Interventions to improve reproductive outcomes in women with elevated natural killer cells undergoing assisted reproduction techniques: a systematic review of literature

Polański, Łukasz; Barbosa, Marco Aurélio A.; Martins, Wellington P.; Baumgarten, Miriam; Campbell, B. K.; Brosens, Jan J.; Quenby, Siobhán; Raine‐Fenning, Nick

doi:10.1093/humrep/det414

Cited by 63 publications

(48 citation statements)

References 63 publications

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“…Indeed, two systematic recent reviews of the literature also caution against the use of any adjuvant therapies aimed at suppressing NK cells (107,108). Our genetic findings on KIR-HLA-C variants in preeclampsia and the other GOS must still be regarded as preliminary, as they have not been repeated by other investigators in European or other populations.…”

Section: Future Directionsmentioning

confidence: 78%

Uterine NK cells: active regulators at the maternal-fetal interface

Moffett¹,

Colucci²

2014

J. Clin. Invest.

344

301

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Pregnancy presents an immunological conundrum because two genetically different individuals coexist. The maternal lymphocytes at the uterine maternal-fetal interface that can recognize mismatched placental cells are T cells and abundant distinctive uterine NK (uNK) cells. Multiple mechanisms exist that avoid damaging T cell responses to the fetus, whereas activation of uNK cells is probably physiological. Indeed, genetic epidemiological data suggest that the variability of NK cell receptors and their MHC ligands define pregnancy success; however, exactly how uNK cells function in normal and pathological pregnancy is still unclear, and any therapies aimed at suppressing NK cells must be viewed with caution. Allorecognition of fetal placental cells by uNK cells is emerging as the key maternalfetal immune mechanism that regulates placentation. The maternal-fetal interface in the uterusThe immunological paradox of pregnancy became a central preoccupation of immunologists after the discovery of acquired immunological tolerance (1). Pregnancy and transplantation were instrumental in the discovery of MHC polymorphisms, since the best natural producers of alloantibodies against HLA molecules are multiparous women (2) and polytransfused individuals (3). Since Medawar's influential essay (4), the focus for immunologists has been how maternal T cells become tolerant of the fetal allograft. The current state of this field has been summarized in recent scholarly reviews (5, 6). We have taken a different approach that arose from studying pregnancy disorders, which affect millions of women and are a persistent global health problem. This view of the maternal immune system arose from considering how placentation evolved in mammals and is centered on the anatomy, physiology, and pathology of the pregnant uterus. We focus on the immune cells present in the pregnant uterine lining, the decidua, dominated by NK cells (known as decidual NK cells or uterine NK

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Section: Future Directionsmentioning

confidence: 78%

Uterine NK cells: active regulators at the maternal-fetal interface

Moffett¹,

Colucci²

2014

J. Clin. Invest.

344

301

View full text Add to dashboard Cite

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“…Taken together, these data may suggest that SCH may represent not only an element potentially responsible for the poor pregnancy outcome, but also a marker of preexisting immune abnormalities which can participate to the pathologic condition in a manner that they can be the cause or the consequence of a thyroid impairment. 21,23,29,30,34,44 In this context, the TRH stimulation test, by highlighting the latent capacity of the pituitary gland to respond to exogenous TRH, can improve both the assessment of the thyroid function and the management of the pregnancy impairment in women with unexplained reproductive failure. 21,34 As a remark, we reported very few patients with positive ANA titer in our study population.…”

Section: Discussionmentioning

confidence: 99%

Peripheral blood natural killer cells and mild thyroid abnormalities in women with reproductive failure

Triggianese

Perricone

Conigliaro

et al. 2015

Int J Immunopathol Pharmacol

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Abnormalities in peripheral blood natural killer (NK) cells have been reported in women with primary infertility and recurrent spontaneous abortion (RSA) and several studies have been presented to define cutoff values for abnormal peripheral blood NK cell levels in this context. Elevated levels of NK cells were observed in infertile/RSA women in the presence of thyroid autoimmunity (TAI), while no studies have been carried out, to date, on NK cells in infertile/ RSA women with non-autoimmune thyroid diseases. The contribution of this study is two-fold: (1) the evaluation of peripheral blood NK cell levels in a cohort of infertile/RSA women, in order to confirm related data from the literature; and (2) the assessment of NK cell levels in the presence of both TAI and subclinical hypothyroidism (SCH) in order to explore the possibility that the association between NK cells and thyroid function is not only restricted to TAI but also to SCH. In a retrospective study, 259 age-matched women (primary infertility [n = 49], primary RSA [n = 145], and secondary RSA [n = 65]) were evaluated for CD56+CD16+NK cells by flow cytometry. Women were stratified according to thyroid status: TAI, SCH, and without thyroid diseases (ET). Fertile women (n = 45) were used as controls. Infertile/RSA women showed higher mean NK cell levels than controls. The cutoff value determining the abnormal NK cell levels resulted ⩾15% in all the groups of women. Among the infertile/RSA women, SCH resulted the most frequently associated thyroid disorder while no difference resulted in the prevalence of TAI and ET women between patients and controls. A higher prevalence of women with NK cell levels ⩾15% was observed in infertile/RSA women with SCH when compared to TAI/ET women. According to our data, NK cell assessment could be used as a diagnostic tool in women with reproductive failure and we suggest that the possible association between NK cell levels and thyroid function can be described not only in the presence of TAI but also in the presence of non-autoimmune thyroid disorders.

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“…Although definitions of recurrent implantation failure (RIF) vary (Coughlan et al, 2014;Polanski et al, 2014), it is clear that embryo transfer commonly leads to a biochemical pregnancy [human chorionic gonadotropin (hCG) detected but no embryonic sac] or no detectable pregnancy at all. RIF appears distinct from recurrent miscarriage; that is, there is a group of women in whom pregnancy repeatedly fails very early on (Koot et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

miR-145 suppresses embryo-epithelial juxtacrine communication at implantation by modulating maternal IGF1R

Kang

Lees

Matthews

et al. 2015

Journal of Cell Science

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Successful implantation requires the synchronization of viable embryonic development with endometrial receptivity. The mechanisms allowing for the initiation of crosstalk between the embryo and the endometrium remain elusive; however, recent studies have revealed that there are alterations in endometrial microRNAs (miRs) in women suffering repeated implantation failure and that one of the altered miRs is miR-145. We assessed the role of miR-145 and its target IGF1R, in early implantation. miR-145 overexpression and IGF1R knockdown were achieved in Ishikawa endometrial cells. Quantitative PCR, western blotting and 39UTR luciferase reporter assays confirmed that IGF1R is a direct target of miR-145 in the endometrium. Attachment of mouse embryos or IGF1-coated beads to endometrial epithelial cells was used to study the effects of altered miR-145 and/or IGF1R expression on early implantation events. miR-145 overexpression or specific reduction of IGF1R impaired attachment in both cases. An IGF1R target protector prevented the miR-145-mediated reduction in IGF1R and reversed the effect of miR-145 overexpression on attachment. The data demonstrate that miR-145 influences embryo attachment by reducing the level of IGF1R in endometrium.

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Interventions to improve reproductive outcomes in women with elevated natural killer cells undergoing assisted reproduction techniques: a systematic review of literature

Abstract: None.

Cited by 63 publications

References 63 publications

Uterine NK cells: active regulators at the maternal-fetal interface

Uterine NK cells: active regulators at the maternal-fetal interface

Peripheral blood natural killer cells and mild thyroid abnormalities in women with reproductive failure

miR-145 suppresses embryo-epithelial juxtacrine communication at implantation by modulating maternal IGF1R

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