Problem: Maternal 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 Study: FRα, PCFT, and RFC protein localisation and expression (immunohistochemistry) and HBC phenotypes (RNA in situ hybridization) were assessed in placentae from fetuses with SB (cases; n=12) and with no congenital anomalies (controls; n=22). Results: Cases (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 average FRβ expression by HBCs (3.2 mRNA molecules per HBC vs. 2.3, p=0.03). HBCs in cases were largely polarised to a regulatory phenotype (median 92.1% of HBCs). In sex-stratified analyses, male, but not female, cases had higher HBC levels and FRβ expression 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. Conclusions: HBC abundance and FRβ expression 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.

中文翻译：

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分离胎儿脊柱裂改变胎盘免疫细胞组成和基因表达

问题：母亲 B 族维生素缺乏会增加胎儿脊柱裂 (SB) 和胎盘发育不良的风险。目前尚不清楚在当代队列中患有 SB 的胎儿中涉及叶酸的胎盘过程是否发生改变。我们假设胎儿​​ SB 与关键叶酸转运蛋白（叶酸受体-α [FRα]、质子偶联叶酸受体 [PCFT] 和减少叶酸载体 [RFC]）表达减少以及霍夫鲍尔细胞 (HBC) 丰度增加有关以及 HBC 的叶酸受体-β (FRβ) 表达。研究方法：对患有 SB 的胎儿（病例；n=12）和无先天性异常（对照；n =22）。结果：病例（与胎龄 [GA] 匹配的对照相比）具有较高比例的 HBC 胎盘绒毛细胞（6.9% vs. 2.4%，p=0.0001），并且 HBC 的平均 FRβ 表达较高（每个 3.2 个 mRNA 分子）。 HBC 与 2.3，p=0.03）。病例中的 HBC 在很大程度上极化为监管表型（HBC 的中位数为 92.1%）。在性别分层分析中，男性而非女性病例的 HBC 水平和 HBC 的 FRβ 表达高于 GA 匹配的对照。FRα、PCFT 或 RFC 蛋白免疫标记呈阳性的合胞体和基质细胞的总百分比在各组之间没有差异。结论：在孤立性 SB 胎儿的胎盘中，HBC 丰度和 HBC 的 FRβ 表达增加，表明胎盘发育和功能中免疫介导的失调，并可能导致 SB 相关的合并症，例如胎儿生长不良。