From cohorts to molecules: Adverse impacts of endocrine disrupting mixtures

Abstract

Convergent evidence associates exposure to endocrine disrupting chemicals (EDCs) with major human diseases, even at regulation-compliant concentrations. This might be because humans are exposed to EDC mixtures, whereas chemical regulation is based on a risk assessment of individual compounds. Here, we developed a mixture-centered risk assessment strategy that integrates epidemiological and experimental evidence. We identified that exposure to an EDC mixture in early pregnancy is associated with language delay in offspring. At human-relevant concentrations, this mixture disrupted hormone-regulated and disease-relevant regulatory networks in human brain organoids and in the model organisms Xenopus leavis and Danio rerio , as well as behavioral responses. Reinterrogating epidemiological data, we found that up to 54% of the children had prenatal exposures above experimentally derived levels of concern, reaching, for the upper decile compared with the lowest decile of exposure, a 3.3 times higher risk of language delay.

Benchmarking brain organoid recapitulation of fetal corticogenesis

“…BO are thus becoming central to the investigation of how genetic vulnerabilities or environmental perturbations can alter physiological neurodevelopment and seed the unfolding of psychiatric and neurological conditions 1,2 . As we and others recently demonstrated, the exposure of specific windows of vulnerability is proving of particular value, highlighting how temporally defined or even transient alterations in neurodevelopmental trajectories can bring about major mental health outcomes, from language delay to ASD [3][4][5] . Indeed, a growing body of literature testifies to the edge that BO are bringing to the modelling of complex neuropsychiatric disorders, from autism spectrum disorder to schizophrenia, bipolar disorder and beyond [6][7][8] .…”

A Mixture of Endocrine Disrupting Chemicals Associated with Lower Birth Weight in Children Induces Adipogenesis and DNA Methylation Changes in Human Mesenchymal Stem Cells

“…These mixtures have been further studied in experimental settings [45][46][47]. In the present study, we evaluated the effects of an EDC mixture associated with lower birth weight (Mix G1) on adipogenesis and DNA methylation patterns in human mesenchymal stem cells (hMSCs).…”

The EU chemicals strategy for sustainability: an opportunity to develop new approaches for hazard and risk assessment

“…For instance, integration of exposure assessment, epidemiological evidence and experimental approaches can be used to establish links between exposure and negative health outcomes. This was shown in a recent study (Caporale et al 2022 ) that established mechanistic and correlative evidence for an association of in utero exposure to mixtures of endocrine disruptors and learning disabilities in children.…”