Prenatal exposure to endocrine disruptors and neurodevelopment risk

Study of siblings exposed to diethylstilbestrol

2015 Study Abstract

Many endocrine disruptors are found in our environment. They act on hormonal receptors, on their action and synthesis. They may alter neuronal transmission and neuronal formation.

Exposition prénatale aux perturbateurs endocriniens et risque sur le neurodéveloppement : étude de fratries exposées au diéthylstilbestrol, UPD5 Médecine – Université Paris Descartes – Faculté de Médecine, dumas-01213114, October 7, 2015.

Image credit open archive HAL.

A lot of neurodevelopmental diseases have a growing prevalence, raising many questions about a possible association with endocrine disruptors. One of their action mechanisms may be an effect on DNA methylation of the developing brain.

Objectives
To study neurodevelopmental characteristics and the epigenetic signature of patients exposed in utero to diethylstilbestrol. To identify differentially methylated regions in neurodevelopmental related genes, which could lead to a psychiatric vulnerability.

Materials and Methods
We recruited 75 siblings from 31 families, in which at least one member was exposed in utero to diethylstilbestrol. A psychiatric evaluation was assessed with standardized questionnaires. We used the Infinium HumanMethylation450 BeadChip and analyzed the methylation variations of 411 947 CpG loci.

Results
We found clinical differences in non-specific psychiatric symptoms and in neurological soft signs, such as lateralization, associated with the exposure. We found several biological pathways in which methylation modifications were associated to diethylstilbestrol exposure. These pathways are implicated in neurodevelopmental pathways, general metabolism and oncogenesis mostly.

Conclusion
Prenatal diethylstilbestrol exposure seems associated with non-specific psychiatric symptoms, lateralization abnormalities and methylation alterations in genes that participate to pathways known to be involved in psychiatric diseases, notably in neurotransmitters signalization.

Note
The 100 pages complete study – THÈSE POUR LE DIPLÔME D’ÉTAT DE DOCTEUR EN MÉDECINE – is available (free access) in French language on HAL archives-ouvertes.

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