Disruption of maternal vascular remodeling by a fetal endoretrovirus-derived gene in preeclampsia.
Genome Biol
; 25(1): 117, 2024 05 07.
Article
em En
| MEDLINE
| ID: mdl-38715110
ABSTRACT
BACKGROUND:
Preeclampsia, one of the most lethal pregnancy-related diseases, is associated with the disruption of uterine spiral artery remodeling during placentation. However, the early molecular events leading to preeclampsia remain unknown.RESULTS:
By analyzing placentas from preeclampsia, non-preeclampsia, and twin pregnancies with selective intrauterine growth restriction, we show that the pathogenesis of preeclampsia is attributed to immature trophoblast and maldeveloped endothelial cells. Delayed epigenetic reprogramming during early extraembryonic tissue development leads to generation of excessive immature trophoblast cells. We find reduction of de novo DNA methylation in these trophoblast cells results in selective overexpression of maternally imprinted genes, including the endoretrovirus-derived gene PEG10 (paternally expressed gene 10). PEG10 forms virus-like particles, which are transferred from the trophoblast to the closely proximate endothelial cells. In normal pregnancy, only a low amount of PEG10 is transferred to maternal cells; however, in preeclampsia, excessive PEG10 disrupts maternal vascular development by inhibiting TGF-beta signaling.CONCLUSIONS:
Our study reveals the intricate epigenetic mechanisms that regulate trans-generational genetic conflict and ultimately ensure proper maternal-fetal interface formation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pré-Eclâmpsia
/
Trofoblastos
/
Remodelação Vascular
Limite:
Female
/
Humans
/
Pregnancy
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article