Skip to main content
Log in

Insulin-like growth factor-1 protects preimplantation embryos from anti-developmental actions of menadione

  • Reproductive Toxicology
  • Published:
Archives of Toxicology Aims and scope Submit manuscript

Abstract

Menadione is a naphthoquinone used as a vitamin K source in animal feed that can generate reactive oxygen species (ROS) and cause apoptosis. Here, we examined whether menadione reduces development of preimplantation bovine embryos in a ROS-dependent process and tested the hypothesis that actions of menadione would be reduced by insulin-like growth factor-1 (IGF-1). Menadione caused a concentration-dependent decrease in the proportion of embryos that became blastocysts. All concentrations tested (1, 2.5, and 5.0 μM) inhibited development. Treatment with 100 ng/ml IGF-1 reduced the magnitude of the anti-developmental effects of the two lowest menadione concentrations. Menadione also caused a concentration-dependent increase in the percent of cells positive for the TUNEL reaction. The response was lower for IGF-1-treated embryos. The effects of menadione were mediated by ROS because (1) the anti-developmental effect of menadione was blocked by the antioxidants dithiothreitol and Trolox and (2) menadione caused an increase in ROS generation. Treatment with IGF-1 did not reduce ROS formation in menadione-treated embryos. In conclusion, concentrations of menadione as low as 1.0 μM can compromise development of bovine preimplantation embryos to the blastocyst stage of development in a ROS-dependent mechanism. Anti-developmental actions of menadione can be blocked by IGF-1 through effects downstream of ROS generation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Achanta G, Sasaki R, Feng L, Carew JS, Lu W, Pelicano H, Keating MJ, Huang P, Achanta G, Sasaki R, Feng L (2005) Novel role of p53 in maintaining mitochondrial genetic stability through interaction with DNA pol γ. EMBO J 24:3482–3492

    Article  CAS  PubMed  Google Scholar 

  • Aréchiga CF, Ealy AD, Hansen PJ (1995) Evidence that glutathione is involved in thermotolerance of preimplantation murine embryos. Biol Reprod 52:1296–1301

    Article  PubMed  Google Scholar 

  • Block J, Drost M, Monson RL, Rutledge JJ, Rivera RM, Paula-Lopes FF, Ocon OM, Krininger CE III, Liu J, Hansen PJ (2003) Use of insulin-like growth factor-I during embryo culture and treatment of recipients with gonadotropin-releasing hormone to increase pregnancy rates following the transfer of in vitro-produced embryos to heat-stressed, lactating cows. J Anim Sci 81:1590–1602

    CAS  PubMed  Google Scholar 

  • Byrne AT, Southgate J, Brison DR, Leese HJ (2002) Effects of insulin-like growth factors I and II on tumour-necrosis-factor-α-induced apoptosis in early murine embryos. Reprod Fertil Dev 14:79–83

    Article  CAS  PubMed  Google Scholar 

  • Cianfarani S, Tedeschi B, Germani D, Prete SP, Rossi P, Vernole P, Caporossi D, Boscherini B (1998) In vitro effects of growth hormone (GH) and insulin-like growth factor I and II (IGF-I and -II) on chromosome fragility and p53 protein expression in human lymphocytes. Eur J Clin Invest 28:41–47

    Article  CAS  PubMed  Google Scholar 

  • Clark MA, Perks CM, Winters ZE, Holly JM (2005) DNA damage uncouples the mitogenic response to IGF-I in MCF-7 malignant breast cancer cells by switching the roles of PI3 kinase and p21WAF1/Cip1. Int J Cancer 116:506–513

    Article  CAS  PubMed  Google Scholar 

  • Criddle DN, Gillies S, Baumgartner-Wilson HK, Jaffar M, Chinje EC, Passmore S, Chvanov M, Barrow S, Gerasimenko OV, Tepikin AV, Sutton R, Petersen OH (2006) Menadione-induced reactive oxygen species generation via redox cycling promotes apoptosis of murine pancreatic acinar cells. J Biol Chem 281:40485–40492

    Article  CAS  PubMed  Google Scholar 

  • de Castro e Paula LA, Hansen PJ (2008) Modification of actions of heat shock on development and apoptosis of cultured preimplantation bovine embryos by oxygen concentration and dithiothreitol. Mol Reprod Dev 75:1338–1350

    Article  PubMed  Google Scholar 

  • Gardiner CS, Reed DJ (1994) Status of glutathione during oxidant-induced oxidative stress in the preimplantation mouse embryo. Biol Reprod 51:1307–1314

    Article  CAS  PubMed  Google Scholar 

  • Gardiner CS, Reed DJ (1995) Synthesis of glutathione in the preimplantation mouse embryo. Arch Biochem Biophys 318:30–36

    Article  CAS  PubMed  Google Scholar 

  • Guérin P, El Mouatassimm S, Ménézo Y (2001) Oxidative stress and protection against reactive oxygen species in the pre-implantation embryo and its surroundings. Hum Reprod Update 7:175–189

    Article  PubMed  Google Scholar 

  • Guthrie HD, Welch GR, Long JA (2008) Mitochondrial function and reactive oxygen species action in relation to boar motility. Theriogenology 70:1209–1215

    Article  CAS  PubMed  Google Scholar 

  • Jousan FD, Hansen PJ (2004) Insulin-like growth factor-I as a survival factor for the bovine preimplantation embryo exposed to heat shock. Biol Reprod 71:1665–1670

    Article  CAS  PubMed  Google Scholar 

  • Jousan FD, Hansen PJ (2007) Insulin-like growth factor-I promotes resistance of bovine preimplantation embryos to heat shock through actions independent of its anti-apoptotic actions requiring PI3K signaling. Mol Reprod Dev 74:189–196

    Article  CAS  PubMed  Google Scholar 

  • Jousan FD, Oliveira LJ, Hansen PJ (2008) Short-term culture of in vitro produced bovine preimplantation embryos with insulin-like growth factor-I prevents heat shock-induced apoptosis through activation of the phosphatidylinositol 3-kinase/Akt pathway. Mol Reprod Dev 75:681–688

    Article  CAS  PubMed  Google Scholar 

  • Kurmasheva RT, Houghton PJ (2006) IGF-I mediated survival pathways in normal and malignant cells. Biochim Biophys Acta 1766:1–22

    CAS  PubMed  Google Scholar 

  • Kurzawa R, Glabowski W, Baczkowski T, Wiszniewska B, Marchlewicz M (2004) Growth factors protect in vitro cultured embryos from the consequences of oxidative stress. Zygote 12:231–240

    Article  CAS  PubMed  Google Scholar 

  • Lamson DW, Plaza SM (2003) The anticancer effects of vitamin K. Altern Med Rev 8:303–318

    PubMed  Google Scholar 

  • Lim JM, Liou SS, Hansel W (1996) Intracytoplasmic glutathione concentration and the role of β-mercaptoethanol in preimplantation development of bovine embryos. Theriogenology 46:429–439

    Article  CAS  PubMed  Google Scholar 

  • Łuczak K, Balcerczyk A, Soszyński M, Bartosz G (2004) Low concentration of oxidant and nitric oxide donors stimulate proliferation of human endothelial cells in vitro. Cell Biol Int 28:483–486

    Article  PubMed  Google Scholar 

  • Monks TJ, Hanzlik RP, Cohen GM, Ross D, Graham DG (1992) Quinone chemistry and toxicity. Toxicol Appl Pharmacol 112:2–16

    Article  CAS  PubMed  Google Scholar 

  • Orsi NM, Leese HJ (2001) Protection against reactive oxygen species during mouse preimplantation embryo development: role of EDTA, oxygen tension, catalase, superoxide dismutase and pyruvate. Mol Reprod Dev 59:44–53

