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An immunosupressive protein supporting embryonic implantation and having an important role in cell proliferation: The Early Pregnancy Factor

Year 2013, Volume: 3 Issue: 3, 157 - 164, 01.09.2013
https://doi.org/10.5505/sakaryamj.2013.37928

Abstract

Early pregnancy factor (EPF), identified as an immunosuppresive protein, can be detected in maternal serum within 6-24 hours of fertilization and is present for at least the first two trimester of pregnancy. Besides pregnancy, EPF is secreted by tumor cells, normal growing cells and active platelets during cell growth and division. It is also required for tumor proliferation and tissue renewal. Seventy per cent of the amino acid sequence of EPF derived from human platelets was determined and except from a single residue, it was identical to the sequence of rat mitochondrial chaperonin 10 (cpn 10). The molecular weight of the protein was found to be 10,843 Da. Whether EPF and cpn 10 are the same molecule or not is still discussed by many researchers. The rosette inhibition test (RIT) which is the most widely used and most reliable assay for EPF detection is not practical for routine utilization since it is laborious, time consuming and sensitive. Recently, it is expected to speed up the EPF studies by investigating novel assay systems that will be more practical than RIT.

References

  • Morton H, Hegh V, Clunie GJA. Immunosuppression detected in pregnant mice by rosette inhibition test. Nature 1974; 249:459- 460.
  • Athanasas-Platsis S, Quinn KA, Wong TY, Rolfe BE, Cavanagh AC, Morton H. Passive immunization of pregnant mice against early pregnancy factor causes loss of embryonic viability. J Reprod Fertil 1989; Nov;87(2):495-502.
  • Jia H, Halilou AI, Hu L, Cai W, Liu J, Huang B. Heat shock protein 10 (Hsp10) in immune-related diseases: one coin, two sides. Int J Biochem Mol Biol 2011; 2(1):47-57.
  • Morton H. Early pregnancy factor: an extracellular chaperonin 10 homologue. Immunol Cell Biol 1998; 76(6):483-96.
  • Morton H, Rolfe BE, Cavanagh AC. Ovum factor and early pregnancy factor. Curr Top Dev Biol 1987; 23:73-92.
  • Cavanagh AC. Identification of early pregnancy factor as chaperonin 10: implications for understanding its role. Rev Reprod 1996; 1(1):28-32.
  • Athanasas-Platsis S, Morton H, Dunglison GF, Kaye PL. Antibodies to early pregnancy factor retard embryonic development in mice in vivo. J Reprod Fertil 1991; 92(2):443-51.
  • Athanasas-Platsis S, Corcoran CM, Kaye PL, Cavanagh AC, Morton H. Early Pregnancy Factor is Required at Two Important Stages of Embryonic Development in the Mouse. Am J Reprod Immunol 2000; 43(4):223-33.
  • Shahani SK, Moniz CL, Gokral JS, Meherji PK. Early pregnancy factor (EPF) as a marker for detecting subclinical embryonic loss in clomiphene citrate-treated women. Am J Reprod Immunol 1995; 33:350–353.
  • Grossoa MC, Bellingeri RV, Schadeb R, Viva AB. Neutralization of early pregnancy factor by passive immunization alters normal embryonic development and cytokine balance. Inmunologia 2012; 31(4):106-114.
  • Rolfe BE, Morton H, Cavanagh AC, Detection of an early pregnancy factor like substance in sera of patients with testicular germ cell tumors. Am J Reprod Immunol 1983;3(2):97-100.
  • Mehta AR, Shahani SK. Detection of an early pregnancy factor like activity in women with gestational trophoblastic tumors. Am J Reprod Immunol Microbiol 1987;14(3):67-9.
  • Quinn KA, Athanasas-Platsis S, Wong TY, Rolfe BE, Cavanagh AC, Morton H. Monoclonal antibodies to early pregnancy factor perturb tumour cell growth. Clin Exp Immunol 1990;80(1):100-8.
  • Quinn KA, Morton H. Effect of monoclonal antibodies to early pregnancy factor (EPF) on the in vivo growth of transplantable murine tumours. Cancer Immunol Immunother 1992;34(4):265- 71.
  • Quinn KA. Early pregnancy factor: a novel factor involved in cellular proliferation. Phd thesis. University of Queensland, Brisbane, Queensland, Australia. 1991.
