Loading...
 
Toggle Health Problems and D

Reduced fetal immune system stem cells if low Vitamin D at a point in pregnancy – Sept 2023

Prenatal vitamin D deficiency alters immune cell proportions of young adult offspring through alteration of long-term stem cell fates

bioRxiv. 2023 Sep 13;2023.09.11.557255. doi: 10.1101/2023.09.11.557255.Preprint
Koki Ueda, Shu Shien Chin, Noriko Sato, Miyu Nishikawa, Kaori Yasuda, Naoyuki Miyasaka, Betelehem Solomon Bera, Laurent Chorro, Reanna Doña-Termine, Wade R Koba, David Reynolds, Ulrich G Steidl, Gregoire Lauvau, John M Greally, Masako Suzuki

Vitamin D deficiency is a common deficiency worldwide, particularly among women of reproductive age.
During pregnancy, it increases the risk of immune-related diseases in offspring later in life.
However, exactly how the body remembers exposure to an adverse environment during development is poorly understood. Herein, we explore the effects of prenatal vitamin D deficiency on immune cell proportions in offspring using vitamin D deficient mice established by dietary manipulation. We show that prenatal vitamin D deficiency alters immune cell proportions in offspring by changing the transcriptional properties of genes downstream of vitamin D receptor signaling in hematopoietic stem and progenitor cells of both the fetus and adults. Further investigations of the associations between maternal vitamin D levels and cord blood immune cell profiles from 75 healthy pregnant women and their term babies also confirm that maternal vitamin D levels significantly affect immune cell proportions in the babies.
Thus, lack of prenatal vitamin D, particularly at the time of hematopoietic stem cell migration from the liver to the bone marrow, has long-lasting effects on immune cell proportions. This highlights the importance of providing vitamin D supplementation at specific stages of pregnancy.
 Download the PDF from Vitamin D Life

This is probably true - need peer review and other studies (comment by Vitamin D Life))

Vitamin D Life - Pregnancy category contains

886 items in Pregnancy category

 - see also

Vitamin D Life – Healthy pregnancies need lots of vitamin D contains

Problem
Vit. D
Reduces		Evidence
0. Chance of not conceiving3.4 times Observe
1. Miscarriage 2.5 times Observe
2. Pre-eclampsia 3.6 timesRCT
3. Gestational Diabetes 3 times RCT
4. Good 2nd trimester sleep quality 3.5 times Observe
5. Premature birth 2 times RCT
6. C-section - unplanned 1.6 timesObserve
     Stillbirth - OMEGA-3 4 timesRCT - Omega-3
7. Depression AFTER pregnancy 1.4 times RCT
8. Small for Gestational Age 1.6 times meta-analysis
9. Infant height, weight, head size
     within normal limits		 RCT
10. Childhood Wheezing 1.3 times RCT
11. Additional child is Autistic 4 times Intervention
12.Young adult Multiple Sclerosis 1.9 timesObserve
13. Preeclampsia in young adult 3.5 timesRCT
14. Good motor skills @ age 31.4 times Observe
15. Childhood Mite allergy 5 times RCT
16. Childhood Respiratory Tract visits 2.5 times RCT

RCT = Randomized Controlled Trial

99 STUDY REFERENCES
  1. Mostafa, W. Z. & Hegazy, R. A. Vitamin D and the skin: Focus on a complex relationship: A review. J. Advanc. Res. 6, 793-804 (2015).
  2. Bodnar, L. M. et al. Maternal vitamin D deficiency increases the risk of preeclampsia. J. Clin. Endocrinol. Metab. 92, 3517-3522 (2007).
  3. van der Pligt, P. et al. Associations of Maternal Vitamin D Deficiency with Pregnancy and Neonatal Complications in Developing Countries: A Systematic Review. Nutrients 10, (2018).
  4. Zosky, G. R. et al. Vitamin D deficiency at 16 to 20 weeks’ gestation is associated with impaired lung function and asthma at 6 years of age. Ann. Am. Thorac. Soc. 11,571-577 (2014).
  5. Weinert, L. S. & Silveiro, S. P. Maternal-fetal impact of vitamin D deficiency: a critical review. Matern. Child Health J. 19, 94-101 (2015).
  6. Hart, P. H. et al. Vitamin D in fetal development: findings from a birth cohort study. Pediatrics 135, e167-73 (2015).
  7. Gilani, S. & Janssen, P. Maternal Vitamin D Levels During Pregnancy and Their Effects on Maternal-Fetal Outcomes: A Systematic Review. J. Obstet. Gynaecol. Can. (2019) doi:10.1016/j.jogc.2019.09.013.
  8. Cashman, K. D. Vitamin D Requirements for the Future-Lessons Learned and Charting a Path Forward. Nutrients 10, (2018).
  9. Roth, D. E. et al. Vitamin D supplementation in pregnancy and lactation and infant growth. N. Engl. J. Med. 379, 535-546 (2018).
  10. Cashman, K. D. Vitamin D deficiency: defining, prevalence, causes, and strategies of addressing. Calcif. Tissue Int. 106, 14-29 (2020).
  11. Aspelund, T. et al. Effect of Genetically Low 25-Hydroxyvitamin D on Mortality Risk: Mendelian Randomization Analysis in 3 Large European Cohorts. Nutrients 11, (2019).
  12. Forrest, K. Y. Z. & Stuhldreher, W. L. Prevalence and correlates of vitamin D deficiency in US adults. Nutr. Res. 31, 48-54 (2011).
  13. Liu, X., Baylin, A. & Levy, P. D. Vitamin D deficiency and insufficiency among US adults: prevalence, predictors and clinical implications. Br. J. Nutr. 119, 928-936 (2018).
  14. Lips, P. Worldwide status of vitamin D nutrition. J. Steroid Biochem. Mol. Biol. 121, 297-300 (2010).
  15. Holick, M. F. Resurrection of vitamin D deficiency and rickets. J. Clin. Invest. 116, 2062-2072 (2006).
  16. Pike, J. W., Meyer, M. B., Lee, S.-M., Onal, M. & Benkusky, N. A. The vitamin D receptor: contemporary genomic approaches reveal new basic and translational insights. J. Clin. Invest. 127, 1146-1154 (2017).
  17. Yetgin, S. & Ozsoylu, S. Myeloid metaplasia in vitamin D deficiency rickets. Scand. J. Haematol. 28, 180-185 (1982).
  18. Panda, D. K. et al. Targeted ablation of the 25-hydroxyvitamin D 1alpha -hydroxylase enzyme: evidence for skeletal, reproductive, and immune dysfunction. Proc Natl Acad Sci USA 98, 7498­7503 (2001).
  19. Maka, N. et al. Vitamin D deficiency during pregnancy and lactation stimulates nephrogenesis in rat offspring. Pediatr. Nephrol. 23, 55-61 (2008).
  20. Gezmish, O. & Black, M. J. Vitamin D deficiency in early life and the potential programming of cardiovascular disease in adulthood. J. Cardiovasc. Transl. Res. 6, 588-603 (2013).
  21. Foong, R. E. et al. The effects of in utero vitamin D deficiency on airway smooth muscle mass and lung function. Am. J. Respir. Cell Mol. Biol. 53, 664-675 (2015).
  22. Hawes, J. E. et al. Maternal vitamin D deficiency alters fetal brain development in the BALB/c mouse. Behav. Brain Res. 286, 192-200 (2015).
