Placental surface area mediates the association between FGFR2 methylation in placenta and full-term low birth weight in girls

Abstract

BackgroundFibroblast growth factor receptor 2 (FGFR2) gene encodes a protein of the fibroblast growth factor receptor family. FGFR2 gene expression is associated with the regulation of implantation process of placenta which plays a vital role in fetal growth. DNA methylation is widely known as a mechanism of fetal growth. However, it is unclear whether and how DNA methylation of FGFR2 gene in the placenta is associated with full-term low birth weight. This case-control study aims to explore the links between FGFR2 methylation in placenta and full-term low birth weight and to further examine the mediation effect of placental surface area on this association.ResultsWe conducted analyses for each of the five valid CpG sites at FGFR2 in 165 mother-baby pairs (86 FT-LBW vs. 79 FT-NBW) and found that per one standard deviation increase in the DNA methylation of CpG 11 at FGFR2 was associated with 1.64-fold higher risk of full-term low birth weight (OR = 1.64, 95% CI = [1.07, 2.52]) and 0.18 standard deviation decrease in placental surface area (β = − 0.18; standard error = 0.08, p = 0.02). The mediation effect of placental surface area on the association between DNA methylation and full-term low birth weight was significant in girls (OR = 1.38, 95% CI = [1.05, 1.80]) but not in boys. The estimated mediation proportion was 48.38%.ConclusionOur findings suggested that placental surface area mediated the association between DNA methylation of FGFR2 in placenta and full-term low birth weight in a sex-specific manner. Our study supported the importance of placental epigenetic changes in placental development and fetal growth.Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0472-5) contains supplementary material, which is available to authorized users.

The angiogenic properties of human amniotic membrane stem cells are enhanced in gestational diabetes and associate with fetal adiposity

“…PAI-1 has been associated with a high pro-angiogenic activity at physiological concentrations [ 50 ], and its up- or downregulation promotes or inhibits blood vessel formation, respectively [ 51 , 52 ]. PAI-1 has been previously reported to be elevated in the serum of patients with GDM [ 43 ], and it is known to be upregulated by the pro-angiogenic placental growth factor gene [ 53 ]. In agreement with these data, we observed that TM5275, a PAI-1 selective pharmacological inhibitor, substantially attenuated the angiogenic capacity of GDM-hAMSCs.…”

Comparison of DNA methylation profiles associated with spontaneous preterm birth in placenta and cord blood

“…Maternal socio-demographic characteristics, medical and reproductive history were collected via clinic interviews after delivery, and pregnancy information (e.g., pregnancy complications, offspring biometric measures at birth) were extracted from medical records by trained study staff, the questionnaire used in the interviews had been employed in our previous works [35–37]. Details of delivery were measured and recorded by midwives, including birth weight (measured to the nearest 5 g), birth length, head circumference, as well as placental diameters and thickness.…”

A Pancancer Analysis of the Expression Landscape and Clinical Relevance of Fibroblast Growth Factor Receptor 2 in Human Cancers

“…The correlation analysis showed that there was a positive correlation between FGFR2 CNVs and mRNA expression in pancancer (r = 0.1578, p < 0.0001) (Supplementary Figure 2B). In addition, some other factors might also affect the expression of FGFR2, such as methylation (43).…”