  • Quinn KA, Cavanagh AC, Hillyard NC, McKay DA, Morton H. Early pregnancy factor in liver regeneration after partial hepatectomy in rats: Relationship with chaperonin 10. Hepatology 1994;20(5):1294-302.
  • Ito K, Ikemizu Y, Takahashi J, Yasuda Y, Kawahata K, Goto T. Early pregnancy factor: EPF-like substances purified from pregnant bovine ovary and in vitro fertilized ovum culture medium. J Reprod Dev 1995;41(1): 85-92.
  • Corrao S, Campanella C, Anzalone R, Farina F, Zummo G, Conway de Macario E, et al. Human Hsp10 and Early Pregnancy Factor (EPF) and their relationship and involvement in cancer and immunity: Current knowledge and perspectives. Life Sci 2010;86(5-6):145-52.
  • Ikemizu Y, Yamazaki S, Takahashi J, Yasuda Y. Isolation and purification of early pregnancy factor EPF in rat serum. J Reprod Dev 1996; 42(1): 41-45
  • Cavanagh AC. Production in vitro of mouse early pregnancy factor and purification to homogeneity. J Reprod Fertil 1984;71(2):581- 92.
  • Wilson S, McCarthy R, Clarke F. In search of early pregnancy factor: Isolation of active polypeptides from pregnant ewes’ sera. J Reprod Immunol 1983;5(5):275-86.
  • Ito K, Yamamoto, Takahashi J, Yasuda Y. Purification of early pregnancy factor from cattle sera. Anim Sci Technol 1992;63:394- 397.
  • Mehta AR, Eessalu TE, Aggarwal BB. Purification and characterization of early pregnancy factor from human pregnancy serum. J Biol Chem 1989;264(4):2266-71.
  • Sueoka K, Dharmarajan AM, Miyazaki T, Atlas SJ, Wallach EE. In vivo and in vitro determination of components of rabbit early pregnancy factors. J Reprod Fertil 1989;87(1):47-53.
  • Cavanagh AC, Morton H.The purification of early-pregnancy factor to homogeneity from human platelets and identification as chaperonin 10. Eur J Biochem 1994;222(2):551-60.
  • Summers KM, Murphy RM, Webb GC, Peters GB, Morton H, Cassady AI. The Human Early Pregnancy Factor/Chaperonin 10 Gene Family. Biochem Mol Med 1996;58(1):52-8.
  • Bach JF, Antoine B In vitro detection of immunosuppressive activity of antilymphocyte sera. Nature 1968; 217 658-659.
  • Morton H. Early Pregnancy Factor (EPF): a Link between Fertilization and Immunomodulation. Aust J Biol Sci 1984;37(5- 6):393-407.
  • Rolfe BE, Morton H, Clarke FM. Early Pregnancy Factor is an immunosuppresive contaminant of commercial preparations of human chorionic gonadotrophin. Clin Exp Immunol 1983;51(1):45- 52.
  • Ball BA, Little TV, Hillman RB, Woods GL. Pregnancy rates at Days 2 and 14 and estimated embryonic loss rates prior to Day 14 in normal and subfertile mares. Theriogenology 1986; 26:611- 619.
  • Takagi M, Nishimura K, Oguri N, Ohnuma K, Ito K, Takahashi J, et al. Measurement of early pregnancy factor activity for monitoring the viability of the equine embryo. Theriogenology 1998;50(2):255-62.
  • Knotek Z. Demonstration of Early Pregnancy Factor in Gilts During the Reproductive Cycle. Acta Vet Brno 1990, 59: 35-40 .
  • Morton H, Morton DJ, Ellendorff F. The appearance and characteristics of early pregnancy factor in the pig. J Reprod Fertil 1983;69(2):437-46.
  • Sakonju I, Enomoto S, Kamimura S, Hamana K. Monitoring bovine emryo viability with early pregnancy Factor. J Vet Med Sci 1993;55(2):271-4.
  • Ohnuma K, Ito K, Takahashi J, Nambo Y, Miyake Y. Partial purification of mare early pregnancy factor. AJRI 2004; 51:95–101
  • Mavedati O, Rastegarnia A, Habibian R, Bari YN, Bandarian E. Early Pregnancy Diagnosis in Water Buffalo by Early Pregnancy Factor Measurement Using Rosette Inhibition Test. Global Veterinaria 2013;10(4): 391-393
  • Lash GE, Legge M, Fisher M. Synthesis of Early Pregnancy Factor Using Red Deer (Cervus elaphus) as a Delayed Implantation Model. J Assist Reprod Genet 1997;14(1):39-43.
  • Cruz YP, Selwood L, Morton H, Cavanagh AC. Significance of serum early pregnancy factor concentrations during pregnancy and embryonic development in Sminthopsis macroura (Spencer) (Marsupialia: Dasyuridae). Reproduction 2001;121(6):933-9.

