CE34 - Contaminants, écosystèmes et santé

Maternal Exposure to Mixed Organics pollutants: placental epigenetic marks and Risk assessment for offspring’s health – MEMORI

Submission summary

The general population, including pregnant women, is exposed to endocrine disruptors, including phthalates and synthetic phenols (PSPs). These compounds are used in a large number of consumer products such as plastics, epoxy resins, cosmetics and food packaging, leading to daily exposure of pregnant women through ingestion, inhalation and/or dermal contact. This exposure represents a high risk for the ante- and post-natal health of the offspring.
The objectives of MEMORI are to evaluate whether maternal ingestion of a mixture of PSPs, suspected to affect placental weight and birth weight, disrupts placental function and induces placental specific signatures of this exposure, affecting the phenotype of the offspring, with sex-specific responses.
To reach these translational and intergenerational objectives, MEMORI program will rely on 3 complementary approaches: 1) the SEPAGES mother-child cohort, dedicated to the monitoring of chemical exposure - especially PSPs - during pregnancy, and their effects on the health of children up to the age of 5. This cohort also includes biological samples from mothers and their children; 2) an in vitro model of trophoblastic cells isolated from human placenta at term, allowing to decipher the effects and molecular mechanisms of PSPs; 3) a biomedical rabbit model, relevant in terms of placentation and steroid production by the gonads during fetal life, similar to that of humans. This model is also appropriate to study germ cell orientation to the male or female pathway, fetal toxicity and long-term effects in adult offspring.
Using the in vivo animal model, the effects of maternal exposure, by ingestion, to a mixture of PSPs, mimicking the exposure of the mothers of the SEPAGES cohort, will be evaluated on feto-placental development and growth but also on the postnatal phenotype, in particular cardiometabolic status and gonadal function, taking into account the sex of the offspring. At the same time, the SEPAGES cohort will continue to follow the children up to the age of 7, including biometric measurements. The human trophoblastic cell model will allow us to study the mechanism of action of PSP as well as placental epigenetic signatures specific to exposure to these compounds (single or mixed). The epigenetic signatures established in trophoblastic cells in vitro will be investigated and validated in rabbit and human placentas from the SEPAGES cohort. Finally, the placental marks will be correlated to postnatal phenotypes identified in the rabbit model, allowing the extrapolation of potential phenotypic risks to children over the longer term.
These results will be crucial as they will allow national or European public authorities (ANSES, EFSA) to implement recommendations during this sensitive period of pregnancy.

Project coordination

Anne COUTURIER-TARRADE (Biologie de la Reproduction, Environnement, Epigénétique & Développement)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

IAB Institut pour l'Avancée des Biosciences
UMR1331 INRAE- TOXALIM
BREED Biologie de la Reproduction, Environnement, Epigénétique & Développement

Help of the ANR 513,233 euros
Beginning and duration of the scientific project: February 2022 - 48 Months

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