Issue 3, 2020

HNF4a transcription is a target of trichloroethylene toxicity in the embryonic mouse heart

Abstract

In exploration of congenital heart defects produced by TCE, Hepatocyte Nuclear Factor 4 alpha (HNF4a) transcriptional activity was identified as a central component. TCE exposure altered gene transcription in the chick heart in a non-monotonic pattern where only low dose exposure inhibited transcription by HNF4a. As the chick embryo is non-placental, we examine here HNF4a as a target of TCE in developing mouse embryos. Benfluorex and Bi6015, published agonist and antagonist, respectively, of HNF4a were compared to low dose TCE exposure. Pregnant mice were exposed to 10 ppb (76 nM) TCE, 5 μM Benfluorex, 5 μM Bi6015, or a combination of Bi6015 and TCE in drinking water. Litters (E12) were collected during a sensitive window in heart development. Embryonic hearts were collected, pooled for extraction of RNA and marker expression was examined by quantitative PCR. Multiple markers, previously identified as sensitive to TCE exposure in chicks or as published targets of HNF4a transcription were significantly affected by Benfluorex, Bi6015 and TCE. Activity of TCE and both HNF4a-specific reagents on transcription argues that HNF4a is a component of TCE cardiotoxicity and likely a proximal target of low dose exposure during development. The effectiveness of these reagents after delivery in maternal drinking water suggests that neither maternal metabolism, nor placental transport is protective of exposure.

Graphical abstract: HNF4a transcription is a target of trichloroethylene toxicity in the embryonic mouse heart

Article information

Article type
Paper
Submitted
20 Kax 2019
Accepted
26 Nah 2020
First published
05 Cig 2020

Environ. Sci.: Processes Impacts, 2020,22, 824-832

HNF4a transcription is a target of trichloroethylene toxicity in the embryonic mouse heart

S. Chen, A. Lencinas, M. Nunez, O. I. Selmin and R. B. Runyan, Environ. Sci.: Processes Impacts, 2020, 22, 824 DOI: 10.1039/C9EM00597H

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements