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Effects of vitamin C, vitamin E, and molecular hydrogen on the placental function in trophoblast cells

Abstract

Aim

This study aimed to investigate the effects of three different antioxidants, namely vitamin C, vitamin E, and molecular hydrogen, on cytotrophoblasts in vitro.

Methods

Two trophoblast cell lines, JAR and JEG-3, were exposed to different concentrations of vitamin C (0, 25, 50, 100, 500, 1,000, 5,000 μmol/L), vitamin E (0, 25, 50, 100, 500, 1,000, 5,000 μmol/L), and molecular hydrogen (0, 25, 50, 100, 500 μmol/L) for 48 h. The cell viability was detected using the MTS assay. The secretion of human chorionic gonadotropin (hCG) and the tumor necrosis factor-α (TNF-α) were assessed and the expression of TNF-α mRNA was observed by real-time RT-PCR.

Results

Cell viability was significantly suppressed by 500 μmol/L vitamins C and E (P < 0.05), but not by 500 μmol/L molecular hydrogen (P > 0.05). The expression of TNF-α was increased by 100 μmol/L vitamin C and 50 μmol/L vitamins E, separately or combined (P < 0.05), but not by molecular hydrogen (0–500 μmol/L), as validated by real-time RT-PCR. But the secretion of hCG was both inhibited by 50–500 μmol/L molecular hydrogen and high levels of vitamin C and E, separately or combined.

Conclusion

High levels of antioxidant vitamins C and E may have significant detrimental effects on placental function, as reflected by decreased cell viability and secretion of hCG; and placental immunity, as reflected by increased production of TNF-a. Meanwhile hydrogen showed no such effects on cell proliferation and TNF-α expression, but it could affect the level of hCG, indicating hydrogen as a potential candidate of antioxidant in the management of preeclampsia (PE) should be further studied.

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References

  1. 1.

    Salimi S et al (2014) The early-onset preeclampsia is associated with MTHFR and FVL polymorphisms. Arch Gynecol Obstet. doi:10.1007/s00404-014-3561-5

  2. 2.

    Yang X et al (2012) Analysis of the original causes of placental oxidative stress in normal pregnancy and pre-eclampsia: a hypothesis. J Matern Fetal Neonatal Med 25(7):884–888

  3. 3.

    Roberts JM, Hubel CA (1999) Is oxidative stress the link in the two-stage model of pre-eclampsia? Lancet 354(9181):788–789

  4. 4.

    Uzunlar O et al (2014) Is there an association between liver type fatty acid binding protein and severity of preeclampsia? Arch Gynecol Obstet. doi:10.1007/s00404-014-3540-x

  5. 5.

    Serdar Z et al (2003) Lipid and protein oxidation and antioxidant function in women with mild and severe preeclampsia. Arch Gynecol Obstet 268(1):19–25

  6. 6.

    Suhail M, Faizul Suhail M, Khan H (2008) Role of vitamins C and E in regulating antioxidant and pro-oxidant markers in preeclampsia. J Clin Biochem Nutr 43(3):210–220

  7. 7.

    Spinnato JA 2nd et al (2007) Antioxidant therapy to prevent preeclampsia: a randomized controlled trial. Obstet Gynecol 110(6):1311–1318

  8. 8.

    Rumbold A et al (2008) Antioxidants for preventing pre-eclampsia. Cochrane Database Syst Rev 1:CD004227

  9. 9.

    Rodrigo R et al (2005) Pathophysiological basis for the prophylaxis of preeclampsia through early supplementation with antioxidant vitamins. Pharmacol Ther 107(2):177–197

  10. 10.

    Polyzos NP et al (2007) Combined vitamin C and E supplementation during pregnancy for preeclampsia prevention: a systematic review. Obstet Gynecol Surv 62(3):202–206

  11. 11.

    Gilgun-Sherki Y et al (2002) Antioxidant therapy in acute central nervous system injury: current state. Pharmacol Rev 54(2):271–284

  12. 12.