  23. Wu, J., Zhong, Y., Shen, X., Yang, K. & Cai, W. Maternal and early-life vitamin D deficiency enhances allergic reaction in an ovalbumin-sensitized BALB/c mouse model. Food Nutr. Res. 62, (2018).
  24. Belenchia, A. M., Johnson, S. A., Ellersieck, M. R., Rosenfeld, C. S. & Peterson, C. A. In utero vitamin D deficiency predisposes offspring to long-term adverse adipose tissue effects. J. Endocrinol. 234, 301-313 (2017).
  25. Belenchia, A. M. et al. Maternal vitamin D deficiency during pregnancy affects expression of adipogenic-regulating genes peroxisome proliferator-activated receptor gamma (PPARy) and vitamin D receptor (VDR) in lean male mice offspring. Eur. J. Nutr. 57, 723-730 (2018).
  26. Reichetzeder, C. et al. Maternal vitamin D deficiency and fetal programming--lessons learned from humans and mice. Kidney Blood Press. Res. 39, 315-329 (2014).
  27. Nicholas, C. et al. Maternal vitamin D deficiency programs reproductive dysfunction in female mice offspring through adverse effects on the neuroendocrine axis. Endocrinology 157, 1535­1545 (2016).
  28. Liu, N. Q. et al. Dietary vitamin D restriction in pregnant female mice is associated with maternal hypertension and altered placental and fetal development. Endocrinology 154, 2270-2280 (2013).
  29. Xue, J., Schoenrock, S. A., Valdar, W., Tarantino, L. M. & Ideraabdullah, F. Y. Maternal vitamin D depletion alters DNA methylation at imprinted loci in multiple generations. Clin. Epigenetics 8, 107 (2016).
  30. Fernandes de Abreu, D. A. et al. Prenatal vitamin D deficiency induces an early and more severe experimental autoimmune encephalomyelitis in the second generation. Int. J. Mol. Sci. 13, 10911-10919 (2012).
  31. Maia-Ceciliano, T. C. et al. Maternal vitamin D-restricted diet has consequences in the formation of pancreatic islet/insulin-signaling in the adult offspring of mice. Endocrine 54, 60-69 (2016).
  32. Nascimento, F. A. M., Ceciliano, T. C., Aguila, M. B. & Mandarim-de-Lacerda, C. A. Maternal vitamin D deficiency delays glomerular maturity in F1 and F2 offspring. PLoS ONE 7, e41740 (2012).
  33. Nascimento, F. A. M., Ceciliano, T. C., Aguila, M. B. & Mandarim-de-Lacerda, C. A. Transgenerational effects on the liver and pancreas resulting from maternal vitamin D restriction in mice. J. Nutr. Sci. Vitaminol. 59, 367-374 (2013).
  34. Liang, Y. et al. Vitamin D deficiency worsens maternal diabetes induced neurodevelopmental disorder by potentiating hyperglycemia-mediated epigenetic changes. Ann. N. Y. Acad. Sci. (2020) doi:10.1111/nyas.14535.
  35. Lundy, K. et al. Vitamin D deficiency during development permanently alters liver cell composition and function. Front Endocrinol (Lausanne) 13, 860286 (2022).
  36. O’Kelly, J. et al. Normal myelopoiesis but abnormal T lymphocyte responses in vitamin D receptor knockout mice. J. Clin. Invest. 109, 1091-1099 (2002).
  37. Mathieu, C. et al. In vitro and in vivo analysis of the immune system of vitamin D receptor knockout mice. J. Bone Miner. Res. 16, 2057-2065 (2001).
  38. Yu, S. & Cantorna, M. T. Epigenetic reduction in invariant NKT cells following in utero vitamin D deficiency in mice. J. Immunol. 186, 1384-1390 (2011).
  39. Yu, S. & Cantorna, M. T. The vitamin D receptor is required for iNKT cell development. Proc Natl Acad Sci USA 105, 5207-5212 (2008).
  40. Yoshizawa, T. et al. Mice lacking the vitamin D receptor exhibit impaired bone formation, uterine hypoplasia and growth retardation after weaning. Nat. Genet. 16, 391-396 (1997).
