Natural killer and miscarriage

OBJECTIVE: To study the distribution and gene expression of endometrial immune cell populations, especially natural killer (NK) subsets, between assisted reproductive technology patients and healthy donors and explore a possible relationship of these results with patients' killer cell immunoglobulin-like receptor (KIR) genotypes and KIR-human antigen leukocyte-C (HLA-C) binding. DESIGN: Prospective observational cohort study. SETTING: Clinic and university laboratories...

This study aimed to develop reference intervals (RIs) of endometrial immune cells in control infertile women during the mid-luteal phase, and compare with the proportion of endometrial immune cells in recurrent reproductive failure (RRF) patients. Endometrial tissue sections were obtained from 113 fertile women and 79 patients with RRF, including 40 patients who had suffered recurrent miscarriage (RM) and 39 patients with repeated implantation failure (RIF) during the mid-luteal phase of the menstrual cycle...

PURPOSE: The aim of this study was to explore the predictive role of microRNAs (miRNAs) from maternal serum exosomes in early recurrent pregnancy loss (RPL) and the related mechanism in early pregnancy. METHODS: Maternal serum was collected from pregnant women with RPL history or women with ongoing pregnancy (OP); serum exosomes were extracted and identified. Differentially expressed (DE) miRNAs in exosomes were screened by RNA sequencing and further validated by qRT-PCR...

Infertility affects approximately 48 million couples globally. Despite the enormous progress of the methods of reproductive medicine that has been made since the first test-tube baby was born in 1978, the implantation rate of day-3 embryos is only around 15-20 % and 30 % of day-5 embryos. Numerous strategies aim to improve implantation rates and prevent repeated implantation failure, however there is no specific general recommendation leading to satisfying results. One of the many risk factors relevant in this regard is the uterine immunological make-up, mainly the uterine Natural Killer (uNK) cells...

The cause for at least 50% of recurrent miscarriages (RM) is unclear, defined as unexplained recurrent miscarriages (uRM). B7-H1 (PD-L1), a molecule of the B7 family, promotes tumor development by modulating immune evasion, and recent researchers have also attached importance to the role of B7-H3, another molecule of B7 family, in tumor. Based on the similarity between growth and immune response in tumors and pregnancy, we first explored the role of B7-H3 in uRM. We found reduced levels of B7-H3 in villus tissue of uRM patients, and it was mainly expressed on the cell membrane of extravillous trophoblasts (EVT)...

PURPOSE OF THE REVIEW: Pregnancy brings about an intricate assortment of dynamic changes, which causes proper connection of genetically discordant maternal and foetal tissues. Uterine NK cells are immune cells populating the endometrium and play a major role in implantation and also regulate placentation. This review mainly aims explore the role of uterine NK cells in implantation and how it is affecting in adverse pregnancy outcomes. RECENT FINDINGS: Though the functions of uterine NK (uNK) cells are not clearly understood, NK cell activity plays a vital role during immunomodulation which is the main step in implantation and sustaining the early pregnancy...

AIM: To investigate the therapeutic effect of co-administration of tacrolimus (TAC) and low-molecular-weight heparin (LMWH) or LMWH only on pregnancy outcomes in the female with a history of implantation failure and elevated peripheral blood natural killer (pNK) cell proportion in frozen-thawed embryo transfer cycles. METHODS: To evaluate the pregnancy parameters for 249 patients with ≥2 implantation failures and pNK cell proportion ≥12% by analyzing a retrospective observational cohort study...

Recurrent pregnancy loss (RPL) affects 1-2% of couples of reproductive age. Immunological analysis of the immune status in RPL patients might contribute to the diagnosis and treatment of RPL. However, the exact immune cell composition in RPL patients is still unclear. Here, we used flow cytometry to investigate the immune cell profiles of peripheral blood and decidual tissue of women who experienced RPL. We divided peripheral immune cells into 14 major subgroups, and the percentages of T, natural killer T (NKT)-like and B cells in peripheral blood were increased in RPL patients...

Recurrent pregnancy loss (RPL) affects 1.9 % of couples. Despite the severe physical, psychological, and economic impact of RPL, miscarriage care provision remains highly heterogeneous. Due to the absence of strong scientific evidence, national and international guidelines on the diagnosis and treatment of this condition remain unclear and often contradictory. In the absence of identifiable RPL-associated risk factors, when the condition is termed "idiopathic", immunological tests and immunomodulatory treatments are sometimes suggested even though the contribution of aberrant immune activity to this condition remains undetermined...

