Differential Placental Gene Expression in Term Pregnancies Affected by Fetal Growth Restriction and Macrosomia

Abstract

Introduction: Extremes of fetal growth are associated with increased perinatal mortality and morbidity and a higher prevalence of cardiovascular disease, obesity and diabetes in later life. We aimed to identify changes in placental gene expression in pregnancies with evidence of growth dysfunction and candidate genes that may be used to identify abnormal patterns of growth prior to delivery. Methods: Growth-restricted (n = 4), macrosomic (n = 6) and normal term (n = 5) placentas were selected from a banked series (n = 200) collected immediately after caesarean section. RNA was extracted prior to microarray analysis using Affymetrix HG-U219 arrays to determine variation in gene expression. Genes of interest were confirmed using qRT-PCR. Results: 338 genes in the growth-restricted and 41 genes in the macrosomic group were identified to be significantly dysregulated (>2-fold change; p < 0.05). CPXM2 and CLDN1 were upregulated and TXNDC5 and LRP2 downregulated in fetal growth restriction. In macrosomia, PHLDB2 and CLDN1 were upregulated and LEP and GCH1 were downregulated. Discussion: Dysfunctional growth is associated with differential placental gene expression and affects genes with a whole spectrum of developmental and cellular functions. Better elucidation of these pathways may allow the development of biomarkers to identify growth abnormalities and effective prenatal intervention.

Placental microRNA Expression Associates with Birthweight through Control of Adipokines: Results from Two Independent Cohorts

“…Both of these hormones have been linked to gestational diseases like preeclampsia [54][55][56][57][58] , gestational diabetes [58][59][60][61] and fetal outcomes like intrauterine growth restriction 46,58,59,[62][63][64][65][66] . While earlier work did find positive associations between placental leptin expression and birthweight 59,60,67 , several studies since have found a negative correlation -which is in line with our findings 63,65,[68][69][70][71][72] .…”

Placental genetic variations in vitamin D metabolism and birthweight

“…This increase implied that cubilin may be important in placental functions, related to maternal-fetal nutrient transfer [28]. Gene expression analysis by Sabri et al revealed that LRP2 was downregulated in four placentas from fetal growth restricted pregnancies but not among 11 placentas from macrosomic or normal-term pregnancies [29]. LRP2 (low density lipoprotein-related protein 2) or megalin, is a multi-ligand endocytic receptor.…”

Identification of novel biomarker candidates for immunohistochemical diagnosis to distinguish low‐grade chondrosarcoma from enchondroma

“…CPXM2 is a member of the metallocarboxypeptidase gene family and identified from its homology with carboxypeptidase E . It is upregulated in fetal growth restriction . All six were identified with multiple peptides and involved in cancer.…”