  41. Gysemans, C. et al. Unaltered diabetes presentation in NOD mice lacking the vitamin D receptor. Diabetes 57, 269-275 (2008).
  42. Li, Y. C. et al. Targeted ablation of the vitamin D receptor: an animal model of vitamin D- dependent rickets type II with alopecia. Proc Natl Acad Sci USA 94, 9831-9835 (1997).
  43. Camargo, C. A. et al. Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. Am. J. Clin. Nutr. 85, 788-795 (2007).
  44. Brehm, J. M. et al. Serum vitamin D levels and severe asthma exacerbations in the Childhood Asthma Management Program study. J. Allergy Clin. Immunol. 126, 52-8.e5 (2010).
  45. Mirzaei, F. et al. Gestational vitamin D and the risk of multiple sclerosis in offspring. Ann. Neurol. 70, 30-40 (2011).
  46. Mulligan, M. L., Felton, S. K., Riek, A. E. & Bernal-Mizrachi, C. Implications of vitamin D deficiency in pregnancy and lactation. Am. J. Obstet. Gynecol. 202, 429.e1-9 (2010).
  47. Stene, L. C., Ulriksen, J., Magnus, P. & Joner, G. Use of cod liver oil during pregnancy associated with lower risk of Type I diabetes in the offspring. Diabetologia 43, 1093-1098 (2000).
  48. Vitamin D supplement in early childhood and risk for Type I (insulin-dependent) diabetes mellitus. The EURODIAB Substudy 2 Study Group. Diabetologia 42, 51-54 (1999).
  49. Pietras, E. M. et al. Functionally Distinct Subsets of Lineage-Biased Multipotent Progenitors Control Blood Production in Normal and Regenerative Conditions. Cell Stem Cell 17, 35-46 (2015).
  50. Challen, G. A., Boles, N., Lin, K. K.-Y. & Goodell, M. A. Mouse hematopoietic stem cell identification and analysis. Cytometry A 75, 14-24 (2009).
  51. Luis, T. C., Killmann, N. M. B. & Staal, F. J. T. Signal transduction pathways regulating hematopoietic stem cell biology: introduction to a series of Spotlight Reviews. Leukemia 26, 86­90 (2012).
  52. Battle, M. A. et al. Hepatocyte nuclear factor 4alpha orchestrates expression of cell adhesion proteins during the epithelial transformation of the developing liver. Proc Natl Acad Sci USA 103, 8419-8424 (2006).
  53. Boergesen, M. et al. Genome-wide profiling of liver X receptor, retinoid X receptor, and peroxisome proliferator-activated receptor a in mouse liver reveals extensive sharing of binding sites. Mol. Cell. Biol. 32, 852-867 (2012).
  54. Satija, R., Farrell, J. A., Gennert, D., Schier, A. F. & Regev, A. Spatial reconstruction of single­cell gene expression data. Nat. Biotechnol. 33, 495-502 (2015).
  55. Butler, A., Hoffman, P., Smibert, P., Papalexi, E. & Satija, R. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat. Biotechnol. 36, 411-420 (2018).
  56. Hafemeister, C. & Satija, R. Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression. Genome Biol. 20, 296 (2019).
  57. Wang, X. et al. Comparative analysis of cell lineage differentiation during hepatogenesis in humans and mice at the single-cell transcriptome level. Cell Res. 30, 1109-1126 (2020).
  58. Pinto do O, P., Kolterud, A. & Carlsson, L. Expression of the LIM-homeobox gene LH2 generates immortalized steel factor-dependent multipotent hematopoietic precursors. EMBO J. 17, 5744-5756 (1998).
  59. Pavethynath, S. et al. Metabolic and Immunological Shifts during Mid-to-Late Gestation Influence Maternal Blood Methylation of CPT1A and SREBF1. Int. J. Mol. Sci. 20, (2019).
  60. Sato, N. et al. Placenta mediates the effect of maternal hypertension polygenic score on offspring birth weight: a study of birth cohort with fetal growth velocity data. BMC Med. 19, 260 (2021).
