The impact of plasma SOCS3 levels and endometrial leukocytes on unexplained infertility

The impact of plasma SOCS3 levels and endometrial leukocytes on unexplained infertility

Background/aim: To investigate the possible differences in endometrial leukocyte subtype distribution between women withunexplained infertility and normal fertile women and to determine whether there is a correlation between endometrial leukocyte countsand plasma cytokine levels in unexplained infertility.Materials and methods: This case-control study involved 79 infertile and 40 fertile women. Peripheral venous blood samples andendometrial samples were obtained on day 21 of the menstrual cycle. Plasma interleukin-4 (IL4), IL6, IL10, IL17, IL35, interferongamma(IFN-g), tumor necrosis factor-alpha (TNF-a), transforming growth factor-beta (TGF-b), and suppressor of cytokine signaling-3(SOCS3) levels were determined by enzyme-linked immunosorbent assay. Endometrial CD8, CD56, and CD163 counts were detectedby immunohistochemistry.Results: CD8 and CD56 counts were significantly higher, while CD163 count was significantly lower in infertile women than in fertilewomen. Plasma SOCS3, IL35, and IL4 levels of the infertile group were significantly lower than those of the fertile group (P < 0.01); theremaining cytokine levels were significantly higher in the infertile group than in the fertile group (P < 0.01).Conclusion: We observed aberrant cytotoxic immune activity in infertile women. The interaction between plasma SOCS3 levels andstaining degree of endometrial leukocytes may be either the reason for or result of infertility leading to unavailability of the environmentfor implantation.

