Uterine natural killer cells and angiogenesis in recurrent reproductive failure

Quenby, Siobhán; Nik, Helena; Innes, Barbara A.; Lash, Gendie E.; Turner, Mark A.; Drury, J; Bulmer, Judith N.

doi:10.1093/humrep/den348

Cited by 215 publications

(178 citation statements)

References 35 publications

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“…Complications of pregnancy: threatened miscarriage at different gestational age, infertility, and ART failures in particular, are also associated with the increase in the content of natural killer cells and the increase in the number of T-cytotoxic lymphocytes and B cells [15,16].…”

Section: Discussionmentioning

confidence: 99%

Risk factors vary early preterm birth and perinatal complications after assisted reproductive technology

Chistyakova

Gazieva

Ремизова

et al. 2016

Gynecological Endocrinology

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We conducted a study of markers of endothelial dysfunction and angiogenesis regulation, as well as the identification of the main lymphocyte populations, activated CD3 + CD95+ -cells and cytokine-producing CD4 + IFN-g + -, CD4 + IL-4 + -lymphocytes in the 1st trimester of gestation in women with ART-induced pregnancy and spontaneous pregnancy. We used the same indicators to assess the immune status of ELBW infants at birth and at the post-conceptual age of 38-40 weeks. It was determined that the risk factors of very early preterm delivery are: threatened miscarriage, chronic placental insufficiency, endothelial dysfunction, increased spontaneous production of intracellular cytokines. Adverse perinatal outcomes in ELBW infants from ART-induced pregnancy are associated with lower anthropometric measures, low Apgar scores high level of inflammatory infections (pneumonia), grade II intraventricular hemorrhage, movement disorders in the form of lower paraparesis. Immune status of those infants is characterized by the increase in the number of CD8 + -and CD3 À CD16 + CD56 + -lymphocytes, the expression level of Fas-receptor by T-cells, and the increased production of intracellular and serum IFNg against the decrease in the number of CD4 + -cells, which indicates enhancing of cytotoxic effector potential and proinflammatory orientation of cell responses.

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Section: Discussionmentioning

confidence: 99%

Risk factors vary early preterm birth and perinatal complications after assisted reproductive technology

Chistyakova

Gazieva

Ремизова

et al. 2016

Gynecological Endocrinology

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“…It is postulated that this exposes implanting blastocysts to excessive oxidative stress, leading to embryonic loss. 67 Opposite clinical thinking is also reported. For example, some infertility patients planning to undergo embryo transfer, use a clinical protocol developed to stimulate uNK cells.…”

Section: 56mentioning

confidence: 96%

Natural killer cell-triggered vascular transformation: maternal care before birth?

et al. 2010

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Natural killer (NK) cells are found in lymphoid and non-lymphoid organs. In addition to important roles in immune surveillance, some NK cells contribute to angiogenesis and circulatory regulation. The uterus of early pregnancy is a non-lymphoid organ enriched in NK cells that are specifically recruited to placental attachment sites. In species with invasive hemochorial placentation, these uterine natural killer (uNK) cells, via secretion of cytokines, chemokines, mucins, enzymes and angiogenic growth factors, contribute to the physiological change of mesometrial endometrium into the unique stromal environment called decidua basalis. In humans, uNK cells have the phenotype CD56 bright CD16 dim and they appear in great abundance in the late secretory phase of the menstrual cycle and early pregnancy. Gene expression studies indicate that CD56 bright CD16 dim uterine and circulating cells are functionally distinct. In humans but not mice or other species with post-implantation decidualization, uNK cells may contribute to blastocyst implantation and are of interest as therapeutic targets in female infertility. Histological and genetic studies in mice first identified triggering of the process of gestation spiral arterial modification as a major uNK cell function, achieved via interferon (IFN)-c secretion. During spiral arterial modification, branches from the uterine artery that traverse the endometrium/decidua transiently lose their muscular coat and ability to vasoconstrict. The expression of vascular markers changes from arterial to venous as these vessels dilate and become low-resistance, high-volume channels. Full understanding of the vascular interactions of human uNK cells is difficult to obtain because endometrial time-course studies are not possible in pregnant women. Here we briefly review key information concerning uNK cell functions from studies in rodents, summarize highlights concerning human uNK cells and describe our preliminary studies on development of a humanized, pregnant mouse model for in vivo investigations of human uNK cell functions.

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“…The interaction between the endometrium and the trophectodermal cells of the blastocyst is one of the crucial moments for the beginning and maintenance of successful pregnancy (2). In cases of deregulation, different pathologies in human reproduction could be presented such as: recurrent implantation failures, recurrent miscarriages (RM) or endometriosis (3,4).…”

Section: Introductionmentioning

confidence: 99%

Association of angiogenic cytokines (VEGF-A and VEGF-C) and clinical characteristic in women with unexplained recurrent miscarriage

Bagheri¹,

Kumar²,

Kamath³

et al. 2017

BLL

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INTRODUCTION: Recurrent miscarriage (RM) defi ned as 2 or more spontaneous miscarriage before 20 weeks of gestation, affects at least 1 % of couples trying to conceive. In over 50 % of cases, the cause of the loss of pregnancy remains unexplained. Reduced expression of Angiogenic factors such as: vascular endothelial growth factor (VEGF-A) and VEGF-C has been linked with spontaneous miscarriage, likely due to defective foetal and placental angiogenesis. AIMS AND OBJECTIVES: To investigate the relationships between serum level of VEGF-A and VEGF-C with clinical characteristic in women with URM and compare to pregnant and healthy women. MATERIALS AND METHODS: A case-control study, which was conducted between 90 non-pregnant women with history of RM, age-matched with 70 non-pregnant women without history of recurrent abortion with at least one child (controls) and 70 pregnant women without history of recurrent abortion with at least one child (controls). Those with unexplained RM were eligible. Demographic and Anthropometric data were retrieved by pre-test questionnaire and serum level of VEGF-A and VEGF-C measured by ELISA kit. RESULTS: This study showeds that maternal levels of VEGF-A and VEGF-C were distinctly lower in RSA (189.87±88.1 vs 238.8±99.6) compared to healthy (239.1±99.7 vs 275.5±133.08) and pregnant (301.5±76.4 vs 402.5±128.6) women as control groups. Univariate analysis demonstrated that clinical characteristic factors were signifi cantly associated with concentration of VEGF-A and VEGF-C in cases and controls. CONCLUSIONS: Our fi ndings suggest that these molecules could be used as potential predictive markers of miscarriage in these women presenting with URM (Tab. 4, Fig. 5, Ref. 40). Text in PDF www.elis.sk.

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Uterine natural killer cells and angiogenesis in recurrent reproductive failure

Cited by 215 publications

References 35 publications

Risk factors vary early preterm birth and perinatal complications after assisted reproductive technology

Risk factors vary early preterm birth and perinatal complications after assisted reproductive technology

Natural killer cell-triggered vascular transformation: maternal care before birth?

Association of angiogenic cytokines (VEGF-A and VEGF-C) and clinical characteristic in women with unexplained recurrent miscarriage

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