Ukr.Biochem.J. 2026; Volume 98, Issue 1, Jan-Feb, pp. 37-48
doi: https://doi.org/10.15407/ubj98.01.037
Fibroblast growth factor 23, calcium and phosphate serum levels in experimental preeclampsia: impact of vitamin D(3) status
I. V. Poladych1*, I. O. Shymanskyi2, A. V. Khomenko2,
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: 25 August 2025; Revised: 02 October2025;
Accepted: 30 January 2026; Available on-line: 23 February 2026
Preeclampsia (PE) is a major cause of maternal and perinatal morbidity, with its pathogenesis involving, in particular, impaired mineral homeostasis. Recent evidence suggest that fibroblast growth factor 23 (FGF23), a key regulator of phosphate balance and vitamin D3 metabolism, may contribute to pregnancy complications, however, its role in PE remains poorly understood. This study aimed to evaluate serum FGF23 level and its relationship with vitamin D3 and calcium–phosphate balance at preeclampsia development in animal experimental model. Thirty-five Wistar female rats were divided into three groups: controls on a standard diet; vitamin D3-deficient rats; vitamin D3-deficient rats supplemented with cholecalciferol. Within each group, PE was induced by Nω-nitro-L-arginine methyl ester administration. Serum concentrations of 25(OH)D3, FGF23, parathyroid hormone (PTH), total calcium, inorganic phosphate, and alkaline phosphatase (ALP) activity were determined by ELISA and biochemical assays. It was shown that vitamin D3 deficiency was accompanied by hypocalcemia, hypophosphatemia, elevated FGF23 and increased ALP activity in the serum. Supplementation with vitamin D3 increased 25(OH)D3, markedly reduced FGF23 levels and normalized mineral parameters. Induction of PE caused significant disturbances in calcium–phosphate status, hypertension, and 100% mortality of vitamin D3-deficient animals. In the presence of preeclampsia vitamin D3 efficacy was limited. In PE group, despite of vitamin D3 supplementation, serum FGF23 was markedly elevated, indicating impaired vitamin D3 metabolism. Our findings demonstrate that vitamin D3 deficiency amplifies PE severity through disruption of mineral homeostasis and FGF23 dependent signaling.
Keywords: 25OHD3, calcium–phosphate metabolism, L-NAME, preeclampsia, vitamin D3 deficiency
References:
- Rana S, Lemoine E, Granger JP, Karumanchi SA. Preeclampsia: Pathophysiology, Challenges, and Perspectives. Circ Res. 2019;124(7):1094-1112. PubMed, CrossRef
- Opichka MA, Rappelt MW, Gutterman DD, Grobe JL, McIntosh JJ. Vascular Dysfunction in Preeclampsia. Cells. 2021;10(11):3055. PubMed, PubMedCentral, CrossRef
- Moura TDB, Nunes FB, Crestani BDV, Araujo TFC, Hanauer EL, Corleta HVE, Branchini G. Preeclampsia and transport of ions and small molecules: A literature review. Placenta. 2024;156:77-91. PubMed, CrossRef
- Javandoust Gharehbagh F, Soltani-Zangbar MS, Yousefzadeh Y. Immunological mechanisms in preeclampsia: A narrative review. J Reprod Immunol. 2024;164:104282. PubMed, CrossRef
- 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
- 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
- Bøllehuus Hansen L, Kaludjerovic J, Nielsen JE, Rehfeld A, Poulsen NN, Ide N, Skakkebaek NE, Frederiksen H, Juul A, Lanske B, Blomberg Jensen M. Influence of FGF23 and Klotho on male reproduction: Systemic vs direct effects. FASEB J. 2020;34(9):12436-12449. PubMed, CrossRef
- 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, PubMedCentral, CrossRef
- 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, PubMedCentral, CrossRef
- Haussler MR, Livingston S, Sabir ZL, Haussler CA, Jurutka PW. Vitamin D Receptor Mediates a Myriad of Biological Actions Dependent on Its 1,25-Dihydroxyvitamin D Ligand: Distinct Regulatory Themes Revealed by Induction of Klotho and Fibroblast Growth Factor-23. JBMR Plus. 2020;5(1):e10432. PubMed, PubMedCentral, CrossRef
- Carlberg C, Raczyk M, Zawrotna N. Vitamin D: A master example of nutrigenomics. Redox Biol. 2023;62:102695. PubMed, PubMedCentral, CrossRef
- 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
- 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
- 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
- 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, PubMedCentral, CrossRef
- Mansur JL, Oliveri B, Giacoia E, Fusaro D, Costanzo PR. Vitamin D: Before, during and after Pregnancy: Effect on Neonates and Children. Nutrients. 2022;14(9):1900. PubMed, PubMedCentral, CrossRef
- You Z, Mei H, Zhang Y, Song D, Zhang Y, Liu C. The effect of vitamin D deficiency during pregnancy on adverse birth outcomes in neonates: a systematic review and meta-analysis. Front Pediatr. 2024;12:1399615. PubMed, PubMedCentral, CrossRef
- Shymanskyi I.O., Lisakovska O.O., Mazanova A.O., Veliky M.M. Vitamin D in transcriptional regulation of immune response and inflammation. Advances in Medicine and Biology. Ed. Leon V. Berhardt. NOVA science publisher; 2021. V. 183. P. 1-83.
