| Autor: |
Xiaoli Gong, Wei He, Wan Jin, Hongwei Ma, Gang Wang, Jiaxin Li, Yu Xiao, Yangyu Zhao, Qiong Chen, Huanhuan Guo, Jiexia Yang, Yiming Qi, Wei Dong, Meng Fu, Xiaojuan Li, Jiusi Liu, Xinghui Liu, Aihua Yin, Yi Zhang, Yuan Wei |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Genome Biology, Vol 25, Iss 1, Pp 1-46 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
1474-760X |
| DOI: |
10.1186/s13059-024-03265-z |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
Full text from SpringerLink