Skip to main content
Log in

Association of the leukemia inhibitory factor gene mutation and the antiphospholipid antibodies in the peripheral blood of infertile women

  • Published:
Folia Microbiologica Aims and scope Submit manuscript

Abstract

To characterize the impact of the potentially functional mutation — the G to A transition at the position 3400 of the leukemia inhibitory factor (LIF; a pluripotent cytokine that plays a central role in the control of the embryo implantation) gene that leads to the exchange of valine with methionine at codon 64 we evaluated the association of the LIF gene mutation and the levels of antiphospolipid antibodies (aPLs) in the peripheral blood of infertile women (the aPLs examination was part of our routine immunological test during the infertility check-up). Eight infertile mutation-positive women were diagnosed with idiopathic infertility (n=5) and endometriosis (n=3) and their levels of aPLs in serum were compared with 115 infertile women without any LIF gene mutation. Enzyme-linked immunosorbent assay was used for the detection of seven antiphospholipid antibodies; the results were statistically assessed by the Fisher’s 2 by 2 exact test to evaluate the association of the LIF gene mutations and aPLs in serum of infertile patients. The presence of aPLs was significantly higher in our study group (100 %) than in 30 % of aPLs-positives in control infertile patients (p=0.0035) which indicates that the aPLs are elevated in women with LIF gene mutations.

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.

Similar content being viewed by others

Abbreviations

aPLs:

antiphospholipid antibodies

ELISA:

enzyme-linked immunosorbent assay

FCS:

fetal calf serum

IVF:

in vitro fertilization

LIF:

leukemia inhibitory factor

LIFR:

LIF receptor

NK:

natural killer (cells)

ph-Ser:

l-phosphatidyl-serine

SD:

standard deviation

TGGE:

temperature gradient gel electrophoresis

References

  • Aghajanova L.: Leukemia inhibitory factor and human embryo implantation.Ann.N.Y.Acad.Sci. 1034, 176–183 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Aron A.L., Gharavi A.E., Shoenfeld Y.: Mechanisms of action of antiphospholipid antibodies in the antiphospholipid syndrome.Internat.Arch.Allergy Immunol. 106, 8–12 (1995).

    CAS  Google Scholar 

  • Balasch J., Creus M., Fabregues F., Reverter J.C., Carmona F., Tassies D., Font J., Vanrell J.A.: Antiphospholipid antibodies and human reproductive failure.Human Reprod. 11, 2310–2315 (1996).

    CAS  Google Scholar 

  • Beer A.E., Kwak J.Y., Ruiz J.E.: Immunophenotypic profiles of peripheral blood lymphocytes in women with recurrent pregnancy losses and in infertile women with multiple failedin vitro fertilization cycles.Am.J.Reprod.Immunol. 35, 376–382 (1996).

    PubMed  CAS  Google Scholar 

  • Beranova M., Oliveira L.M., Bedecarrats G.Y., Schipani E., Vallejo M., Ammini A.C., Quintos J.B., Hall J.E., Martin K.A., Hayes F.J., Pitteloud N., Kaiser U.B., Crowley W.F. Jr.,Seminara S.B.: Prevalence, phenotypic spectrum, and modes of inheritance of gonadotropin-releasing hormone receptor mutations in idiopathic hypogonadotropic hypogonadism.J.Clin.Endocrinol.Metab. 86, 1580–1588 (2001).

    Article  PubMed  CAS  Google Scholar 

  • Coulam C.B., Kaider B.D., Kaider A.S., Janowicz P., Roussev R.G.: Antiphospholipid antibodies associated with implantation failure after IVF/ET.J.Assist.Reprod.Genet. 14, 603–608 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Coulam C.B., Roussev R.G.: Correlation of NK cell activation and inhibition markers with NK cytoxicity among women experiencing immunologic implantation failure afterin vitro fertilization and embryo transfer.J.Assist.Reprod.Genet. 20, 58–62 (2003).

    Article  PubMed  Google Scholar 

  • Eldar-Geva T., Wood C., Lolatgis N., Rombauts L., Kovacs G., Fuscaldo J., Trounson A.O.: Cumulative pregnancy and live birth rates in women with antiphospholipid antibodies undergoing assisted reproduction.Human Reprod. 14, 1461–1466 (1999).