- Kiely ME, Wagner CL, Roth DE. Vitamin D in pregnancy: Where we are and where we should go. J Steroid Biochem Mol Biol. 2020;201:105669. PubMed, CrossRef
- Stenhouse C, Halloran KM, Newton MG, Gaddy D, Suva LJ, Bazer FW. Novel mineral regulatory pathways in ovine pregnancy: I. phosphate, klotho signaling, and sodium-dependent phosphate transporters. Biol Reprod. 2021;104(5):1084-1096. PubMed, CrossRef
- 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, PubMedCentral, CrossRef
- Stenhouse C, Halloran KM, Newton MG, Gaddy D, Suva LJ, Bazer FW. Novel mineral regulatory pathways in ovine pregnancy: II. Calcium-binding proteins, calcium transporters, and vitamin D signaling. Biol Reprod. 2021;105(1):232-243. PubMed, CrossRef
- Fahrleitner A, Dobnig H, Obernosterer A, Pilger E, Leb G, Weber K, Kudlacek S, Obermayer-Pietsch BM. Vitamin D deficiency and secondary hyperparathyroidism are common complications in patients with peripheral arterial disease. J Gen Intern Med. 2002;17(9):663-669. PubMed, PubMedCentral, CrossRef
- Kazemian E, Madreseh E, Azizi F, Ashrafivand S, Gargari SS, Mansournia MA, Wagner CL, Amouzegar A. The association of parathyroid hormone with serum 25-hydroxyvitamin during pregnancy. J Nutr Sci. 2023;12:e1. PubMed, PubMedCentral, CrossRef
- Wagner CL, Hollis BW. The extraordinary metabolism of vitamin D. Elife. 2022;11:e77539. PubMed, PubMedCentral, CrossRef
- Durá-Travé T, Gallinas-Victoriano F. Pregnancy, Breastfeeding, and Vitamin D. Int J Mol Sci. 2023;24(15):11881. PubMed, PubMedCentral, CrossRef
- 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, PubMedCentral, CrossRef
- 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
- 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
- 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 Systematic Review and Meta-analysis. JAMA Pediatr. 2018;172(7):635-645. PubMed, PubMedCentral, CrossRef
- 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.
- 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
- Aouache R, Biquard L, Vaiman D, Miralles F. Oxidative Stress in Preeclampsia and Placental Diseases. Int J Mol Sci. 2018;19(5):1496. PubMed, PubMedCentral, CrossRef
- AlSubai A, Baqai MH, Agha H, Shankarlal N, Javaid SS, Jesrani EK, Golani S, Akram A, Qureshi F, Ahmed S, Saran S. Vitamin D and preeclampsia: A systematic review and meta-analysis. SAGE Open Med. 2023;11:20503121231212093. PubMed, PubMedCentral, CrossRef
- 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, PubMedCentral, CrossRef
- 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 - Sugulle M, Fiskå BS, Jacobsen DP, Fjeldstad HE, Staff AC. Placental Senescence and the Two-Stage Model of Preeclampsia. Am J Reprod Immunol. 2024;92(1):e13904. PubMed, CrossRef
- Chau K, Welsh M, Makris A, Hennessy A. Progress in preeclampsia: the contribution of animal models. J Hum Hypertens. 2022;36(8):705-710. PubMed, PubMedCentral, CrossRef
- Riasniy VM, Apukhovska LI, Veliky NN, Shymanskyy IO, Labudzynskyi DO, Komisarenko SV. Immunomodulatory effects of vitamin D3 and bisphosphonates in nutritional osteoporosis in rats. Ukr Biokhim Zhurn. 2012;84(2):73-80. (In Ukrainian). PubMed
- 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, PubMedCentral, CrossRef
- Xie H, Bastepe I, Zhou W, Ay B, Ceraj Z, Portales-Castillo IA, Liu ES, Burnett-Bowie SM, Jüppner H, Rhee EP, Bastepe M, Simic P. 1,25-Dihydroxyvitamin D3 regulates furin-mediated FGF23 cleavage. JCI Insight. 2023;8(17):e168957. PubMed, PubMedCentral, CrossRef
- Martínez-Heredia L, Canelo-Moreno JM, García-Fontana B, Muñoz-Torres M. Non-Classical Effects of FGF23: Molecular and Clinical Features. Int J Mol Sci. 2024;25(9):4875. PubMed, PubMedCentral, CrossRef
- Poladych IV, Shymanskyi IO, Veliky MM, Govsieiev DO. Experimental preeclampsia development depends on vitamin D(3) status in female wistar rats. Ukr Biochem J. 2025;97(4):34-42. CrossRef
This work is licensed under a Creative Commons Attribution 4.0 International License.







