| RRC ID |
74311
|
| 著者 |
Nagif Alata Jimenez, Mauricio Castellano, Emilio M. Santillan, Konstantinos Boulias, Agustín Boan, Luisa F. Arias Padilla, Juan I. Fernandino, Eric L. Greer, Juan P. Tosar, Luisa Cochella, Pablo H. Strobl-Mazzulla
|
| タイトル |
Paternal methotrexate exposure affects sperm small RNA content and causes craniofacial defects in the offspring
|
| ジャーナル |
Nature Communications
|
| Abstract |
Folate is an essential vitamin for vertebrate embryo development. Methotrexate (MTX) is a folate antagonist that is widely prescribed for autoimmune diseases, blood and solid organ malignancies, and dermatologic diseases. Although it is highly contraindicated for pregnant women, because it is associated with an increased risk of multiple birth defects, the effect of paternal MTX exposure on their offspring has been largely unexplored. Here, we found MTX treatment of adult medaka male fish (Oryzias latipes) causes cranial cartilage defects in their offspring. Small non-coding RNA (sncRNAs) sequencing in the sperm of MTX treated males identify differential expression of a subset of tRNAs, with higher abundance for specific 5′ tRNA halves. Sperm RNA methylation analysis on MTX treated males shows that m5C is the most abundant and differential modification found in RNAs ranging in size from 50 to 90 nucleotides, predominantly tRNAs, and that it correlates with greater testicular Dnmt2 methyltransferase expression. Injection of sperm small RNA fractions from MTX-treated males into normal fertilized eggs generated cranial cartilage defects in the offspring. Overall, our data suggest that paternal MTX exposure alters sperm sncRNAs expression and modifications that may contribute to developmental defects in their offspring.
|
| 巻・号 |
14
|
| 公開日 |
2023-3-23
|
| DOI |
10.1038/s41467-023-37427-7
|
| PMID |
36959185
|
| PMC |
PMC10036556
|
| MeSH |
Animals
Female
Folic Acid / metabolism
Humans
Male
Methotrexate* / adverse effects
Methotrexate* / metabolism
Pregnancy
RNA, Small Untranslated* / genetics
RNA, Transfer / genetics
RNA, Transfer / metabolism
Semen
Spermatozoa / metabolism
|
| IF |
12.121
|
| リソース情報 |
| メダカ |
hi-medaka (MT835) |
