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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

(English title: Physiological Journal)

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2025; 71(4): 84-89

Vitamin D and p65-NF-kB: new pathogenetic mechanisms in the development of preeclampsia

I.V . Poladych, D.O. Govsieiev

  1. Bogomolets National Medical University, Kyiv
DOI: https://doi.org/10.15407/fz71.04.084


Abstract

Vitamin D deficiency represents a significant global concern among pregnant women, with prevalence rates varying from 28% to 96%, depending on the region. Over 65% of pregnant women experience suboptimal levels of this vitamin. The consequences of vitamin D deficiency on pregnancy include an increased risk of obstetric complications, particularly preeclampsia. One of the key mechanisms linking vitamin D deficiency to pregnancy pathologies is the activation of the pro-inflammatory nuclear factor NF-kB, specifically its p65 subunit, which influences placentation, angiogenesis, and immune adaptation. The study involved 155 pregnant women divided into three groups: those with vitamin D deficiency and preeclampsia, those with optimal vitamin D levels and preeclampsia, and a control group with uncomplicated pregnancies. The level and activity of p65 NF-kB were determined using enzyme-linked immunosorbent assay (ELISA). The results showed that vitamin D deficiency is associated with heightened activation of p65 NF-kB and increased inflammatory processes in the placenta. In the vitamin D deficiency group, p65 NF-kB activity was the highest (58.19 ± 0.25%) compared to only 29.44 ± 0.37% in the control group. The findings confirm the role of vitamin D in reducing the activation of NF-kB-dependent inflammatory pathways. Adequate vitamin D levels help mitigate inflammation, which is crucial for preventing preeclampsia and other obstetric complications. The influence of vitamin D on NF-kB offers promising perspectives for its use in the prevention of pregnancy pathologies.

Keywords: vitamin D deficiency; p65 subunit of nuclear factor kB (NF-kB); preeclampsia; pregnancy complications

Full text: (PDF, in English)

References

  1. Maugeri A, Barchitta M, Blanco I, Agodi A. Effects of Vitamin D supplementation during pregnancy on birth size: A systematic review and meta-analysis of randomized controlled trials. Nutrients. 2019;11(2):442.
  2. Meija L, Piskurjova A, Nikolajeva K, Aizbalte O, Rezgale R, Lejnieks A, et al. Vitamin D intake and serum levels in pregnant and postpartum women. Nutrients. 2023;15(15):3493. doi: 10.3390/nu15153493.
  3. Wang H, Zhang F, Li B, Fu M, Shan X, Ma Y . Three-stage pattern of rapid increase, plateau, and subsequent decline in vitamin D concentration during pregnancy among Chinese women: a large-scale survey. Front Nutr. 2023;10:1238389.
  4. Vestergaard AL, Christensen M, Andreasen MF, Larsen A, Bor P. Vitamin D in pregnancy (GRAVITD) - a randomised controlled trial identifying associations and mechanisms linking maternal Vitamin D deficiency to placental dysfunction and adverse pregnancy outcomes - study protocol. BMC Pregnancy Childbirth. 2023;23(1):177. doi: 10.1186/s12884-023-05484-x.
  5. Suresh S, Patel E, Mueller A, Morgan J, Lewandowski WL, V erlohren S, et al. The Additive Role of Angiogenic Markers for Women with Confirmed Preeclampsia. Am J Obstet Gynecol 2023;228:573.e1–11.
  6. Rouhani P, Mokhtari E, Lotfi K, Saneei P. The association between circulating 25-hydroxyvitamin D levels and preeclampsia: a systematic review and dose-response meta-analysis of epidemiologic studies with GRADE assessment. Nutr Rev. 2023;81(10):1267-1289.
  7. Reddy M, Palmer K, Rolnik DL, Wallace EM, Mol BW, Da Silva Costa F. Role of placental, fetal and maternal cardiovascular markers in predicting adverse outcome in women with suspected or confirmed pre-eclampsia. Ultrasound Obstet Gynecol. 2022;59(5):596-605.
  8. Lin CH, Lin PS, Lee MS, Lin CY, Sung YH, Li ST, et al. Associations between Vitamin D Deficiency and Carbohydrate Intake and Dietary Factors in Taiwanese Pregnant Women. Medicina (Kaunas). 2023;59(1):107.
  9. Abdallah HR, Abdelrazek AA, Youness ER, Orban HA, Mahmoud MA, El Sayed AH, et al. Assessment of vitamin status; A, E and D in Egyptian neonates with IUGR: a cross sectional study. BMC Pediatr. 2024;24(1):144.
  10. Wang H, Zhang F, Li B, Fu M, Shan X, Ma Y . Three-stage pattern of rapid increase, plateau, and subsequent decline in vitamin D concentration during pregnancy among Chinese women: a large-scale survey. Front Nutr. 2023;10:1238389.
  11. Cyprian F, Lefkou E, Varoudi K, Girardi G. Immuno-modulatory Effects of Vitamin D in Pregnancy and Beyond. Front Immunol. 2019;10:2739. Vitamin D and p65-NF-kB: new pathogenetic mechanisms in the development of preeclampsia 89
  12. Schröder-Heurich B, von Hardenberg S, Brodowski L, Kipke B, Meyer N, Borns K, et al. Vitamin D improves endothelial barrier integrity and counteracts inflammatory effects on endothelial progenitor cells. FASEB J. 2019;33(8):9142-53.
  13. Rana S, Lemoine E, Granger JP, Karumanchi SA. Preeclampsia: Pathophysiology, Challenges, and Perspectives. Circ Res. 2019;124(7):1094-112.
  14. Kim DH, Meza CA, Clarke H, Kim JS, Hickner RC. Vitamin D and Endothelial Function. Nutrients. 2020;12(2):575.
  15. Aouache R, Biquard L, Vaiman D, Miralles F. Oxidative stress in preeclampsia and placental diseases. Int J Mol Sci. 2018;19(5):1496.
  16. Ma Y, Yang Y, Lv M, Zhang Y, He Q, Zhang Y, et al. 1,25(OH)2D3 alleviates LPS-induced preeclampsia-like rats impairment in the protective effect by TLR4/NF-kB pathway. Placenta. 2022;130:34-41.
  17. Trefilio LM, Bottino L, de Carvalho Cardoso R, Montes GC, Fontes-Dantas FL. The impact of genetic variants related to vitamin D and autoimmunity: A systematic review. Heliyon. 2024;10(7).
  18. Gurkan N. Vitamin D supplementation during pregnancy inhibits the activation of fetal membrane NF- kB pathway. Eur Rev Med Pharmacol Sci. 2022;26(16):5926-31.
  19. Fantini C, Corinaldesi C, Lenzi A, Migliaccio S, Crescioli C. Vitamin D as a shield against Aging. Int J Mol Sci. 2023; 24(5):4546.
  20. Matias ML, Romao-Veiga M, Ribeiro VR, Nunes PR, Gomes VJ, Devides AC, et al. Progesterone and vitamin D downregulate the activation of the NLRP1/NLRP3 inflammasomes and TLR4-MyD88-NF-kB pathway in monocytes from pregnant women with preeclampsia. J Reprod Immun. 2021;144:103286.
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