Embriyo implantasyonunu destekleyen ve hücre proliferasyonunda önemli rol oynayan immunosupresif bir protein: Erken Gebelik Faktörü

Year 2013, Volume: 3 Issue: 3, 157 - 164, 01.09.2013
https://doi.org/10.5505/sakaryamj.2013.37928

Abstract

İmmunosupresif özelliğe sahip bir protein olan erken gebelik faktörü (EGF) fertilizasyondan sonra yaklaşık 6-24 saat içerisinde maternal serumda tespit edilebilir ve pek çok canlı türünde gebeliğin ilk iki trimesteri boyunca üretilir. EGF'nin önemi sadece gebelik süreciyle sınırlı değildir. Yapılan çalışmalar EGF'nin tümör hücreleri, normal çoğalan hücreler ve aktif plateletler tarafından hücre büyümesi ve bölünmesi sırasında üretildiğini, tümör hücrelerinin proliferasyonu ve doku yenilenmesi için de gerekli olduğunu göstermiştir. İnsan plateletinden izole edilen ve moleküler ağırlığı 10,843 Da olarak bulunan EGF'nin amino asit sıralamasının yüzde yetmişi belirlenmiş ve tek bir amino asit rezidüsü dışında sıçan mitokondriyal şaperon 10 (cpn 10) ile aynı olduğu tespit edilmiştir. EGF ile cpn 10'un aynı molekül olup olmadığı tartışmaları ise halen devam etmektedir. EGF tespitinde en çok kullanılan ve aynı zamanda en güvenilir test olan "rozet inhibisyon testi" (RIT) zahmetli, zaman alıcı ve hassas olması sebebiyle rutin kullanımda pratik olmamaktadır. Son yıllarda yapılan çalışmalarda EGF aktivitesini ölçmek için RIT'a alternatif yeni yöntemlerin araştırılmasıyla birlikte bu alanda yapılacak çalışmalara hız kazandırılması amaçlanmaktadır.

