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Review
. 2024 Apr 23;25(9):4599.
doi: 10.3390/ijms25094599.

The Impact of the Aryl Hydrocarbon Receptor on Antenatal Chemical Exposure-Induced Cardiovascular-Kidney-Metabolic Programming

You-Lin Tain  1   2   3 , Chien-Ning Hsu  4   5
Affiliations
Review

The Impact of the Aryl Hydrocarbon Receptor on Antenatal Chemical Exposure-Induced Cardiovascular-Kidney-Metabolic Programming

You-Lin Tain et al. Int J Mol Sci. .

Abstract

Early life exposure lays the groundwork for the risk of developing cardiovascular-kidney-metabolic (CKM) syndrome in adulthood. Various environmental chemicals to which pregnant mothers are commonly exposed can disrupt fetal programming, leading to a wide range of CKM phenotypes. The aryl hydrocarbon receptor (AHR) has a key role as a ligand-activated transcription factor in sensing these environmental chemicals. Activating AHR through exposure to environmental chemicals has been documented for its adverse impacts on cardiovascular diseases, hypertension, diabetes, obesity, kidney disease, and non-alcoholic fatty liver disease, as evidenced by both epidemiological and animal studies. In this review, we compile current human evidence and findings from animal models that support the connection between antenatal chemical exposures and CKM programming, focusing particularly on AHR signaling. Additionally, we explore potential AHR modulators aimed at preventing CKM syndrome. As the pioneering review to present evidence advocating for the avoidance of toxic chemical exposure during pregnancy and deepening our understanding of AHR signaling, this has the potential to mitigate the global burden of CKM syndrome in the future.

Keywords: aryl hydrocarbon receptor; cardiovascular disease; chemical; chronic kidney disease; developmental origins of health and disease (DOHaD); dioxins; hypertension; metabolic syndrome; prenatal exposure.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Schema outlining the structure of the aryl hydrocarbon receptor.
Figure 2
Figure 2
Classical and non-classical AHR signaling pathways.
Figure 3
Figure 3
The AHR connects antenatal chemical exposure to CKM programming and reprogramming.
See this image and copyright information in PMC

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