Halal Research Center of IRI, FDA, Tehran, Iran.
Department of Medical Immunology and Allergy, Student Research Committee, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Iran Biomed J. 2020 Sep;24(5):295-305. doi: 10.29252/ibj.24.5.290. Epub 2020 Feb 23.
Vitamin D insufficiency and deficiency can be associated with adverse effects on fetus and pregnancy outcomes. This study aimed at evaluating the effect of 1,25VitD3 on specific transcription factor and markers of Tregs and T helper 17 (Th17) cells in peripheral blood mononuclear cells (PBMCs) of women with unexplained recurrent pregnancy loss (URPL) as a case group and PBMCs of healthy women as a control group.
Samples from 20 non-pregnant patients with a history of URPL were compared to 20 normal non-pregnant women. PBMCs were divided into three wells for each subject in the presence of 1,25VitD3 (50 nM, for 16 hours), phytohemagglutinin (10 µM; positive control), and without any treatment (negative control). By Real-time PCR (Taqman assay), specific transcription factors of Tregs and Th17 cells, forkhead box P3 (FOXP3), retinoic acid-related orphan receptor γt (ROR-γt), glucocorticoid-induced tumor necrosis factor receptor-related (GITR), and CTLA-4 mRNA expressions in two groups were measured.
FOXP3/ROR-γt mRNA expression in PBMCs decreased significantly in women experiencing URPL compared to the control group (p = 0.0001). Although 1,25VitD3 (50 nM) increased FOXP3 gene expression (p = 0.0001), it did not significantly affect ROR-γt gene expression. Besides, 1,25VitD3 treatment significantly increased FOXP3/ROR-γt mRNA expression from baseline in PBMCs of the fetal loss group compared to that of the control group (p = 0.01). The 1,25VitD3 also increased GITR gene expression (p = 0.017) in PBMCs of URPL women compared to the controls.
Vitamin D deficiency may be a contributor to recurrent pregnancy loss and suggests that the supplementation of women with Vitamin D pre-pregnancy may be protective against URPL via affecting Tregs signature genes, FOXP3 and GITR.
维生素 D 不足和缺乏与胎儿和妊娠结局不良有关。本研究旨在评估 1,25VitD3 对不明原因复发性妊娠丢失（URPL）患者外周血单个核细胞（PBMC）中特定转录因子和 T 调节细胞（Tregs）和 T 辅助 17（Th17）细胞标志物的影响，作为病例组，并将 PBMC 与健康女性作为对照组进行比较。
将 20 名非妊娠 URPL 病史患者的样本与 20 名正常非妊娠女性进行比较。将 PBMC 分为三个孔，每个孔都有 1,25VitD3（50 nM，16 小时）、植物血凝素（10 μM；阳性对照）和无任何治疗（阴性对照）。通过实时 PCR（Taqman 测定），测量两组中 Tregs 和 Th17 细胞的特定转录因子叉头框 P3（FOXP3）、维甲酸相关孤儿受体 γt（ROR-γt）、糖皮质激素诱导的肿瘤坏死因子受体相关（GITR）和 CTLA-4 mRNA 的表达。
与对照组相比，URPL 女性 PBMC 中的 FOXP3/ROR-γt mRNA 表达明显降低（p = 0.0001）。尽管 1,25VitD3（50 nM）增加了 FOXP3 基因的表达（p = 0.0001），但它并没有显著影响 ROR-γt 基因的表达。此外，1,25VitD3 治疗可显著增加胎儿丢失组 PBMC 中 FOXP3/ROR-γt mRNA 表达，与对照组相比差异有统计学意义（p = 0.01）。1,25VitD3 还增加了 URPL 女性 PBMC 中的 GITR 基因表达（p = 0.017），与对照组相比差异有统计学意义。
维生素 D 缺乏可能是复发性妊娠丢失的一个原因，并表明女性在妊娠前补充维生素 D 可能通过影响 Tregs 特征基因 FOXP3 和 GITR 来预防 URPL。
