Altered placental immune cell composition and gene expression with isolated fetal spina bifida

Abstract

AbstractProblemMaternal B vitamin deficiency increases the risk of fetal spina bifida (SB) and placental maldevelopment. It is unclear whether placental processes involving folate are altered in fetuses with SB in a contemporary cohort. We hypothesised that fetal SB would associate with reduced expression of key folate transporters (folate receptor-α [FRα], proton coupled folate receptor [PCFT], and reduced folate carrier [RFC]), and an increase in Hofbauer cell (HBC) abundance and folate receptor-β(FRβ)expression by HBCs.Method of StudyFRα, PCFT, and RFC protein localisation and expression (immunohistochemistry) and HBC phenotypes (RNAin situhybridization) were assessed in placentae from fetuses with SB (cases; n=12) and with no congenital anomalies (controls; n=22).ResultsCases (vs. gestational age [GA]-matched controls) had a higher proportion of placental villous cells that were HBCs (6.9% vs. 2.4%, p=0.0001) and higher averageFRβexpression by HBCs (3.2 mRNA molecules per HBC vs. 2.3, p=0.03). HBCs in cases were largely polarised to a regulatory (M2) phenotype (median 92.1% of HBCs). In sex-stratified analyses, male, but not female, cases had higher HBC levels andFRβexpression by HBCs than GA-matched controls. There were no differences between groups in the total percent of syncytium and stromal cells that were positive for FRα, PCFT, or RFC protein immunolabelling.ConclusionsHBC abundance andFRβexpression by HBCs are increased in placentae of fetuses with isolated SB, suggesting immune-mediated dysregulation in placental development and function, and could contribute to SB-associated comorbidities, such as poor fetal growth.