MicroRNAs expression in the ethylene glycol monomethyl ether-induced testicular lesion.
Ethylene glycol monomethyl ether (EGME) induces testicular lesion in rats and human. To investigate miRNAs expression in EGME testicular lesion, miRNA array assay and real-time RT-PCR analysis were conducted by using testis in rats treated with 50 and 2,000 mg/kg EGME for 6 and 24 hr. The expression of corresponding target gene for miRNAs was also examined. At 50 mg/kg, there were no changes in the gene expression and histopathological examination. At 2,000 mg/kg, slight decrease of phacytene spermatocytes with cell shrinkage and nucleus pyknosis at 6 hr and remarkable decrease (or cell death) of phacytene spermatocytes with Sertoli cell vacuolation at 24 hr were observed. After 24 hr, miR-449a and miR-92a decreased obviously and, miR-320, miR-134 and miR-188 increased, while only miR-760-5p increased after 6 hr. Above these miRNAs are reported to have an important role for spermatogenesis. The gene expression of Bcl-2, target for miR-449a, increased and therefore it is considered anti-apoptotic reaction has started in this stage. The expression of high mobility group AT-hook 2 (target of miR-92a) which regulates histone structure, was increased. Furthermore, histone deacethylase 4, targets for miR-320, was also affected. Above prohibiting apoptosis or activating epigenetic genes might be protective reaction to spermatocytes death under the miRNAs regulation in EGME testicular lesion.
Biochemical Toxicology, School of pharmaceutical sciences, Showa University, Tokyo, Japan. tamio.fukushima@shionogi.co.jp
Tamio
T
Fukushima
Kenji
K
Taki
Ryota
R
Ise
Ikuo
I
Horii
Takemi
T
Yoshida
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D044127:Epigenesis, Genetic / Q000187:drug effects / Q000235:genetics; D005026:Ethylene Glycols / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D060888:Real-Time Polymerase Chain Reaction; D012708:Sertoli Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013091:Spermatogenesis / Q000187:drug effects / Q000235:genetics; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D018675:Toxicity Tests
D005026:Ethylene Glycols; D035683:MicroRNAs; C005398:phenoxyethanol