    Article  CAS  PubMed  Google Scholar 

  • Osada S, Sakashita F, Hosono Y, Nonaka K, Tokuyama Y, Tanaka H, Sasaki Y, Tomita H, Komori S, Matsui S, Takahashi T (2008) Extracellular signal-regulated kinase phosphorylation due to menadione-induced arylation mediates growth inhibition of pancreas cancer cells. Cancer Chemother Pharmacol 62:315–320

    Article  CAS  PubMed  Google Scholar 

  • Oztopçu P, Kabadere S, Mercangoz A, Uyar R (2004) Comparison of vitamins K1, K2 and K3 effects on growth of rat glioma and human glioblastoma multiforme cells in vitro. Acta Neurol Belg 104:106–110

    PubMed  Google Scholar 

  • Sakatani M, Yamanaka K, Kobayashi S, Takahashi M (2008) Heat shock-derived reactive oxygen species induce embryonic mortality in in vitro early stage bovine embryos. J Reprod Dev 54:496–501

    Article  CAS  PubMed  Google Scholar 

  • Sasaki R, Suzuki Y, Yonezawa Y, Ota Y, Okamoto Y, Demizu Y, Huang P, Yoshida H, Sugimura K, Mizushina Y (2008) DNA polymerase γ inhibition by vitamin K3 induces mitochondria-mediated cytotoxicity in human cancer cells. Cancer Sci 99:1040–1048

    Article  CAS  PubMed  Google Scholar 

  • Sata N, Klonowski-Stumpe H, Han B, Häussinger D, Niederau C (1997) Menadione induces both necrosis and apoptosis in rat pancreas acinar AR4-2J cells. Free Radic Biol Med 23:844–850

    Article  CAS  PubMed  Google Scholar 

  • Sikka SC (2004) Role of oxidative stress and antioxidants in andrology and assisted reproductive technology. J Androl 25:5–18

    CAS  PubMed  Google Scholar 

  • Soto P, Natzke RP, Hansen PJ (2003) Identification of possible mediators of embryonic mortality caused by mastitis: actions of lipopolysaccharide, prostaglandin F, and the nitric oxide generator, sodium nitroprusside dehydrate, on oocyte maturation and embryonic development in cattle. Am J Reprod Immunol 50:263–272

    Article  CAS  PubMed  Google Scholar 

  • Spanos S, Becker DL, Winston RML, Hardy K (2000) Anti-apoptotic action of insulin-like growth factor-1 during human preimplantation embryo development. Biol Reprod 63:1413–1420

    Article  CAS  PubMed  Google Scholar 

  • Wang PH, Schaaf GJ, Chen WH, Feng J, Prins BA, Levin ER, Bahl JJ (1998) IGF I induction of p53 requires activation of MAP kinase in cardiac muscle cells. Biochem Biophys Res Commun 245:912–917

    Article  CAS  PubMed  Google Scholar 

  • Wochna A, Niemczyk E, Kurono C, Masaoka M, Kedzior J, Słomińska E, Lipiński M, Wakabayashi T (2007) A possible role of oxidative stress in the switch mechanism of the cell death mode from apoptosis to necrosis—studies on ρ0 cells. Mitochondrion 7:119–124

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This project was supported by National Research Initiative Competitive Grant no. 2007-35203-18073 from the USDA Cooperative State Research, Education, and Extension Service. The authors thank William Rembert, for invaluable technical assistance, Marshall, Adam, and Alex Chernin and employees of Central Beef Packing Co. (Center Hill, FL) for providing ovaries; and Scott A. Randell of Southeastern Semen Services (Wellborn, FL) for donating semen.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Peter James Hansen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Moss, J.I., Pontes, E. & Hansen, P.J. Insulin-like growth factor-1 protects preimplantation embryos from anti-developmental actions of menadione. Arch Toxicol 83, 1001–1007 (2009). https://doi.org/10.1007/s00204-009-0458-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00204-009-0458-3

Keywords

Navigation