Altered microRNA expression patterns during the initiation and promotion stages of neonatal diethylstilbestrol-induced dysplasia/neoplasia in the hamster (Mesocricetus auratus) uterus

Treatment of Syrian hamsters on the day of birth with the prototypical endocrine disruptor and synthetic estrogen, diethylstilbestrol (DES), leads to 100% occurrence of uterine hyperplasia/dysplasia in adulthood, a large proportion of which progress to neoplasia (endometrial adenocarcinoma). Consist...

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Bibliographic Details
Published in:Cell biology and toxicology 2017-10, Vol.33 (5), p.483-500
Main Authors: Padmanabhan, Ramesh, Hendry, Isabel R., Knapp, Jennifer R., Shuai, Bin, Hendry, William J.
Format: Article
Language:English
Subjects:
Adenocarcinoma
Apoptosis
Biochemistry
Biological activity
Biomedical and Life Sciences
Cell Biology
Cell cycle
Diethylstilbestrol
DNA microarrays
Dysplasia
Endocrine disruptors
Endometrium
Epigenetics
Estrogens
Gene expression
Hamsters
Hyperplasia
Life Sciences
MicroRNAs
miRNA
Neonates
Newborn babies
Original Article
Pharmacology/Toxicology
Polymerase chain reaction
Promotion
Ribonucleic acid
RNA
Uterus
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Summary:Treatment of Syrian hamsters on the day of birth with the prototypical endocrine disruptor and synthetic estrogen, diethylstilbestrol (DES), leads to 100% occurrence of uterine hyperplasia/dysplasia in adulthood, a large proportion of which progress to neoplasia (endometrial adenocarcinoma). Consistent with our prior gene expression analyses at the mRNA and protein levels, we now report (based on microarray, real-time polymerase chain reaction, and in situ hybridization analyses) that progression of the neonatal DES-induced dysplasia/neoplasia phenomenon in the hamster uterus also includes a spectrum of microRNA expression alterations (at both the whole-organ and cell-specific level) that differ during the initiation (upregulated miR-21, 200a, 200b, 200c, 29a, 29b, 429, 141; downregulated miR-181a) and promotion (downregulated miR-133a) stages of the phenomenon. The biological processes targeted by those differentially expressed miRNAs include pathways in cancer and adherens junction, plus regulation of the cell cycle, apoptosis, and miRNA functions, all of which are consistent with our model system phenotype. These findings underscore the need for continued efforts to identify and assess both the classical genetic and the more recently recognized epigenetic mechanisms that truly drive this and other endocrine disruption phenomena.
ISSN:0742-2091
1573-6822
DOI:10.1007/s10565-017-9389-6