References

  • Morton H, Hegh V, Clunie GJA. Immunosuppression detected in pregnant mice by rosette inhibition test. Nature 1974; 249:459- 460.
  • Athanasas-Platsis S, Quinn KA, Wong TY, Rolfe BE, Cavanagh AC, Morton H. Passive immunization of pregnant mice against early pregnancy factor causes loss of embryonic viability. J Reprod Fertil 1989; Nov;87(2):495-502.
  • Jia H, Halilou AI, Hu L, Cai W, Liu J, Huang B. Heat shock protein 10 (Hsp10) in immune-related diseases: one coin, two sides. Int J Biochem Mol Biol 2011; 2(1):47-57.
  • Morton H. Early pregnancy factor: an extracellular chaperonin 10 homologue. Immunol Cell Biol 1998; 76(6):483-96.
  • Morton H, Rolfe BE, Cavanagh AC. Ovum factor and early pregnancy factor. Curr Top Dev Biol 1987; 23:73-92.
  • Cavanagh AC. Identification of early pregnancy factor as chaperonin 10: implications for understanding its role. Rev Reprod 1996; 1(1):28-32.
  • Athanasas-Platsis S, Morton H, Dunglison GF, Kaye PL. Antibodies to early pregnancy factor retard embryonic development in mice in vivo. J Reprod Fertil 1991; 92(2):443-51.
  • Athanasas-Platsis S, Corcoran CM, Kaye PL, Cavanagh AC, Morton H. Early Pregnancy Factor is Required at Two Important Stages of Embryonic Development in the Mouse. Am J Reprod Immunol 2000; 43(4):223-33.
  • Shahani SK, Moniz CL, Gokral JS, Meherji PK. Early pregnancy factor (EPF) as a marker for detecting subclinical embryonic loss in clomiphene citrate-treated women. Am J Reprod Immunol 1995; 33:350–353.
  • Grossoa MC, Bellingeri RV, Schadeb R, Viva AB. Neutralization of early pregnancy factor by passive immunization alters normal embryonic development and cytokine balance. Inmunologia 2012; 31(4):106-114.
  • Rolfe BE, Morton H, Cavanagh AC, Detection of an early pregnancy factor like substance in sera of patients with testicular germ cell tumors. Am J Reprod Immunol 1983;3(2):97-100.
  • Mehta AR, Shahani SK. Detection of an early pregnancy factor like activity in women with gestational trophoblastic tumors. Am J Reprod Immunol Microbiol 1987;14(3):67-9.
  • Quinn KA, Athanasas-Platsis S, Wong TY, Rolfe BE, Cavanagh AC, Morton H. Monoclonal antibodies to early pregnancy factor perturb tumour cell growth. Clin Exp Immunol 1990;80(1):100-8.
  • Quinn KA, Morton H. Effect of monoclonal antibodies to early pregnancy factor (EPF) on the in vivo growth of transplantable murine tumours. Cancer Immunol Immunother 1992;34(4):265- 71.
  • Quinn KA. Early pregnancy factor: a novel factor involved in cellular proliferation. Phd thesis. University of Queensland, Brisbane, Queensland, Australia. 1991.
  • Quinn KA, Cavanagh AC, Hillyard NC, McKay DA, Morton H. Early pregnancy factor in liver regeneration after partial hepatectomy in rats: Relationship with chaperonin 10. Hepatology 1994;20(5):1294-302.
  • Ito K, Ikemizu Y, Takahashi J, Yasuda Y, Kawahata K, Goto T. Early pregnancy factor: EPF-like substances purified from pregnant bovine ovary and in vitro fertilized ovum culture medium. J Reprod Dev 1995;41(1): 85-92.
  • Corrao S, Campanella C, Anzalone R, Farina F, Zummo G, Conway de Macario E, et al. Human Hsp10 and Early Pregnancy Factor (EPF) and their relationship and involvement in cancer and immunity: Current knowledge and perspectives. Life Sci 2010;86(5-6):145-52.
  • Ikemizu Y, Yamazaki S, Takahashi J, Yasuda Y. Isolation and purification of early pregnancy factor EPF in rat serum. J Reprod Dev 1996; 42(1): 41-45
  • Cavanagh AC. Production in vitro of mouse early pregnancy factor and purification to homogeneity. J Reprod Fertil 1984;71(2):581- 92.
