Prenatal Exposure to Lipopolysaccharide Alters Renal DNA Methyltransferase Expression in Rat Offspring

Jing Wang; Jinghong Cui; Rui Chen; Youcai Deng; Xi Liao; Yanling Wei; Xiaohui Li; Min Su; Jianhua Yu; Ping Yi

doi:10.1371/journal.pone.0169206

Prenatal Exposure to Lipopolysaccharide Alters Renal DNA Methyltransferase Expression in Rat Offspring

PLoS One. 2017 Jan 19;12(1):e0169206. doi: 10.1371/journal.pone.0169206. eCollection 2017.

Authors

Jing Wang¹, Jinghong Cui¹, Rui Chen², Youcai Deng², Xi Liao¹, Yanling Wei³, Xiaohui Li², Min Su², Jianhua Yu^{1

4}, Ping Yi¹

Affiliations

¹ Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
² Institute of Materia Medica, College of Pharmacy, Third Military Medical University, Chongqing, China.
³ Department of Gastroenterology, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
⁴ The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, United States of America.

Abstract

Prenatal exposure to inflammation results in hypertension during adulthood but the mechanisms are not well understood. Maternal exposure to lipopolysaccharide (LPS) alters interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels in the fetal environment. As reported in many recent studies, IL-6 regulates DNA methyltransferases (DNMTs) through the transcription factor friend leukemia virus integration 1 (Fli-1). The present study explores the role of intrarenal DNMTs during development of hypertension induced by prenatal exposure to LPS. Pregnant rats were randomly divided into four treatment groups: control, LPS, pyrrolidine dithiocarbamate (PDTC, a NF-κB inhibitor), and the combination of LPS and PDTC. Expression of IL-6, Fli-1, TNF-α, DNMT1 and DNMT3B was significantly increased in the offspring of LPS-treated rats. Global DNA methylation level of renal cortex also increased dramatically in rat offspring of the LPS group. Prenatal PDTC administration reversed the increases in gene expression and global DNA methylation level. These findings suggest that prenatal exposure to LPS may result in changes of intrarenal DNMTs through the IL-6/Fli-1 pathway and TNF-α, which probably involves hypertension in offspring due to maternal exposure to inflammation.

MeSH terms

Animals
DNA (Cytosine-5-)-Methyltransferase 1
DNA (Cytosine-5-)-Methyltransferases / genetics
DNA (Cytosine-5-)-Methyltransferases / metabolism*
DNA Methylation / drug effects
DNA Methyltransferase 3A
DNA Methyltransferase 3B
Female
Hypertension / etiology
Hypertension / genetics
Hypertension / metabolism
Inflammation / etiology
Inflammation / genetics
Inflammation / metabolism
Interleukin-6 / genetics
Interleukin-6 / metabolism
Kidney / drug effects*
Kidney / metabolism*
Lipopolysaccharides / administration & dosage
Lipopolysaccharides / toxicity*
Pregnancy
Prenatal Exposure Delayed Effects / genetics
Prenatal Exposure Delayed Effects / metabolism*
Proto-Oncogene Protein c-fli-1 / genetics
Proto-Oncogene Protein c-fli-1 / metabolism
RNA, Messenger / genetics
RNA, Messenger / metabolism
Rats
Rats, Sprague-Dawley
Signal Transduction / drug effects
Tumor Necrosis Factor-alpha / metabolism

Substances

Interleukin-6
Lipopolysaccharides
Proto-Oncogene Protein c-fli-1
RNA, Messenger
Tumor Necrosis Factor-alpha
DNA (Cytosine-5-)-Methyltransferase 1
DNA (Cytosine-5-)-Methyltransferases
DNA Methyltransferase 3A
Dnmt1 protein, rat

Grants and funding

This work was supported by the National Natural Science Foundation of China, Grant numbers: 81170580 (http://www.nsfc.gov.cn/) to PY. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.