BACKGROUND Elongation factor Tu GTP binding domain containing 2 (EFTUD2) is an alternative splicing factor that modulates cell differentiation and activation processes. EFTUD2 is known to modulate immune responses and mutation of the EFTUD2-gene lead to fetal malformation. Little is known about its expression and role in normal and disturbed first trimester pregnancy. PATIENTS AND METHODS We investigated the expression of EFTUD2 in placental tissue obtained from patients with normal (n = 14), spontaneous miscarriage (n = 15) and molar (n = 14) pregnancy by immunohistochemistry. The expression of EFTUD2 was correlated on the protein level with known immune modulatory proteins like pregnancy zone protein (PZP) and in addition with human chorionic gonadotropin (hCG). Furthermore, we analysed the EFTUD2 and PZP expression in vitro after stimulation of the chorioncarcinoma cell line JEG-3 with hCG. RESULTS EFTUD2 is significantly upregulated in the syncytiotrophoblast of spontaneous miscarriage (p = 0.003) and molar pregnancy (p = 0.003) compared to week of gestation-adjusted normal first trimester placentas. PZP is negatively correlated (p = 0.021) to EFTUD2 in the syncytiotrophoblast and is therefore significantly downregulated in miscarriage (p = 0.028) and mole pregnancy (p = 0.006). In addition, hCG is positively correlated to EFTUD2 in mole pregnancy. The addition of hCG to chorioncarcinoma cell lines JEG-3 in vitro stimulated EFTUD2 expression in these cells (p = 0.027). CONCLUSION Regulation of alternative splicing seems crucial for a successful ongoing pregnancy. The up-regulated elongation factor EFTUD2 may have a critical role in miscarriage.

中文翻译：

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剪接体蛋白 EFTUD2 在自然流产和葡萄胎的滋养细胞中上调。

背景延伸因子Tu GTP结合域包含2 (EFTUD2)是调节细胞分化和活化过程的替代剪接因子。已知 EFTUD2 可调节免疫反应，并且 EFTUD2 基因的突变会导致胎儿畸形。关于它在正常和不安的头三个月妊娠中的表达和作用知之甚少。患者和方法 我们通过免疫组织化学研究了从正常 (n = 14)、自然流产 (n = 15) 和磨牙 (n = 14) 妊娠患者获得的胎盘组织中 EFTUD2 的表达。EFTUD2 的表达在蛋白质水平上与已知的免疫调节蛋白如妊娠区蛋白 (PZP) 以及人绒毛膜促性腺激素 (hCG) 相关。此外，我们在体外分析了用 hCG 刺激绒毛膜癌细胞系 JEG-3 后 EFTUD2 和 PZP 的表达。结果 EFTUD2 在自然流产 (p = 0.003) 和葡萄胎 (p = 0.003) 的合体滋养层细胞中显着上调，与经妊娠调整的正常妊娠早期胎盘的周数相比。PZP 与合体滋养层中的 EFTUD2 呈负相关 (p = 0.021)，因此在流产 (p = 0.028) 和葡萄胎妊娠 (p = 0.006) 中显着下调。此外，在葡萄胎妊娠中，hCG 与 EFTUD2 呈正相关。将 hCG 添加到绒毛膜癌细胞系 JEG-3 体外刺激了这些细胞中的 EFTUD2 表达（p = 0.027）。结论 选择性剪接的调控对于成功的持续妊娠似乎至关重要。