Ukr.Biochem.J. 2025; Volume 97, Issue 4, Jul-Aug, pp. 34-42

doi: https://doi.org/10.15407/ubj97.04.034

Experimental preeclampsia development depends on vitamin D(3) status in female wistar rats

10.09.2025   Uncategorized   No comments

I. V. Poladych1*, I. O. Shymanskyi2, M. M. Veliky2, D. O. Govsieiev1

1Department of Obstetrics and Gynecology No 1,
Bogomolets National Medical University, Kyiv, Ukraine;
2Department of Biochemistry of Vitamins and Coenzymes,
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: iren.poladich@gmail.com

Received: 08 May 2025; Revised: 08 August 2025;
Accepted: 12 September 2025; Available on-line: 17 September 2025

Deficiency of vitamin D3 during pregnancy is a widespread challenge associated with increased risk of complications, particularly preeclampsia (PE), a serious condition characterized by hypertension with proteinuria. This research aimed to study the experimental preeclampsia rates in pregnant rats depending on the vitamin D3 supply. Eight-week-old female Wistar rats were divided into three experimental groups: control; vitamin D3-deficient for 60 days before mating; vitamin D3-deficient with oral vitamin D3 supplement (1000 IU/kg b.w.t) two weeks before mating. Subgroups with and without PE induction were analyzed. PE was induced by administration of Nω-nitro-L-arginine methyl ester (L-NAME). The blood level of vitamin D3 was measu­red using a 25-Hydroxyvitamin D3 ELISA kit. Proteinuria was assessed using semi-quantitative urine test strips “Prototest”. The highest blood pressure and proteinuria levels were recorded in animals with combined vitamin D3 deficiency and induced preeclampsia. Administration of vitamin D3 contributed to normalization of hemodynamic parameters and kidney function, indicating the importance of an adequate vitamin D3 status for pregnancy health and PE prevention.

Keywords: , , , ,

References:

