Expression of hormonal carcinogenesis genes and related regulatory microRNAs in uterus and ovaries of DDT-treated female rats

The insecticide dichlorodiphenyltrichloroethane (DDT) is a nonmutagenic xenobiotic compound able to exert estrogen-like effects resulting in activation of estrogen receptor-α (ERα) followed by changed expression of its downstream target genes. In addition, studies performed over recent years suggest...

Full description

Saved in:
Bibliographic Details
Published in:Biochemistry (Moscow) 2017-10, Vol.82 (10), p.1118-1128
Main Authors: Kalinina, T. S., Kononchuk, V. V., Gulyaeva, L. F.
Format: Article
Language:English
Subjects:
Activation
Animals
Aromatase - genetics
Aromatase - metabolism
Biochemistry
Biomedical and Life Sciences
Biomedicine
Bioorganic Chemistry
Carcinogenesis
Carcinogenesis - genetics
Carcinogens
DDT
DDT - toxicity
DEAD-box RNA Helicases - antagonists & inhibitors
DEAD-box RNA Helicases - genetics
DEAD-box RNA Helicases - metabolism
Estrogen Receptor alpha - genetics
Estrogen Receptor alpha - metabolism
Estrogen receptors
Estrogens
Female
Gene expression
Gene Expression Regulation, Neoplastic
Genes
Genetic aspects
Genetic regulation
Health aspects
Life Sciences
Microbiology
MicroRNA
MicroRNAs
MicroRNAs - genetics
miRNA
mRNA
Ovaries
Ovary - drug effects
Ovary - metabolism
Pesticides
PTEN Phosphohydrolase - antagonists & inhibitors
PTEN Phosphohydrolase - genetics
PTEN Phosphohydrolase - metabolism
PTEN protein
Rats
Rats, Wistar
Ribonuclease III - antagonists & inhibitors
Ribonuclease III - genetics
Ribonuclease III - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
Rodents
Tumor suppressor genes
Uterus
Uterus - drug effects
Uterus - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The insecticide dichlorodiphenyltrichloroethane (DDT) is a nonmutagenic xenobiotic compound able to exert estrogen-like effects resulting in activation of estrogen receptor-α (ERα) followed by changed expression of its downstream target genes. In addition, studies performed over recent years suggest that DDT may also influence expression of microRNAs. However, an impact of DDT on expression of ER, microRNAs, and related target genes has not been fully elucidated. Here, using real-time PCR, we assessed changes in expression of key genes involved in hormonal carcinogenesis as well as potentially related regulatory oncogenic/tumor suppressor microRNAs and their target genes in the uterus and ovaries of female Wistar rats during single and chronic multiple-dose DDT exposure. We found that applying DDT results in altered expression of microRNAs-221, -222, -205, -126a, and -429, their target genes ( Pten, Dicer1 ), as well as genes involved in hormonal carcinogenesis ( Esr1, Pgr, Ccnd1, Cyp19a1 ). Notably, Cyp19a1 expression seems to be also regulated by microRNAs-221, -222, and -205. The data suggest that epigenetic effects induced by DDT as a potential carcinogen may be based on at least two mechanisms: (i) activation of ERα followed by altered expression of the target genes encoding receptor Pgr and Ccnd1 as well as impaired expression of Cyp19a1 , affecting, thereby, cell hormone balance; and (ii) changed expression of microRNAs resulting in impaired expression of related target genes including reduced level of Cyp19a1 mRNA.
ISSN:0006-2979
1608-3040
DOI:10.1134/S0006297917100042