    Aris A et al (2008) Detrimental effects of high levels of antioxidant vitamins C and E on placental function: considerations for the vitamins in preeclampsia (VIP) trial. J Obstet Gynaecol Res 34(4):504–511

  13. 13.

    Poston L et al (2006) Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial. Lancet 367(9517):1145–1154

  14. 14.

    Ohsawa I et al (2007) Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med 13(6):688–694

  15. 15.

    Yang X et al (2011) Protective effects of hydrogen-rich saline in preeclampsia rat model. Placenta 32(9):681–686

  16. 16.

    Kharb S (2000) Vitamin E and C in preeclampsia. Eur J Obstet Gynecol Reprod Biol 93(1):37–39

  17. 17.

    Rumbold A et al (2005) Antioxidants for preventing pre-eclampsia. Cochrane Database Syst Rev 4:CD004227

  18. 18.

    Tao YX et al (1995) Human intermediate trophoblasts express chorionic gonadotropin/luteinizing hormone receptor gene. Biol Reprod 53(4):899–904

  19. 19.

    Han SW, Lei ZM, Rao CV (1999) Treatment of human endometrial stromal cells with chorionic gonadotropin promotes their morphological and functional differentiation into decidua. Mol Cell Endocrinol 147(1–2):7–16

  20. 20.

    Chaouat G et al (1995) Immuno-endocrine interactions in early pregnancy. Hum Reprod 10(Suppl 2):55–59

  21. 21.

    Kharfi A et al (2005) Human chorionic gonadotropin (hCG) may be a marker of systemic oxidative stress in normotensive and preeclamptic term pregnancies. Clin Biochem 38(8):717–721

  22. 22.

    Kharfi Aris A et al (2007) Dual action of H2O2 on placental hCG secretion: implications for oxidative stress in preeclampsia. Clin Biochem 40(1–2):94–97

  23. 23.

    Toth P et al (2001) Clinical importance of vascular LH/hCG receptors—a review. Reprod Biol 1(2):5–11

  24. 24.

    Kharfi A et al (2003) Trophoblastic remodeling in normal and preeclamptic pregnancies: implication of cytokines. Clin Biochem 36(5):323–331

  25. 25.

    Hunt JS, Chen HL, Miller L (1996) Tumor necrosis factors: pivotal components of pregnancy? Biol Reprod 54(3):554–562

  26. 26.

    Kharfi A et al (2006) Dissociation between increased apoptosis and expression of the tumor necrosis factor-alpha system in term placental villi with preeclampsia. Clin Biochem 39(6):646–651

  27. 27.

    Li Y et al (1992) Trophoblast-derived tumor necrosis factor-alpha induces release of human chorionic gonadotropin using interleukin-6 (IL-6) and IL-6-receptor-dependent system in the normal human trophoblasts. J Clin Endocrinol Metab 74(1):184–191

  28. 28.

    Yui J et al (1994) Cytotoxicity of tumour necrosis factor-alpha and gamma-interferon against primary human placental trophoblasts. Placenta 15(8):819–835

  29. 29.

    Nakao A et al (2010) Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome—an open label pilot study. J Clin Biochem Nutr 46(2):140–149

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Acknowledgments

This work was supported by National Natural Science Foundation of China (No. 81300500 to Xiang Yang).

Conflict of interest

None.

Author information

Correspondence to Xiang Yang.

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Guan, Z., Li, H., Guo, L. et al. Effects of vitamin C, vitamin E, and molecular hydrogen on the placental function in trophoblast cells. Arch Gynecol Obstet 292, 337–342 (2015). https://doi.org/10.1007/s00404-015-3647-8

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Keywords

  • Antioxidant
  • Vitamin C
  • Vitamin E
  • hCG
  • Hydrogen
  • Pregnancy
  • Placenta
  • Preeclampsia
  • TNF-a
  • Cell viability