    Article  CAS  Google Scholar 

  • Giess R., Tanasescu I., Steck T., Sendtner M.: Leukemia inhibitory factor gene mutations in infertile women.Mol.Human Reprod. 5, 581–586 (1999).

    Article  CAS  Google Scholar 

  • Jokhi P.P., King A., Sharkey A.M., Smith S.K., Loke Y.W.: Screening for cytokine messenger ribonucleic acids in purified human decidual lymphocyte populations by the reverse-transcriptase polymerase chain reaction.J.Immunol. 153, 4427–4435 (1994).

    PubMed  CAS  Google Scholar 

  • Kaider A.S., Kaider B.D., Janowicz P.B., Roussev R.G.: Immunodiagnostic evaluation in women with reproductive failure.Am.J.Reprod.Immunol. 42, 335–346 (1999).

    PubMed  CAS  Google Scholar 

  • Klentzeris L.D., Bulmer J.N., Warren M.A., Morrison L., Li T.C., Cooke I.D.: Lymphoid tissue in the endometrium of women with unexplained infertility: morphometric and immunohistochemical aspects.Human Reprod. 9, 646–652 (1994).

    CAS  Google Scholar 

  • Kowalik A., Vichnin M., Liu H.C., Branch W., Berkeley A.S.: Midfollicular anticardiolipin and antiphosphatidylserine antibody titers do not correlate within vitro fertilization outcome.Fertil.Steril. 68, 298–304 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Králíčková M., Šíma P., Rokyta Z.: Role of the leukemia-inhibitory factor gene mutations in infertile women: the embryo-endometrial cytokine cross talk during implantation — a delicate homeostatic equilibrium.Folia Microbiol. 50, 179–186 (2005).

    Article  Google Scholar 

  • Králíčková M., Šíma R., Vaněček T., Šíma P., Rokyta Z., Ulčová-Gallová Z., Suchá R., Uher P., Hes O.: Leukemia inhibitory factor gene mutations in the population of infertile women are not restricted to nulligravid patients.Eur.J.Obstet.Gynecol.Reprod.Biol. 127, 231–235 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Kubrycht J., Malíková P., Huan N.H., Fišerová A., Bezouška K., Kružík P., Stajner K., Moravec V., Pospíšil M.: Peripheral membrane molecules of leukocytes and NK cytotoxicity.Folia Microbiol. 38, 421–431 (1993).

    Article  CAS  Google Scholar 

  • Kwak J.Y., Beaman K.D., Gilman-Sachs A., Ruiz J.E., Schewitz D., Beer A.E.: Up-regulated expression of CD56+, CD56+/CD16+, and CD19+ cells in peripheral blood lymphocytes in pregnant women with recurrent pregnancy losses.Am.J.Reprod.Immunol. 34, 93–99 (1995).

    PubMed  CAS  Google Scholar 

  • Lukassen H.G., van der Meer A., van Lierop M.J., Lindeman E.J., Joosten I., Braat D.D.: The proportion of follicular fluid CD16+ CD56 DIM NK cells is increased in IVF patients with idiopathic infertility.J.Reprod.Immunol. 60, 71–84 (2003).

    Article  PubMed  Google Scholar 

  • Matsubayashi H., Hosaka T., Sugiyama Y., Suzuki T., Arai T., Kondo A., Sugi T., Izumi S., Makino T.: Increased natural killercell activity is associated with infertile women.Am.J.Reprod.Immunol. 46, 318–322 (2001).

    Article  PubMed  CAS  Google Scholar 

  • McIntyre J.A.: Antiphospholipid antibodies in implantation failures.Am.J.Reprod.Immunol. 49, 221–229 (2003).

    Article  PubMed  CAS  Google Scholar 

  • Michou V.I., Kanavaros P., Athanassiou V., Chronis G.B., Stabamas S., Tsilivakos V.: Fraction of the peripheral blood concentration of CD56+/CD16/CD3 cells in total natural killer cells as an indication of fertility and infertility.Fertil.Steril. 80 (Suppl. 2), 691–697 (2003).