  61. Lucas A., K. G., Meaghan C. ,. Kelly M. ,. Devin C. ,. John K. ,. Karl T. ,. Robert Lyle, Brock C. ,. Janine Felix. FlowSorted.CordBloodCombined.450k. Bioconductor (2019) doi:10.18129/b9.bioc.flowsorted.cordbloodcombined.450k.
  62. Gervin, K. et al. Systematic evaluation and validation of reference and library selection methods for deconvolution of cord blood DNA methylation data. Clin. Epigenetics 11, 125 (2019).
  63. Salas, L. A. et al. An optimized library for reference-based deconvolution of whole-blood biospecimens assayed using the Illumina HumanMethylationEPIC BeadArray. Genome Biol. 19, 64 (2018).
  64. Koestler, D. C. et al. Improving cell mixture deconvolution by identifying optimal DNA methylation libraries (IDOL). BMC Bioinformatics 17, 120 (2016).
  65. Imai, C. et al. Diet Quality and Its Relationship with Weight Characteristics in Pregnant Japanese Women: A Single-Center Birth Cohort Study. Nutrients 15, (2023).
  66. Imai, C. et al. Application of the Nutrient-Rich Food Index 9.3 and the Dietary Inflammatory Index for Assessing Maternal Dietary Quality in Japan: A Single-Center Birth Cohort Study. Nutrients 13, (2021).
  67. Loughran, S. J. et al. The transcription factor Erg is essential for definitive hematopoiesis and the function of adult hematopoietic stem cells. Nat. Immunol. 9, 810-819 (2008).
  68. Ng, A. P. et al. Erg is required for self-renewal of hematopoietic stem cells during stress hematopoiesis in mice. Blood 118, 2454-2461 (2011).
  69. Taoudi, S. et al. ERG dependence distinguishes developmental control of hematopoietic stem cell maintenance from hematopoietic specification. Genes Dev. 25, 251-262 (2011).
  70. Xie, Y. et al. Reduced erg dosage impairs survival of hematopoietic stem and progenitor cells. Stem Cells 35, 1773-1785 (2017).
  71. Cortes, M. et al. Developmental vitamin D availability impacts hematopoietic stem cell production. Cell Rep. 17, 458-468 (2016).
  72. Fraser, D. et al. Pathogenesis of hereditary vitamin-D-dependent rickets. An inborn error of vitamin D metabolism involving defective conversion of 25-hydroxyvitamin D to 1 alpha,25- dihydroxyvitamin D. N. Engl. J. Med. 289, 817-822 (1973).
  73. Yu, S., Bruce, D., Froicu, M., Weaver, V. & Cantorna, M. T. Failure of T cell homing, reduced CD4/CD8alphaalpha intraepithelial lymphocytes, and inflammation in the gut of vitamin D receptor KO mice. Proc Natl Acad Sci USA 105, 20834-20839 (2008).
  74. Wientroub, S., Hagan, M. P. & Reddi, A. H. Reduction of hematopoietic stem cells and adaptive increase in cell cycle rate in rickets. Am. J. Physiol. 243, C303-6 (1982).
  75. Gao, X., Xu, C., Asada, N. & Frenette, P. S. The hematopoietic stem cell niche: from embryo to adult. Development 145, (2018).
  76. Orkin, S. H. & Zon, L. I. Hematopoiesis: an evolving paradigm for stem cell biology. Cell 132, 631-644 (2008).
  77. Baron, M. H., Isern, J. & Fraser, S. T. The embryonic origins of erythropoiesis in mammals. Blood 119, 4828-4837 (2012).
  78. Soares-da-Silva, F., Peixoto, M., Cumano, A. & Pinto-do-O, P. Crosstalk between the hepatic and hematopoietic systems during embryonic development. Front. Cell Dev. Biol. 8, 612 (2020).
  79. Tavian, M. & Peault, B. Embryonic development of the human hematopoietic system. Int. J. Dev. Biol. 49, 243-250 (2005).
  80. Elgormus, Y., Okuyan, O. & Uzun, H. The relationship between hematological indices as indicators of inflammation and 25-hydroxyvitamin D3 status in newborns. BMC Pediatr. 23, 83 (2023).
