected at birth and analyzed for cytokines such as interleukin (IL)-6 and IL-17A, which are known to act on neurodevelopment (at least in rodents). Children were assessed periodically up to an age of 10 years to identify those exhibiting neurodevelopmental problems. Using multivariable statistical analysis methods, we analyzed these datasets to identify cytokines whose level in cord blood was associated with the level of endocrine disruptors in maternal urine. We found that IL-6 levels in umbilical cord blood were positively associated with exposure to Mono-3-Carboxy-Propyl-Phthalate (MCPP), a well-known endocrine disruptor present in the environment.

For the next step, we will use a statistical method known as “mediation analysis” to determine whether the detrimental impact of MCPP on neurodevelopment is explained, at least in part, by the impact of MCPP on IL-6 levels. We will also conduct similar analyses on another independent dataset. Should our results be validated, they will provide novel insights into the mechanisms by which exposure to endocrine disruptors during pregnancy impacts the neurodevelopment of the fetus.

The +

This study is one of the first to investigate the mechanisms by which endocrine disruptors impact neurodevelopment in humans. It combines biology, medical sciences and statistical analyses to assess clinical variables and biological samples collected within the frame of the EDEN Mother-Child cohort.

What’s next?

If we demonstrate that the detrimental impact of endocrine disruptors on child behavior is mediated by cytokines in the EDEN cohort, we will seek to validate our results in the FinnBrain Mother-Child cohort that consists of 3808 mother-child pairs who have been enrolled and followed in Finland since December 2011. We will apply to the ANR and European funding agencies to pursue this more ambitious work.

Project information

Scientific domain
Environmental Health
Neurodevelopment, Immunology,
Key words
Endocrine disruptors,
Immune system,
Total budget
200 k€  including :
15 k€ from Académie 3 and 60 k€ from Bureau Idex
50 k€ from Research Collaborative grant from the Agence nationale de sécurité
sanitaire de l’alimentation, de l’environnement et du travail
75 k€ from personnel costs of a tenured Inserm researcher and a UCA Professor


Project members
Glaichenhaus Nicolas
Barbara Heude
Claire Philippat

portrait Nicolas Glaichenhaus
portrait Nicolas Glaichenhaus

Nicolas Glaichenhaus

Insitut de Pharmacologie Moléculaire et Cellulaire (IPMC)

Project valorization

Publications :
In press :
  • Immune activity at birth and later psychopathology in childhood. Susana Barbosa, Olfa Khalfallaha, Anne Forhan, Cedric Galerad, Barbara Heude, Nicolas Glaichenhaus and Laetitia Davidovic. Brain, Behavior, & Immunity Health
  • Cord Serum Cytokines at Birth and Children's Anxiety/Depression Trajectories from 3 to 8 Years: The EDEN Mother-Child Cohort. Cédric Galera, Susana Barbosa, Ophélie Collet, Olfa Khalfallah, Bruno Aouizerate, Anne-Laure Sutter-Dalley, Muriel Koehl, Lucile Capuron, Judith Van der Waerden, Maria Melchior, Sylvana Côté, Barbara Heude, Nicolas Glaichenhaus, Laetitia Davidovic, on behalf of the EDEN Mother–Child Cohort Study Group, Biological Psychiatry
  • Cytokines as biomarkers in psychiatric disorders: methodological issues. Cédric Galera, Olfa Khalfallah, Susana Barbosa, Emanuela Martinuzzi, Laetitia Davidovic and Nicolas Glaichenhaus,  Chapitre d'ouvrage : Immunopsychiatry" Elsevier
  • Conference in Grenoble, October 2018: Association entre la nature et l’abondance de cytokines dans le sérum et les dimensions psycho-comportementales chez l’enfant; by Susana Barbosa, Olfa Khalfallah, Cédric Galera, Anne Forha, Barbara Heude, Nicolas Glaichenhaus, Laetitia Davidovic and the Groupe d’Etude de la Cohorte Mères-Enfants EDEN
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