Maternal Di(2-ethylhexyl) Phthalate Exposure Increases the Risk of Congenital Heart Disease in Mice Offspring

Overview

Journal Pediatr Res

Specialties Biology
Pediatrics

Date 2025 Mar 16

PMID 40089607

Authors

Haiqun Shi

Zehua Zhang

Anna Shen

Tong Ding

Rui Zhao

Yan Shi

Jianyuan Zhao

Ke Cai

Feng Wang

Affiliations

Soon will be listed here.

Abstract

Abstrct: BACKGROUD: Epidemiological data suggest that maternal occupational exposure to mixed phthalates comprising di(2-ethylhexyl) phthalate (DEHP) increases the risk of congenital heart disease (CHD). In this study, we used mice as an animal model to validate impact of first-trimester DEHP exposure on the risk of CHD in offspring, to elucidate the possible mechanisms and to provide a potential feasible intervention.

Methods And Results: Eight-week-old C57BL/6J pregnant mice were randomly divided into standard and DEHP diet groups. The incidence of CHD in DEHP diet group offspring was up to 14.41% observed via Hematoxylin-eosin (HE) staining. Quantitative PCR analysis revealed that expression of key genes involved in cardiogenesis were suppressed at the transcriptional level, which may be due to decreased nuclear translocation of p65. The inhibition of DEHP on key genes was rescued to some extent by choline through driving p65 into nuclear. In the mice, supplementation of choline during DEHP exposure reduced the incidence of CHD in offspring from 14.41% to 4.63%.

Conclusions: Our study demonstrates that mice first-trimester DEHP exposure significantly increases the risk of CHD in the offspring via inhibiting mRNA levels of key genes in cardiogenesis, and choline could protect against the pathogenesis.

Impact: Our study provides key mechanistic insights into the risk of CHD by DEHP exposure during early pregnancy, and provides choline as a potentially effective intervention. DEHP suppressed the expression of key genes involved in embryonic cardiac septum development at the transcriptional level via inhibiting nuclear translocation of p65. Choline can play a role in rescuing the inhibition of DEHP on cardiogenesis genes via driving p65 translocate into the nuclear.

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