  81. Xin, Y. et al. Accuracy of the neutrophil-to-lymphocyte ratio for the diagnosis of neonatal sepsis: a systematic review and meta-analysis. BMJ Open 12, e060391 (2022).
  82. Sumitro, K. R., Utomo, M. T. & Widodo, A. D. W. Neutrophil-to-Lymphocyte Ratio as an Alternative Marker of Neonatal Sepsis in Developing Countries. Oman Med. J. 36, e214 (2021).
  83. Panda, S. K., Nayak, M. K., Rath, S. & Das, P. The Utility of the Neutrophil-Lymphocyte Ratio as an Early Diagnostic Marker in Neonatal Sepsis. Cureus 13, e12891 (2021).
  84. Workneh Bitew, Z., Worku, T. & Alemu, A. Effects of vitamin D on neonatal sepsis: A systematic review and meta-analysis. Food Sci. Nutr. 9, 375-388 (2021).
  85. Can, E. & Can, C. The value of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) parameters in analysis with fetal malnutrition neonates. J. Perinat. Med. 47, 775-779 (2019).
  86. Chen, F. et al. Prenatal retinoid deficiency leads to airway hyperresponsiveness in adult mice. J. Clin. Invest. 124, 801-811 (2014).
  87. O’Callaghan-Gordo, C. et al. Vitamin D insufficient levels during pregnancy and micronuclei frequency in peripheral blood T lymphocytes mothers and newborns (Rhea cohort, Crete). Clin. Nutr. 36, 1029-1035 (2017).
  88. Andrews/Babraham Institute, S. FastQC: A quality control tool for high throughput sequence data. https://www.bioinformatics.babraham.ac.uk/projects/fastqc/ (2010).
  89. Martin, M. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet j. 17, 10 (2011).
  90. Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15-21 (2013).
  91. Wang, L., Wang, S. & Li, W. RSeQC: quality control of RNA-seq experiments. Bioinformatics 28, 2184-2185 (2012).
  92. Yu, G., Wang, L.-G., Han, Y. & He, Q.-Y. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16, 284-287 (2012).
  93. Stoeckius, M. et al. Cell Hashing with barcoded antibodies enables multiplexing and doublet detection for single cell genomics. Genome Biol. 19, 224 (2018).
  94. Gao, S. et al. Identification of HSC/MPP expansion units in fetal liver by single-cell spatiotemporal transcriptomics. Cell Res. 32, 38-53 (2022).
  95. Lachmann, A. et al. ChEA: transcription factor regulation inferred from integrating genome-wide ChIP-X experiments. Bioinformatics 26, 2438-2444 (2010).
  96. Chen, E. Y. et al. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinformatics 14, 128 (2013).
  97. Nishikawa, M. et al. Generation of 1,25-dihydroxyvitamin D3 in Cyp27b1 knockout mice by treatment with 25-hydroxyvitamin D3 rescued their rachitic phenotypes. J. Steroid Biochem. Mol. Biol. 185, 71-79 (2019).
  98. Higashi, T., Awada, D. & Shimada, K. Simultaneous determination of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in human plasma by liquid chromatography-tandem mass spectrometry employing derivatization with a Cookson-type reagent. Biol. Pharm. Bull. 24, 738-743 (2001).
  99. Houseman, E. A. et al. DNA methylation arrays as surrogate measures of cell mixture distribution. BMC Bioinformatics 13, 86 (2012).
Reduced fetal immune system stem cells if low Vitamin D at a point in pregnancy – Sept 2023        
599 visitors, last modified 25 Sep, 2023,
Printer Friendly Follow this page for updates
Pregnancy 834 Immunity 238
Page actions
Print
Edit Files 1

Attached files

ID Name Comment Uploaded Size Downloads
20127 low D to fetus, fewer imuune stem cells_CompressPdf.pdf admin 25 Sep, 2023 997.99 Kb 96