Evaluation of 1,25 vitamin D3 (1,25 (OH)2D3) effects on FOXP3 , ROR- γt, GITR and CTLA-4 gene expression in the PBMCs of Vitamin D deficient women with Unexplained Recurrent Pregnancy Loss (URPL)

Background and Aim : Vitamin D insufficiency and deficiency can be associated with adverse effects onfetus and pregnancy outcomes. The aim of this study was to evaluate the effect of 1,25VitD3 on specifictranscription factor and markers of regulatory T cells and Th17 cells in women with unexplained recurrentpregnancy loss (URPL) as a case group and healthy women as a control group.Methods : Samples from 20 non-pregnant patients with a history unexplained recurrent pregnancy losswere compared to 20 normal non-pregnant women. Peripheral blood mononuclear cells (PBMCs) weredivided in to 3 wells for each subject; in the presence of 1,25 vitD3 (50 nM, for 16 hours), PHA (positivecontrol) (10μM) and without any treatment (negative control).By Real time PCR ( Taqman assay) specifictranscription factors of regulatory T cells and Th17 cells; FOXP3 , ROR- γt ,GITR and CTLA-4 mRNAexpressions in two groups were measured.Results : Our study indicated that FOXP3/ ROR- γt mRNA expression in PBMCs decreased significantlyin women experiencing URPL compared to the control group (1.13 ± 0.3 vs 3.79± 0.80, P=0.0001). 1,25VitD3 (50 nM) increased FOXP3 gene expression (1.91 ± 0.15 vs 1.22 ± 0.17, P=0.0001) while it did notsignificantly affect ROR- γt gene expression. 1,25 vitD treatment significantly increased FOXP3/ ROR- γtmRNA expression from baseline in the fetal loss group compared to that in the control group (1.94 ± 0.5vs 1.40 ± 0.42, P= 0.01). 1,25 VitD3 also increased GITR gene expression ( 3.05 ± 0.51 vs 0.59 ± 0.10 , P=0.017) in URPL women compared to the controls.Conclusion : Vitamin D deficiency may be a contributor to recurrent pregnancy loss and suggestssupplementation of women with Vit D pre-pregnancy may be protective against URPL via affecting Tregssignature genes; FOXP3 and GITR.

کلیدواژه ها:

Unexplained recurrent fetal loss ، FOXP3 ، ROR- γt ، GITR and CTLA-4 ، 1 ، 25VitD3