Skip to main content Skip to main navigation menu Skip to site footer

Lipopolysaccharide-induced pregnant mice had decreased serum iron while maintaining hepcidin level and Hamp1 mRNA expression

  • Gilang Nugraha ,
  • Widjiati ,
  • Aryati ,
  • Citrawati Dyah Kencono Wungu ,
  • Harianto Notopuro ,
  • Win Darmanto ,
  • Agus Sulistyono ,
  • Hari Basuki Notobroto ,
  • Purwo Sri Rejeki ,


Introduction: Hepcidin is a hormone that regulates systemic iron homeostasis and is mostly produced in the liver. In pregnant women with inflammation, there are two opposing mechanisms in hepcidin expression: the suppression of hepcidin synthesis by pregnancy and the induction of hepcidin by inflammation. These conditions must receive special attention so clinicians can properly treat and manage pregnant women with inflammation. Therefore, this study aims to prove changes in hepcidin and serum iron levels in pregnant mice with inflammation.

Method: This study involved sixteen-second-week pregnant mice divided into two groups. Pregnant mice were injected with lipopolysaccharide (LPS) Escherichia coli serotype O111:B4 as much as 1 µg/g body weight intraperitoneally as the treatment group. In contrast, pregnant mice were injected with phosphate buffer saline (PBS) as a control group. Serum was measured using ELISA to determine hepcidin levels and colorimetry to determine serum iron. Mice livers were measured using Real-Time PCR to determine Hamp1 mRNA expression. The data obtained were analyzed using an independent t-test.

Result: Our results show that pregnant mice with inflammation show there was no difference in Hamp1 mRNA expression (p-value=0.163) and hepcidin level (p-value=0.789), but there was a significant difference in serum iron level (p-value=0.035).

Conclusion: This study demonstrates that inflammation in pregnancy does not affect changes in Hamp1 expression and hepcidin level but reduces serum iron, which could be caused by regulating hepcidin in the fetus.


