RGD Reference Report - Increased m6A RNA modification is related to the inhibition of the Nrf2-mediated antioxidant response in di-(2-ethylhexyl) phthalate-induced prepubertal testicular injury. - Rat Genome Database

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Increased m6A RNA modification is related to the inhibition of the Nrf2-mediated antioxidant response in di-(2-ethylhexyl) phthalate-induced prepubertal testicular injury.

Authors: Zhao, Tian-Xin  Wang, Jun-Ke  Shen, Lian-Ju  Long, Chun-Lan  Liu, Bin  Wei, Yi  Han, Lin-Dong  Wei, Yue-Xin  Wu, Sheng-De  Wei, Guang-Hui 
Citation: Zhao TX, etal., Environ Pollut. 2020 Apr;259:113911. doi: 10.1016/j.envpol.2020.113911. Epub 2020 Jan 6.
RGD ID: 329951021
Pubmed: PMID:31923814   (View Abstract at PubMed)
DOI: DOI:10.1016/j.envpol.2020.113911   (Journal Full-text)

Di-(2-ethylhexyl) phthalate (DEHP) is a common environmental endocrine disrupting chemical that may induce male reproductive disorders. Exposure to DEHP at a prepubertal stage could lead to prepubertal testicular injury, but the underlying mechanisms remain unclear. In this study, we exposed Sprague-Dawley rats to 0, 250, and 500 mg DEHP per kg body weight per day at the prepuberty stage from postnatal day 22 (PND 22) to PND 35 by oral gavage. Testicular injury and oxidative stress were evaluated, and the levels of 6-methyladenosine (m6A) modification and expression of modulator genes for RNA methylation were measured in testes. Furthermore, m6A modification of the important antioxidant transcription factor Nrf2 was analyzed using methylated RNA immunoprecipitation qPCR. Our results show that DEHP worsened testicular histology, decreased testosterone concentrations, downregulated expression of spermatogenesis inducers, enhanced oxidative stress, inhibited the Nrf2-mediated antioxidant pathway, and increased apoptosis in testes. Additionally, DEHP increased global levels of m6A RNA modification and altered the expression of two important RNA methylation modulator genes, FTO and YTHDC2. Moreover, m6A modification of Nrf2 mRNA increased upon DEHP exposure. Overall, these findings link oxidative stress imbalance with epigenetic effects of DEHP toxicity and provide insight into the testicular toxicity of DEHP from the new perspective of m6A modification.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FTOHumanTesticular Injury  ISOFto (Rattus norvegicus)mRNA:decreased expression:testisRGD 
FtoRatTesticular Injury  IEP mRNA:decreased expression:testisRGD 
FtoMouseTesticular Injury  ISOFto (Rattus norvegicus)mRNA:decreased expression:testisRGD 

Objects Annotated

Genes (Rattus norvegicus)
Fto  (FTO, alpha-ketoglutarate dependent dioxygenase)

Genes (Mus musculus)
Fto  (FTO alpha-ketoglutarate dependent dioxygenase)

Genes (Homo sapiens)
FTO  (FTO alpha-ketoglutarate dependent dioxygenase)


Additional Information