Pregnancy Is Associated with Impaired Transcription of Human Endogenous Retroviruses and of TRIM28 and SETDB1, Particularly in Mothers Affected by Multiple Sclerosis

Accumulating evidence highlights the pathogenetic role of human endogenous retroviruses (HERVs) in eliciting and maintaining multiple sclerosis (MS). Epigenetic mechanisms, such as those regulated by TRIM 28 and SETDB1, are implicated in HERV activation and in neuroinflammatory disorders, including...

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Vydáno v:Viruses Ročník 15; číslo 3; s. 710
Hlavní autoři: Tovo, Pier-Angelo, Marozio, Luca, Abbona, Giancarlo, Calvi, Cristina, Frezet, Federica, Gambarino, Stefano, Dini, Maddalena, Benedetto, Chiara, Galliano, Ilaria, Bergallo, Massimiliano
Médium: Journal Article
Jazyk:angličtina
Vydáno: Switzerland MDPI AG 09.03.2023
MDPI
Témata:
Autoimmune diseases
blood
Care and treatment
Chorion
Cord blood
Cytokines
Decidua
Diagnosis
Disease
DNA methylation
Endogenous Retroviruses - genetics
Epigenesis, Genetic
Epigenetics
Female
Genes, env
Genomes
Gestation
Health aspects
Histone-Lysine N-Methyltransferase - genetics
Histone-Lysine N-Methyltransferase - metabolism
human endogenous retroviruses
Humans
Infant, Newborn
Inflammation
Medical innovations
Mothers
Multiple Sclerosis
Neonates
pathogenesis
Peripheral blood
Placenta
polymerase chain reaction
Pregnancy
Pregnancy Complications
Pregnant women
Proteins
Retroviridae
RNA, Messenger
sclerosis
SETDB1
Syncytin
Therapeutic applications
therapeutics
transcription (genetics)
TRIM28
Tripartite Motif-Containing Protein 28 - genetics
Tripartite Motif-Containing Protein 28 - metabolism
Womens health
Italy
United States > US
SETDB1
TRIM28
human endogenous retroviruses
multiple sclerosis
pregnancy
ISSN:1999-4915, 1999-4915
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Shrnutí:Accumulating evidence highlights the pathogenetic role of human endogenous retroviruses (HERVs) in eliciting and maintaining multiple sclerosis (MS). Epigenetic mechanisms, such as those regulated by TRIM 28 and SETDB1, are implicated in HERV activation and in neuroinflammatory disorders, including MS. Pregnancy markedly improves the course of MS, but no study explored the expressions of HERVs and of TRIM28 and SETDB1 during gestation. Using a polymerase chain reaction real-time Taqman amplification assay, we assessed and compared the transcriptional levels of pol genes of HERV-H, HERV-K, HERV-W; of env genes of Syncytin (SYN)1, SYN2, and multiple sclerosis associated retrovirus (MSRV); and of TRIM28 and SETDB1 in peripheral blood and placenta from 20 mothers affected by MS; from 27 healthy mothers, in cord blood from their neonates; and in blood from healthy women of child-bearing age. The HERV mRNA levels were significantly lower in pregnant than in nonpregnant women. Expressions of all HERVs were downregulated in the chorion and in the decidua basalis of MS mothers compared to healthy mothers. The former also showed lower mRNA levels of HERV-K-pol and of SYN1, SYN2, and MSRV in peripheral blood. Significantly lower expressions of TRIM28 and SETDB1 also emerged in pregnant vs. nonpregnant women and in blood, chorion, and decidua of mothers with MS vs. healthy mothers. In contrast, HERV and TRIM28/SETDB1 expressions were comparable between their neonates. These results show that gestation is characterized by impaired expressions of HERVs and TRIM28/SETDB1, particularly in mothers with MS. Given the beneficial effects of pregnancy on MS and the wealth of data suggesting the putative contribution of HERVs and epigenetic processes in the pathogenesis of the disease, our findings may further support innovative therapeutic interventions to block HERV activation and to control aberrant epigenetic pathways in MS-affected patients.
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SourceType-Scholarly Journals-1
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ISSN:1999-4915
1999-4915
DOI:10.3390/v15030710