  • Wilson S, McCarthy R, Clarke F. In search of early pregnancy factor: Isolation of active polypeptides from pregnant ewes’ sera. J Reprod Immunol 1983;5(5):275-86.
  • Ito K, Yamamoto, Takahashi J, Yasuda Y. Purification of early pregnancy factor from cattle sera. Anim Sci Technol 1992;63:394- 397.
  • Mehta AR, Eessalu TE, Aggarwal BB. Purification and characterization of early pregnancy factor from human pregnancy serum. J Biol Chem 1989;264(4):2266-71.
  • Sueoka K, Dharmarajan AM, Miyazaki T, Atlas SJ, Wallach EE. In vivo and in vitro determination of components of rabbit early pregnancy factors. J Reprod Fertil 1989;87(1):47-53.
  • Cavanagh AC, Morton H.The purification of early-pregnancy factor to homogeneity from human platelets and identification as chaperonin 10. Eur J Biochem 1994;222(2):551-60.
  • Summers KM, Murphy RM, Webb GC, Peters GB, Morton H, Cassady AI. The Human Early Pregnancy Factor/Chaperonin 10 Gene Family. Biochem Mol Med 1996;58(1):52-8.
  • Bach JF, Antoine B In vitro detection of immunosuppressive activity of antilymphocyte sera. Nature 1968; 217 658-659.
  • Morton H. Early Pregnancy Factor (EPF): a Link between Fertilization and Immunomodulation. Aust J Biol Sci 1984;37(5- 6):393-407.
  • Rolfe BE, Morton H, Clarke FM. Early Pregnancy Factor is an immunosuppresive contaminant of commercial preparations of human chorionic gonadotrophin. Clin Exp Immunol 1983;51(1):45- 52.
  • Ball BA, Little TV, Hillman RB, Woods GL. Pregnancy rates at Days 2 and 14 and estimated embryonic loss rates prior to Day 14 in normal and subfertile mares. Theriogenology 1986; 26:611- 619.
  • Takagi M, Nishimura K, Oguri N, Ohnuma K, Ito K, Takahashi J, et al. Measurement of early pregnancy factor activity for monitoring the viability of the equine embryo. Theriogenology 1998;50(2):255-62.
  • Knotek Z. Demonstration of Early Pregnancy Factor in Gilts During the Reproductive Cycle. Acta Vet Brno 1990, 59: 35-40 .
  • Morton H, Morton DJ, Ellendorff F. The appearance and characteristics of early pregnancy factor in the pig. J Reprod Fertil 1983;69(2):437-46.
  • Sakonju I, Enomoto S, Kamimura S, Hamana K. Monitoring bovine emryo viability with early pregnancy Factor. J Vet Med Sci 1993;55(2):271-4.
  • Ohnuma K, Ito K, Takahashi J, Nambo Y, Miyake Y. Partial purification of mare early pregnancy factor. AJRI 2004; 51:95–101
  • Mavedati O, Rastegarnia A, Habibian R, Bari YN, Bandarian E. Early Pregnancy Diagnosis in Water Buffalo by Early Pregnancy Factor Measurement Using Rosette Inhibition Test. Global Veterinaria 2013;10(4): 391-393
  • Lash GE, Legge M, Fisher M. Synthesis of Early Pregnancy Factor Using Red Deer (Cervus elaphus) as a Delayed Implantation Model. J Assist Reprod Genet 1997;14(1):39-43.
  • Cruz YP, Selwood L, Morton H, Cavanagh AC. Significance of serum early pregnancy factor concentrations during pregnancy and embryonic development in Sminthopsis macroura (Spencer) (Marsupialia: Dasyuridae). Reproduction 2001;121(6):933-9.
There are 38 citations in total.

Details

Primary Language Turkish
Journal Section Articles
Authors

Elvan Özbek This is me

Nureddin Cengiz This is me

Sevinç Yanar

Publication Date September 1, 2013
Submission Date September 7, 2015
Published in Issue Year 2013 Volume: 3 Issue: 3

Cite

AMA Özbek E, Cengiz N, Yanar S. Embriyo implantasyonunu destekleyen ve hücre proliferasyonunda önemli rol oynayan immunosupresif bir protein: Erken Gebelik Faktörü. Sakarya Tıp Dergisi. September 2013;3(3):157-164. doi:10.5505/sakaryamj.2013.37928

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