Prenatal nicotinic exposure suppresses fetal adrenal steroidogenesis via steroidogenic factor 1 (SF-1) deacetylation.
This study aimed to investigate the suppressive effect of nicotine on fetal adrenal steroidogenesis and to explore the potential role of epigenetic modification of steroidogenic factor-1 (SF-1) transcriptional activity in this process. Nicotine was intragastrically administered to pregnant rats and NCI-H295A cells were treated with nicotine or trichostatin A (TSA). The pathomorphology of fetal adrenals, steroid hormone levels, the expression of SF-1 and its target genes, and histone deacetylase (HDAC) mRNA were analyzed. Histone modification and DNA methylation of the SF-1 promoter region were assessed using chromatin immunoprecipitation (ChIP) and bisulfite sequencing PCR. The interaction between SF1 and its target genes was observed. Prenatal nicotinic exposure decreased fetal body weight, increased the IUGR rate and caused detrimental changes in fetal adrenal. In addition, the levels of corticosterone, the expression of SF-1 and its target genes were decreased while HDAC2 expression was enhanced. Nicotine treatment decreased histone H3K9 and H3K14 acetylation levels while there was no effect on the methylation frequency on the SF-1 promoter region. Furthermore, in nicotine-treated NCI-H295A cells, lower levels of steroidogenic synthesis, lower expression of SF-1 and its target genes were observed while the expression of HDACs was enhanced. The interaction between SF1 and StAR decreased with nicotine treatment. Nicotine treatment decreased histone H3K9 and H3K14 acetylation levels, and addition of TSA reversed the inhibition of nicotine-mediated SF-1 and its partial target genes. Thus, nicotine-mediated reduction of SF-1 expression resulted in an inhibitory effect on the expression of its target genes and steroid production via histone deacetylation.
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, China.
You-E
YE
Yan
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, China; Department of Pharmacology, Medical School of Yangtze University, Jingzhou 434000, China.
Lian
L
Liu
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, China.
Jian-Fei
JF
Wang
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, China.
Fang
F
Liu
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, China.
Xiao-Hai
XH
Li
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, China.
Hai-Quan
HQ
Qin
Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, China; Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071, China. Electronic address: wanghui19@whu.edu.cn.
Hui
H
Wang
D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D057890:Epigenomics; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D005317:Fetal Growth Retardation / Q000139:chemically induced; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D018811:Maternal Exposure; D009538:Nicotine / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D054339:Steroidogenic Factor 1 / Q000235:genetics / Q000378:metabolism*
D054339:Steroidogenic Factor 1; C515060:steroidogenic factor 1, rat; D009538:Nicotine
Histone deacetylation; Nicotine; Steroidogenesis; Steroidogenic factor-1