Decreased PGF may contribute to trophoblast dysfunction in fetal growth restriction

Autor: Bo Yuan, Wei-Bin Wu, Wei-Wei Cheng, Hui-Juan Zhang, Yan-Lin Wang, Yue-Ying Xu, Jiu-Ru Zhao
Rok vydání: 2017
Předmět:
Placental growth factor
Adult
endocrine system
Embryology
Placenta Diseases
Bisulfite sequencing
Biology
Cell Line
Epigenesis
Genetic
Andrology
03 medical and health sciences
0302 clinical medicine
Endocrinology
Cell Movement
Pregnancy
Placenta
medicine
Birth Weight
Humans
Promoter Regions
Genetic
Cell Proliferation
Placenta Growth Factor
Regulation of gene expression
Fetus
030219 obstetrics & reproductive medicine
Fetal Growth Retardation
Vascular Endothelial Growth Factor Receptor-1
Obstetrics and Gynecology
Trophoblast
Placentation
Gene Expression Regulation
Developmental
Cell Biology
Exons
respiratory system
DNA Methylation
Trophoblasts
medicine.anatomical_structure
Reproductive Medicine
030220 oncology & carcinogenesis
embryonic structures
DNA methylation
Quinazolines
lipids (amino acids
peptides
and proteins)
CpG Islands
Female
RNA Interference
hormones
hormone substitutes
and hormone antagonists
Zdroj: Reproduction (Cambridge, England). 154(3)
ISSN: 1741-7899
Popis: Fetal growth restriction (FGR) threatens perinatal health and is correlated with increased incidence of fetal original adult diseases. Most cases of FGR were idiopathic, which were supposed to be associated with placental abnormality. Decreased circulating placental growth factor (PGF) was recognized as an indication of placental deficiency in FGR. In this study, the epigenetic regulation of PGF in FGR placentas and the involvement of PGF in modulation of trophoblast activity were investigated. The expression level of PGF in placental tissues was determined by RT-qPCR, immunohistochemistry and ELISA. DNA methylation profile of PGF gene was analyzed by bisulfite sequencing. Trophoblastic cell lines were treated with ZM-306416, an inhibitor of PGF receptor FLT1, to observe the effect of PGF/FLT1 signaling on cell proliferation and migration. We demonstrated that PGF was downregulated in placentas from FGR pregnancies compared with normal controls. The villous expression of PGF was positively correlated with placental and fetal weight. The CpG island inside PGF promoter was hypomethylated without obvious difference in both normal and FGR placentas. However, the higher DNA methylation at another CpG island downstream exon 7 of PGF was demonstrated in FGR placentas. Additionally, we found FLT1 was expressed in trophoblast cells. Inhibition of PGF/FLT1 signaling by a selective inhibitor impaired trophoblast proliferation and migration. In conclusion, our data suggested that the PGF expression was dysregulated, and disrupted PGF/FLT1 signaling in trophoblast might contribute to placenta dysfunction in FGR. Thus, our results support the significant role of PGF in the pathogenesis of FGR.
Databáze: OpenAIRE
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