title: Prenatal Exposure to Lipopolysaccharide Alters Renal DNA Methyltransferase Expression in Rat Offspring.
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.
authors.affiliation: Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jinghong
authors.initials: J
authors.lastname: Cui
authors.affiliation: Institute of Materia Medica, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.affiliation: Institute of Materia Medica, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Youcai
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Liao
authors.affiliation: Department of Gastroenterology, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Institute of Materia Medica, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Materia Medica, College of Pharmacy, Third Military Medical University, Chongqing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Su
authors.affiliation: Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.|The Ohio State University Comprehensive Cancer Center, Columbus, Ohio, United States of America.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Obstetrics and Gynecology, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yi
mesh_terms: D000818:Animals; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation / Q000187:drug effects; D000090205:DNA Methyltransferase 3A; D005260:Female; D006973:Hypertension / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics / Q000378:metabolism*; D051789:Proto-Oncogene Protein c-fli-1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097584:DNA Methyltransferase 3B
chemical_list: D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D015850:Interleukin-6; D008070:Lipopolysaccharides; D051789:Proto-Oncogene Protein c-fli-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000097584:DNA Methyltransferase 3B; C000619382:Dnmt1 protein, rat