  1. WHO. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Vitamin and Mineral Nutrition Information System. Switzerland: World Health Organization; 2011.
  2. Percy L, Mansour D, Fraser I. Iron deficiency and iron deficiency anaemia in women. Best Pract Res Clin Obstet Gynaecol. 2017;40(2017):55–67.
  3. Brannon PM, Taylor CL. Iron supplementation during pregnancy and infancy: Uncertainties and implications for research and policy. Nutrients. 2017;9(12):1–17.
  4. Friedrisch JR, Friedrisch BK. Prophylactic Iron Supplementation in Pregnancy: A Controversial Issue. Biochem Insights. 2017;10:117862641773773.
  5. Sangkhae V, Nemeth E. Regulation of the Iron Homeostatic Hormone Hepcidin. Adv Nutr An Int Rev J. 2017;8(1):126–36.
  6. Ginzburg YZ. Hepcidin-ferroportin axis in health and disease. Vitam Horm. 2019 Jan;110:17.
  7. Pagani A, Nai A, Silvestri L, Camaschella C. Hepcidin and Anemia: A Tight Relationship. Front Physiol. 2019 Oct;10:1294.
  8. Fisher AL, Nemeth E. Iron homeostasis during pregnancy. Am J Clin Nutr. 2017;106:1567S-1574S.
  9. Kulik-Rechberger B, Kościesza A, Szponar E, Domosud J. Hepcidin and iron status in pregnant women and full-term newborns in first days of life. Ginekol Pol. 2016;87(4):288–92.
  10. Koenig MD, Tussing-Humphreys L, Day J, Cadwell B, Nemeth E. Hepcidin and iron homeostasis during pregnancy. Vol. 6, Nutrients. MDPI AG; 2014. p. 3062–83.
  11. Yang Q, Jian J, Katz S, Abramson SB, Huang X. 17β-estradiol inhibits iron hormone hepcidin through an estrogen responsive element half-site. Endocrinology. 2012 Jul;153(7):3170–8.
  12. Finley C, Zhang C, Fewell JE. Sex steroid levels near the term of pregnancy do not alter lipopolysaccharide-induced fever in oophorectomized rats. Exp Physiol. 2015 Mar;100(3):323–30.
  13. Thielen N, van der Kraan P, van Caam A. TGFβ/BMP Signaling Pathway in Cartilage Homeostasis. Cells. 2019 Aug;8(9):969.
  14. Dituri F, Cossu C, Mancarella S, Giannelli G. The Interactivity between TGFβ and BMP Signaling in Organogenesis, Fibrosis, and Cancer. Cells. 2019 Sep;8(10):1130.
  15. Bertolino P, Holmberg R, Reissmann E, Andersson O, Berggren PO, Ibáñez CF. Activin B receptor ALK7 is a negative regulator of pancreatic β-cell function. Proc Natl Acad Sci U S A. 2008 May;105(20):7246–51.
  16. Bernard DJ, Lee KB, Santos MM. Activin B can signal through both ALK4 and ALK7 in gonadotrope cells. Reprod Biol Endocrinol. 2006 Oct;4:52.
  17. Moreira AC, Neves J V., Silva T, Oliveira P, Gomes MS, Rodrigues PN. Hepcidin-(In)dependent Mechanisms of Iron Metabolism Regulation during Infection by Listeria and Salmonella. Infect Immun. 2017 Sep;85(9).
  18. Lee YS, Kim YH, Jung YS, Kim KS, Kim DK, Na SY, et al. Hepatocyte toll-like receptor 4 mediates lipopolysaccharide-induced hepcidin expression. Exp Mol Med. 2017;49(12):e408.
  19. Wang Q, Du F, Qian ZM, Xiao HG, Zhu L, Wing HY, et al. Lipopolysaccharide induces a significant increase in expression of iron regulatory hormone hepcidin in the cortex and substantia nigra in rat brain. Endocrinology. 2008 Aug;149(8):3920–5.
  20. Merle U, Fein E, Gehrke SG, Stremmel W, Kulaksiz H. The Iron Regulatory Peptide Hepcidin Is Expressed in the Heart and Regulated by Hypoxia and Inflammation. Endocrinology. 2007 Jun;148(6):2663–8.
  21. Canali S, Core AB, Zumbrennen-Bullough KB, Merkulova M, Wang CY, Schneyer AL, et al. Activin B induces noncanonical SMAD1/5/8 signaling via BMP type I receptors in hepatocytes: Evidence for a role in hepcidin induction by inflammation in male mice. Endocrinology. 2016 Mar;157(3):1146–62.
  22. Van Eijk LT, John ASE, Schwoebel F, Summo L, Vauléon S, Zöllner S, et al. Effect of the antihepcidin Spiegelmer lexaptepid on inflammation-induced decrease in serum iron in humans. Blood. 2014 Oct;124(17):2643.
  23. Wrighting DM, Andrews NC. Interleukin-6 induces hepcidin expression through STAT3. Blood. 2006 Nov;108(9):3204–9.
  24. Charlebois E, Pantopoulos K. Iron overload inhibits BMP/SMAD and IL-6/STAT3 signaling to hepcidin in cultured hepatocytes. PLoS One. 2021 Jun;16(6).
  25. Varga E, Pap R, Jánosa G, Sipos K, Pandur E. IL-6 Regulates Hepcidin Expression Via the BMP/SMAD Pathway by Altering BMP6, TMPRSS6 and TfR2 Expressions at Normal and Inflammatory Conditions in BV2 Microglia. Neurochem Res. 2021 May;46(5):1224.
  26. Soldin OP, Guo T, Weiderpass E, Tractenberg RE, Hilakivi-Clarke L, Soldin SJ. Steroid hormone levels in pregnancy and 1 year postpartum using isotope dilution tandem mass spectrometry. Fertil Steril. 2005 Sep;84(3):701.
  27. Johnson MS, Jackson DL, Schust DJ. Endocrinology of Pregnancy. Encycl Reprod. 2021 Mar;469–76.
  28. Fuentes N, Silveyra P. Estrogen receptor signaling mechanisms. In: Advances in Protein Chemistry and Structural Biology. Academic Press Inc.; 2019. p. 135–70.
  29. Lehtihet M, Bonde Y, Beckman L, Berinder K, Hoybye C, Rudling M, et al. Circulating Hepcidin-25 Is Reduced by Endogenous Estrogen in Humans. PLoS One. 2016 Feb;11(2):e0148802.
  30. Hou Y, Zhang S, Wang L, Li J, Qu G, He J, et al. Estrogen regulates iron homeostasis through governing hepatic hepcidin expression via an estrogen response element. Gene. 2012 Dec;511(2):398–403.
  31. Sangkhae V, Fisher AL, Chua KJ, Ruchala P, Ganz T, Nemeth E. Maternal hepcidin determines embryo iron homeostasis in mice. Blood. 2020 Nov;136(19):2206.
  32. Tabbah SM, Buhimschi CS, Rodewald-Millen K, Pierson CR, Bhandari V, Samuels P, et al. Hepcidin, an Iron Regulatory Hormone of Innate Immunity, is Differentially Expressed in Premature Fetuses With Early-Onset Neonatal Sepsis. Am J Perinatol. 2018 Jul;35(9):865.
  33. Kämmerer L, Mohammad G, Wolna M, Robbins PA, Lakhal-Littleton S. Fetal liver hepcidin secures iron stores in utero. Blood. 2020 Sep;136(13):1549.

How to Cite

Nugraha, G., Widjiati, Aryati, Wungu, C. D. K. ., Notopuro, H. ., Darmanto, W. ., Sulistyono, A. ., Notobroto, H. B. ., & Rejeki, P. S. . (2023). Lipopolysaccharide-induced pregnant mice had decreased serum iron while maintaining hepcidin level and Hamp1 mRNA expression. Bali Medical Journal, 12(2), 1881–1885.




Search Panel