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.
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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).
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).
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).
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).
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).
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).
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).
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).
Giess R., Tanasescu I., Steck T., Sendtner M.: Leukemia inhibitory factor gene mutations in infertile women.Mol.Human Reprod. 5, 581–586 (1999).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
McIntyre J.A.: Antiphospholipid antibodies in implantation failures.Am.J.Reprod.Immunol. 49, 221–229 (2003).
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).
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).
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).
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).
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).
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).
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).
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).
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).
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).
Ulčová-Gallová Z., Bouse V., Švábek L., Turek J., Rokyta Z.: Endometriosis in reproductive immunology.Am.J.Reprod.Immunol. 47, 269–274 (2002).
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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).
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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
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DOI: https://doi.org/10.1007/BF02932117