Natural killer cells, miscarriage, and infertility. BMJ

Department of Pathology, University of Cambridge, Cambridge CB2 1QP.
BMJ (online) (Impact Factor: 17.45). 12/2004; 329(7477):1283-5. DOI: 10.1136/bmj.329.7477.1283
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Available from: Ashley Moffett, Oct 04, 2015
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    • "It may be assumed that in favorable immune phenotype the function of immune system improves as a whole, i.e., the processes of migration of immunocompetent cells are more correct in both their quantity and quality, especially those of natural killers, into organs of the reproductive system on the basis of optimized cytokine regulation that creates optimal conditions for relatively autonomic regulation in the reproductive system. Phenotypically and functionally decidual NK cells are different from NK cells in peripheral blood and may be regarded as a separate lymphoid subset [30]. Migration of peripheral NK cells through the human endothelial and stromal decidual cells is possible because of chemokines support [31]. "
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    ABSTRACT: Immune markers that may predict IVF failure and successful implantation and pregnancy were studied. Favorable immune parameters were selected based on 90% of data of women who got pregnant and had uneventful pregnancy course and outcome in present IVF cycle. Immune phenotype and NK cell activity of peripheral blood of 123 women with multiple IVF failure were studied by flow cytometry. Some parameters that were out of favorable borders (elevated expression of CD56, CD158a in T lymphocytes, decreased levels of CD4 T lymphocytes, up-regulated expression of HLA DR in CD8+ T cells and NK cells, elevated number of NK cells and increased NK cytotoxicity, increased and decreased expression of CD158a and CD8 in NK cells) were considered to be immune deviations (ID) potentially predictive for IVF failure. In women with 0-1 ID implantation rate (IR) was 50.9% (27/53), with two ID - 42.8% (12/28), with three and more ID - 21.4% (9/42). IR in group with three ID was lower than in group with 0-1 ID (p<0.01, OR=3.8, CI: 1.52-9.48) and in group with two ID (p<0.05). Live birth rate (LBR) in women with 0-1 ID was 33.9%, with two ID - 28.5%, with three and more ID - 9.5%. LBR in group with three ID was lower than in group with 0-1 ID (p<0.01, OR=4.8, CI: 1.52-15.8) and in group with two ID (p<0.05). The absence or single ID seems to be more favorable for successful IVF program. Combination of ID may predict implantation failure to a greater degree than isolated ID. Multiple immune deviations form unfavorable "immune phenotype" for implantation and pregnancy development. Copyright © 2014. Published by Elsevier B.V. KEYWORDS: Favorable immune phenotype; IVF; Implantation; Pregnancy
    Immunology Letters 10/2014; 162(2). DOI:10.1016/j.imlet.2014.10.022 · 2.51 Impact Factor
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    • "Phenotypically and functionally different from peripheral NK cells, these cells are crucial in the establishment and maintenance of early pregnancy [2]. They become abundant in the human uterus 3–5 days post ovulation and by late secretory phase account for at least 30% of the endometrial stroma [41]. Human in vitro studies provide evidence for the ability of uNK cells to promote placental vascular growth and decidualization via production of chemokines and angiogenic factors [2]. "
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    ABSTRACT: Abnormal endometrial function remains a significant cause of implantation failure, recurrent pregnancy loss, and other pathologies responsible for female infertility. The development of novel therapies to treat infertility due to endometrial dysfunction requires an understanding of the latest advancements in endometrial cell biology, such as the role of endometrial stem cells. The remarkable regenerative capacity of the human endometrium is absolutely essential for successful reproduction and likely requires a population of stem cells in the endometrium. The purpose of this review is to provide an introduction to some of the newest concepts in endometrial stem cell biology.
    Obstetrics and Gynecology International 01/2012; 2012:851367. DOI:10.1155/2012/851367
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    • "As mentioned, during normal pregnancy, uterine NK cells are not directed to kill trophoblast cells, but in case of excessive Th1 response due to infection or inflammation, these cells become hyperactivated and potentially cytotoxic (Figure 1-I(B)) [30, 74]. Nakashima et al. [73] have shown that granulysin contributes to apoptosis of extravillous trophoblast cells in spontaneous abortions. "
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    ABSTRACT: During mammal pregnancy, a sensitive balance between hormones, cytokines, humoral factors, and local cellular interactions must be established. Cytotoxic cells infiltrating the decidua are heavily equipped with cytolytic molecules, in particular perforin and granulysin. Granulysin is especially abundant in NK cells which are able to spontaneously secrete high quantities of granulysin. Besides being a potent bactericidal and tumoricidal molecule, granulysin is also found to be a chemoattractant and a proinflammatory molecule. The precise role(s) of granulysin at the maternal-fetal interface has not been elucidated yet. It is possible that it behaves as a double-edged sword simultaneously acting as an immunomodulatory and a host defense molecule protecting both the mother and the fetus from a wide spectrum of pathogens, and on the other hand, in case of an NK cell activation, acting as an effector molecule causing the apoptosis of semiallograft trophoblast cells and consequently leading to various pregnancy disorders or pregnancy loss.
    Clinical and Developmental Immunology 01/2012; 2012(1740-2522):180272. DOI:10.1155/2012/180272 · 2.93 Impact Factor
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