  1. Holick MF. The one-hundred-year anniversary of the discovery of the sunshine vitamin D3: historical, personal experience and evidence-based perspectives. Nutrients. 2023;15(3):593. PubMed, PubMed, CrossRef
  2. Bikle DD. Vitamin D: newer concepts of its metabolism and function at the basic and clinical level. J Endocr Soc. 2020;4(2):bvz038. PubMed, PubMed, CrossRef
  3. Carlberg C, Raczyk M, Zawrotna N. Vitamin D: A master example of nutrigenomics. Redox Biol. 2023;62:102695. PubMed, PubMed, CrossRef
  4. Carlberg C. Genomic signaling of vitamin D. Steroids. 2023;198:109271. PubMed, CrossRef
  5. Grygorieva N, Tronko M, Kovalenko V, Komisarenko S, Tatarchuk T, Dedukh N, Veliky M, Strafun S, Komisarenko Y, Kalashnikov A, Orlenko V, Pankiv V, Shvets O, Gogunska I, Regeda S. Ukrainian consensus on diagnosis and management of vitamin D deficiency in adults. Nutrients. 2024;16(2):270. PubMed, PubMed, CrossRef
  6. 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. PubMed, PubMed, CrossRef
  7. Suresh S, Patel E, Mueller A, Morgan J, Lewandowski WL, Verlohren S, von Dadelszen P, Magee LA, Rana S. The additive role of angiogenic markers for women with confirmed preeclampsia. Am J Obstet Gynecol. 2023;228(5):573.e1-573.e11. PubMed, CrossRef
  8. 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. PubMed, CrossRef
  9. 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. PubMed, CrossRef
  10. Schröder-Heurich B, von Hardenberg S, Brodowski L, Kipke B, Meyer N, Borns K, von Kaisenberg CS, Brinkmann H, Claus P, von Versen-Höynck F. Vitamin D improves endothelial barrier integrity and counteracts inflammatory effects on endothelial progenitor cells. FASEB J. 2019;33(8):9142-9153. PubMed, CrossRef
  11. Ramdin S, Baijnath S, Naicker T, Govender N. The clinical value of rodent models in understanding preeclampsia development and progression. Curr Hypertens Rep. 2023;25(6):77-89. PubMed, PubMed, CrossRef
  12. Bakrania BA, George EM, Granger JP. Animal models of preeclampsia: investigating pathophysiology and therapeutic targets. Am J Obstet Gynecol. 2022;226(2S):S973-S987. PubMed, PubMed, CrossRef
  13. Shu W, Li H, Gong H, Zhang M, Niu X, Ma Y, Zhang X, Cai W, Yang G, Wei M, Yang N, Li Y. Evaluation of blood vessel injury, oxidative stress and circulating inflammatory factors in an L-NAME-induced preeclampsia-like rat model. Exp Ther Med. 2018;16(2):585-594. PubMed, PubMed, CrossRef
  14. Nema J , Sundrani D , Joshi S . Prenatal vitamin D supplementation reduces blood pressure and improves placental angiogenesis in an animal model of preeclampsia. Food Funct. 2020;11(12):10413-10422. PubMed, CrossRef
  15. Vitoratos N, Lambrinoudaki I, Rizos D, Armeni E, Alexandrou A, Creatsas G. Maternal circulating osteoprotegerin and soluble RANKL in pre-eclamptic women. Eur J Obstet Gynecol Reprod Biol. 2011;154(2):141-145. PubMed, CrossRef
  16. Riasniy VM, Apukhovska LI , Veliky NN, Shymanskyy IO, Labudzynskyi DO, Komisarenko SV. Immunomodulatory effects of vitamin D(3) and bisphosphonates in nutritional osteoporosis in rats. Ukr Biokhim Zhurn. 2012;84(2):73-80. (In Ukrainian). PubMed
  17. Durá-Travé T, Gallinas-Victoriano F. Pregnancy, Breastfeeding, and Vitamin D. Int J Mol Sci. 2023;24(15):11881. PubMed, PubMed, CrossRef
  18. Wagner CL, Hollis BW. The extraordinary metabolism of vitamin D. Elife. 2022;11:e77539. PubMed, PubMed, CrossRef
  19. Bianconi V, Mannarino MR, Figorilli F, Cosentini E, Batori G, Marini E, Lombardini R, Gargaro M, Fallarino F, Scarponi AM, Sahebkar A, Pirro M. Prevalence of vitamin D deficiency and its prognostic impact on patients hospitalized with COVID-19. Nutrition. 2021;91-92:111408. PubMed, PubMed, CrossRef
  20. Verlohren S, Dröge LA. The diagnostic value of angiogenic and antiangiogenic factors in differential diagnosis of preeclampsia. Am J Obstet Gynecol. 2022;226(2S):S1048-S1058. PubMed, CrossRef
  21. 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. PubMed, PubMed, CrossRef
  22. Abbasalizadeh S, Abam F, Mirghafourvand M, Abbasalizadeh F, Taghavi S, Hajizadeh K. Comparing levels of vitamin D, calcium and phosphorus in normotensive pregnant women and pregnant women with preeclampsia. J Obstet Gynaecol. 2020;40(8):1069-1073. PubMed, CrossRef
  23. Benachi A, Baptiste A, Taieb J, Tsatsaris V, Guibourdenche J, Senat MV, Haidar H, Jani J, Guizani M, Jouannic JM, Haguet MC, Winer N, Masson D, Courbebaisse M, Elie C, Souberbielle JC. Relationship between vitamin D status in pregnancy and the risk for preeclampsia: A nested case-control study. Clin Nutr. 2020;39(2):440-446. PubMed, CrossRef
  24. Sparaco M, Bonavita S. Vitamin D Supplementation: Effect on Cytokine Profile in Multiple Sclerosis. J Clin Med. 2024;13(3):835. PubMed, PubMed, CrossRef
  25. Bi WG, Nuyt AM, Weiler H, Leduc L, Santamaria C, Wei SQ. Association between vitamin D supplementation during pregnancy and offspring growth, morbidity, and mortality: a ystematic review and meta-analysis. JAMA Pediatr. 2018;172(7):635-645. PubMed, PubMed, CrossRef
  26.  Liu NQ, Ouyang Y, Bulut Y, Lagishetty V, Chan SY, Hollis BW, Wagner C, Equils O, Hewison M. Dietary vitamin D restriction in pregnant female mice is associated with maternal hypertension and altered placental and fetal development. Endocrinology. 2013;154(7):2270-2280. PubMed, CrossRef
  27. Rana S, Lemoine E, Granger JP, Karumanchi SA. Preeclampsia: pathophysiology, challenges, and perspectives. Circ Res. 2019;124(7):1094-1112. PubMed, CrossRef
  28. Kim DH, Meza CA, Clarke H, Kim JS, Hickner RC. Vitamin D and endothelial function. Nutrients. 2020;12(2):575.
    PubMed, PubMed, CrossRef
  29. Aouache R, Biquard L, Vaiman D, Miralles F. Oxidative Stress in Preeclampsia and Placental Diseases. Int J Mol Sci. 2018;19(5):1496. PubMed, PubMed, CrossRef
  30. Ma Y, Yang Y, Lv M, Zhang Y, He Q, Zhang Y, Su H, Deng X, Qian Y. 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. PubMed, CrossRef
  31. Poladych IV. Vitamin D in the genesis of preeclampsia: current understanding of the problem (literature review). Bull Probl Biol Med. 2024;175(4):113-122. CrossRef
  32. Lukyanova EM, Antipkin YuG, Omelchenko LI, Apukhovskaya LI. Vitamin D and its role in ensuring the health of children and pregnant women. Monograph. K. Iz-vo “Expert”. 2005. 230 p.
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