CYTOPOL

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 24^th 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.