Elham Abdollahi1,2,3, Nafiseh Saghafi4, Seyed Abdolrahim Rezaee5,6, Maryam Rastin7, Lida Jarahi8, Vicki Clifton9, Houshang Rafatpanah5,6. 1. Halal Research Center of IRI, FDA, Tehran, Iran. 2. Department of Medical Immunology and Allergy, Student Research Committee, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 3. Graduate Research Trainee in Mater Research Institute-University of Queensland, Translational Research Institute, South Brisbane, Australia. 4. Department of Gynecology Oncology, Woman Health Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. 5. Research Center for HIV/AIDS, HTLV and Viral Hepatitis, Iranian Academic Center for Education, Culture and Research (ACECR), Mashhad Branch, Mashhad, Iran. 6. Inflammation and Inflammatory Diseases Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 7. Immunology Research Center, BuAli Research Institute, Department of Immunology and Allergy, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 8. Department of Community Medicine, School of Medicine, Mashhad University of Medical Sciences Mashhad, Iran. 9. Pregnancy and Development, Mater Research Institute, University of Queensland, Translational Research Institute, South Brisbane, Australia.
Abstract
Background: 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. Methods: 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. Results: 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. Conclusion: 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.
Background: Vitamin Dinsufficiency 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. Methods: 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. Results: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 URPLwomen compared to the controls. Conclusion:Vitamin Ddeficiency 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.
Authors: S A Krieg; X Fan; Y Hong; Q-X Sang; A Giaccia; L M Westphal; R B Lathi; A J Krieg; N R Nayak Journal: Mol Hum Reprod Date: 2012-04-14 Impact factor: 4.025