    Article  PubMed  Google Scholar 

  • Nakamura Y., Fujino Y., Ozaki K., Ueda K., Ozaki A., Itoh F., Ogita S.: Suppression of natural killer cell activity and interleukin-2 concentration of serum obtained fromin vitro fertilization-embryo transfer patients.Am.J.Reprod.Immunol. 40, 9–12 (1998).

    PubMed  CAS  Google Scholar 

  • Ntrivalas E.I., Kwak-Kim J.Y., Gilman-Sachs A., Chung-Bang H., Ng S.C., Beaman K.D., Mantouvalos H.P., Beer A.E.: Status of peripheral blood natural killer cells in women with recurrent spontaneous abortions and infertility of unknown etiology.Human Reprod. 16, 855–861 (2001).

    Article  CAS  Google Scholar 

  • Roussev R.G., Kaider B.D., Price D.E., Coulam C.B.: Laboratory evaluation of women experiencing reproductive failure.Am.J.Reprod.Immunol. 35, 415–420 (1996).

    PubMed  CAS  Google Scholar 

  • Saito S., Nishikawa K., Morii T., Enomoto M., Narita N., Motoyoshi K., Ichijo M.: Cytokine production by CD16 CD56bright natural killer cells in the human early pregnancy decidua.Internat.Immunol. 5, 559–563 (1993).

    Article  CAS  Google Scholar 

  • Schofield G., Kimber S.J.: Leukocyte subpopulations in the uteri of leukemia inhibitory factor knockout mice during early pregnancy.Biol.Reprod. 72, 872–878 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Sher G., Fisch J.D., Maassarani G., Matzner W., Ching W., Chong P.: Antibodies to phosphatidylethanolamine and phosphatidylserine are associated with increased natural killer cell activity in non-male factor infertility patients.Human Reprod. 15, 1932–1936 (2000).

    Article  CAS  Google Scholar 

  • Steck T., Giess R., Suetterlin M.W., Bolland M., Wiest S., Poehls U.G., Dietl J.: Leukemia inhibitory factor (LIF) gene mutations in women with unexplained infertility and recurrent failure of implantation after IVF and embryo transfer.Eur.J.Obstet.Gynecol.Reprod.Biol. 112, 69–73 (2004).

    Article  PubMed  CAS  Google Scholar 

  • Ulčová-Gallová Z., Krauz V., Bouse V., Novotný Z., Rokyta Z., Fialová P., Vondráček J.: Correlation between peritoneal fluid and serum antiphospholipid antibodies in women with primary infertility.Internat.J.Fertil.Womens Med. 43, 267–272 (1998).

    Google Scholar 

  • Ulčová-Gallová Z., Novotný Z., Bouse V., Švábek L., Rokyta Z., Hradecký L., Knaizl Z., Fialová P.: Immunologic factors in the serum and peritoneal fluid in women after laparoscopy. Nonspecific factors.Česká Gynekol. 61, 23–27 (1996).

    PubMed  Google Scholar 

  • Ulčová-Gallová Z., Bouse V., Švábek L., Turek J., Rokyta Z.: Endometriosis in reproductive immunology.Am.J.Reprod.Immunol. 47, 269–274 (2002).

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M. Králíčková.

Additional information

This study was supported by theGrant Agency of the Czech Republic (grant no. 301/05/0078; M. Králíčková), by theInstitutional Research Concept of theMinistry of Education, Youth and Sports of the Czech Republic (MŠM 0021620812; Z. Ulčová-Gallová) and theInstitutional Research Concept of theInstitute of Microbiology, Academy of Sciences of the Czech Republic (AV 0Z 50200510; P. Šíma).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Králíčková, M., Ulčová-Gallová, Z., Šíma, R. et al. Association of the leukemia inhibitory factor gene mutation and the antiphospholipid antibodies in the peripheral blood of infertile women. Folia Microbiol 52, 543–548 (2007). https://doi.org/10.1007/BF02932117

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02932117

Keywords

Navigation