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  • Rizzo R, Lo Monte G, Bortolotti D, Graziano A, Gentili V, Di Luca D, Marci R. Impact of soluble HLA-G levels and endometrial NK cells in uterine flushing samples from primary and secondary unexplained infertile women. Int J Mol Sci 2015; 16: 5510-5516.
  • Goel T, Mahey R, Bhatla N, Kalaivani M, Pant S, Kriplani A. Pregnancy after endometrial scratching in infertile couples undergoing ovulation induction and intrauterine insemination cycles-a randomized controlled trial. J Assist Reprod Genet 2017; 34: 1051-1058.
  • Nakamura H, Jasper MJ, Hull ML, Aplin JD, Robertson SA. Macrophages regulate expression of α1,2-fucosyltransferase genes in humanendometrial epithelial cells. Mol Hum Reprod 2012; 18: 204-215.
  • Clark DA, Blois S, Kandil J, Handjiski B, Manuel J, Arck PC. Reduced uterine indoleamine 2,3-dioxygenase versus increased Th1/Th2 cytokine ratios as a basis for occult and clinical pregnancy failure in mice and humans. Am J Reprod Immunol 2005; 54: 203-216.
  • Russell P, Sacks G, Tremellen K, Gee A. The distribution of immune cells and macrophages in the endometrium of women with recurrent reproductive failure. III: Further observations and reference ranges. Pathology 2013; 45: 393-401.
  • Mehta BN, Nath N, Chimote N. Periodicity in the levels of serum plasminogen activator inhibitor-1 is a robust prognostic factor for embryo implantation and clinical pregnancy in ongoing IVF cycles. J Hum Reprod Sci 2014; 7: 198-205.
  • Lee SK, Kim CJ, Kim DJ, Kang JH. Immune cells in the female reproductive tract. Immune Netw 2015; 15: 16-26.
  • Lee JY, Lee M, Lee SK. Role of endometrial immune cells in implantation. Clin Exp Reprod Med. 2011; 38: 119-125.
  • Salamonsen LA, Lathbury LJ. Endometrial leukocytes and menstruation. Hum Reprod Update 2000; 6: 16-27.
  • Wira CR, Fahey JV, Rodriguez-Garcia M, Shen Z, Patel MV. Regulation of mucosal immunity in the female reproductive tract: the role of sex hormones in immune protection against sexually transmitted pathogens. Am J Reprod Immunol 2014; 72: 236-258.
  • Lidström C, Matthiesen L, Berg G, Sharma S, Ernerudh J, Ekerfelt C. Cytokine secretion patterns of NK cells and macrophages in early human pregnancy decidua and blood: implications for suppressor macrophages in decidua. Am J Reprod Immunol 2003; 50: 444-452.
  • Yan C, Liu Y, Gao H, Wang X. Suppressors of cytokine signaling 3 is essential for FcγR-mediated inflammatory response via enhancing CCAAT/enhancer-binding protein δ transcriptional activity in macrophages. Exp Cell Res 2015; 337: 120-127.
  • Ando T, Komatsu T, Naiki Y, Yokochi T, Watanabe D, Koide N. Pretreatment of LPS inhibits IFN-β-induced STAT1 phosphorylation through SOCS3 induced by LPS. Biomed Pharmacother 2015; 76: 1-5.
  • Matteo M, Serviddio G, Massenzio F, Scillitani G, Castellana L, Picca G, Sanguedolce F, Cignarelli M, Altomare E, Bufo P et al. Reduced percentage of natural killer cells associated with impaired cytokine network in the secretory endometrium of infertile women with polycystic ovary syndrome. Fertil Steril 2010; 94: 2222-2227.
  • Lynch L, Golden-Mason L, Eogan M, O’Herlihy C, O’Farrelly C. Cells with haematopoietic stem cell phenotype in adult human endometrium: relevance to infertility? Hum Reprod 2007; 22: 919-926.
  • Zhu HX, Zhang YW, Huang LL. Effects of low dose mifepristone on population and subsets of natural killer cells in human endometrium during receptive phase. Zhonghua Fu Chan Ke Za Zhi 2007; 42: 826-829.
  • Klentzeris LD, Bulmer JN, Warren MA, Morrison L, Li TC, Cooke ID. Lymphoid tissue in the endometrium of women with unexplained infertility: morphometric and immunohistochemical aspects. Hum Reprod 1994; 9: 646-652.
  • Fukui A, Fujii S, Yamaguchi E, Kimura H, Sato S, Saito Y. Natural killer cell subpopulations and cytotoxicity for infertile patients undergoing in vitro fertilization. Am J Reprod Immunol 1999; 41: 413-422.
  • Baczkowski T, Kurzawa R. Immunophenotypic profiles of peripheral blood lymphocytes on the day of embryo transfer in women undergoing in vitro fertilization. Folia Histochem Cytobiol 2007; 45: 73-77.
  • Matsubayashi H, Shida M, Kondo A, Suzuki T, Sugi T, Izumi S, Hosaka T, Makino T. Preconception peripheral natural killer cell activity as a predictor of pregnancy outcome in patients with unexplained infertility. Am J Reprod Immunol 2005; 53: 126-131.
  • Peralta CG, Han VK, Horrocks J, Croy BA, van den Heuvel MJ. CD56bright cells increase expression of {alpha}4 integrin at ovulation in fertile cycles. J Leukoc Biol 2008; 84: 1065-1074.
  • McGrath E, Ryan EJ, Lynch L, Golden-Mason L, Mooney E, Eogan M, O’Herlihy C, O’Farrelly C. Changes in endometrial natural killer cell expression of CD94, CD158a and CD158b are associated with infertility. Am J Reprod Immunol 2009; 61: 265-276.
  • Winger EE, Reed JL, Ashoush S, El-Toukhy T, Ahuja S, Taranissi M. Degree of TNF-α/IL-10 cytokine elevation correlates with IVF success rates in women undergoing treatment with Adalimumab (Humira) and IVIG. Am J Reprod Immunol 2011; 65: 610-618.
  • Fornari MC, Sarto A, Berardi VE, Martínez MA, Rocha MG, Pasqualini S, Diez RA. Effect of ovaric hyper-stimulation on blood lymphocyte subpopulations, cytokines, leptin and nitrite among patients with unexplained infertility. Am J Reprod Immunol 2002; 48: 394-403.
  • Michimata T, Ogasawara MS, Tsuda H, Suzumori K, Aoki K, Sakai M, Fujimura M, Nagata K, Nakamura M, Saito S. Distributions of endometrial NK cells, B cells, T cells, and Th2/ Tc2 cells fail to predict pregnancy outcome following recurrent abortion. Am J Reprod Immunol 2002; 47: 196-202.
  • Galgani M, Insabato L, Calì G, Della Gatta AN, Mirra P, Papaccio F, Santopaolo M, Alviggi C, Mollo A, Strina I et al. Regulatory T cells, inflammation, and endoplasmic reticulum stress in women with defective endometrial receptivity. Fertil Steril 2015; 103: 1579-1586.
  • Carvalho AV, Reinaud P, Forde N, Healey GD, Eozenou C, Giraud-Delville C, Mansouri-Attia N, Gall L, Richard C, Lonergan P et al. SOCS genes expression during physiological and perturbed implantation in bovine endometrium. Reproduction 2014; 148: 545-557.
  • Xu X, Wang Q, Deng B, Wang H, Dong Z, Qu X, Kong B. Monocyte chemoattractant protein-1 secreted by decidual stromal cells inhibits NK cells cytotoxicity by up-regulating expression of SOCS3. PLoS One 2012; 7: 41869.
  • Braunschweig A, Poehlmann TG, Busch S, Schleussner E, Markert UR. Signal transducer and activator of transcription 3 (STAT3) and Suppressor of Cytokine Signaling (SOCS3) balance controls cytotoxicity and IL-10 expression in deciduallike natural killer cell line NK-92. Am J Reprod Immunol 2011; 66: 329-335.
Turkish Journal of Medical Sciences-Cover
  • ISSN: 1300-0144
  • Yayın Aralığı: Yılda 6 Sayı
  • Yayıncı: TÜBİTAK