Uterine natural killer cells (uNK) play an important role in promoting successful pregnancy by regulating trophoblast invasion and spiral artery remodelling in the first trimester. Recently, single-cell RNA sequencing (scRNAseq) on first-trimester decidua showed that uNK can be divided into three subsets, which may have different roles in pregnancy. Here we present an integration of previously published scRNAseq datasets, together with novel flow cytometry data to interrogate the frequency, phenotype, and function of uNK1-3 in seven stages of the reproductive cycle (menstrual, proliferative, secretory phases of the menstrual cycle; first, second, and third trimester; and postpartum)...

Upon embryo implantation, the uterine mucosa - the endometrium - transforms into a robust decidual matrix that accommodates the fetal placenta throughout pregnancy. This transition is driven by the differentiation of endometrial fibroblasts into specialised decidual cells. A synchronised influx of circulating natural killer (NK) cells and bone marrow-derived mesenchymal stem/progenitor cells (BM-MSC) is pivotal for decidual homeostasis and expansion in early pregnancy. We hypothesise that pathological signals interfering with the recruitment or activity of extrauterine cells at the maternal-fetal interface link miscarriage to subsequent adverse pregnancy outcomes, including further pregnancy losses and preterm labour...

BACKGROUND: The use of peri-implantation glucocorticoids has been advocated to improve embryo implantation during assistive reproductive technology (ART) cycles such as in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI). It has been proposed that glucocorticoids may improve the intrauterine environment by acting as immunomodulators to reduce the uterine natural killer (NK) cell count and activity, normalising the cytokine expression profile in the endometrium and by suppression of endometrial inflammation...

GATA2 deficiency is a disease with a broad spectrum of clinical presentation, ranging from lymphedema, deafness, pulmonary dysfunction to miscarriage and urogenital anomalies, but it is mainly recognized as an immune system and bone marrow disorder. It is caused by various heterozygous mutations in the GATA2 gene, encoding for a zinc finger transcription factor with a key role for the development and maintenance of a pool of hematopoietic stem cells; notably, most of these mutations arise de novo . Patients carrying a mutated allele usually develop a loss of some cell populations, such as B-cell, dendritic cell, natural killer cell, and monocytes, and are predisposed to disseminated human papilloma virus and mycobacterial infections...

OBJECTIVE: While immune cells were originally thought to only play a role in maternal tolerance of the semiallogenic fetus, an active role in pregnancy establishment is becoming increasingly apparent. Uterine natural killer (uNK) cells are of specific interest because of their cyclic increase in number during the window of implantation. As a distinct entity from their peripheral blood counterparts, understanding the biology and function of uNK cells will provide the framework for understanding their role in early pregnancy establishment and adverse pregnancy outcomes...

Placental syndromes include pregnancy loss, fetal growth restriction, preeclampsia, preterm delivery, premature rupture of membranes, placental abruption and intrauterine fetal demise. This paper discusses the common etiopathogenesis of those syndromes and the role of angiogenic biomarkers in their development. Pregnancy implantation, placental development and maternal adaptation are complex processes in which fetal and maternal cells interact. The syncytiotrophoblast, trophoblast, uterine natural killer cells and regulatory T cells interfere and interact in all the above-mentioned processes...

Uterine natural killer (uNK) cells are an immune subset located in the uterus. uNK cells have distinct tissue-specific characteristics compared to their counterparts in peripheral blood and lymphoid organs. Based on their location and the pregnancy status of the host, uNK cells are classified as endometrial NK (eNK) cells or decidua NK (dNK) cells. uNK cells are important in protecting the host from pathogen invasion and contribute to a series of physiological processes that affect successful pregnancy, including uterine spiral artery remodeling, fetal development, and immunity tolerance...

INTRODUCTION: Women with repeated implantation failure (RIF) and unexplained recurrent miscarriage (RM) are proposed to be at opposite ends of the implantation spectrum, with RM representing an overly receptive endometrium (implantation of genetically aberrant or poor-quality embryos) versus RIF representing an overly selective endometrium (no implantation even with good quality embryos). In both cases, often no explanation for reproductive failure can be found and although promising add-on treatments have been introduced, therapeutic options are frequently limited to supportive care...

Immune cells are essential for endometrial receptivity to embryo implantation and early placental development. They exert tissue-remodeling and immune regulatory roles-acting to promote epithelial attachment competence, regulate the differentiation of decidual cells, remodel the uterine vasculature, control and resolve inflammatory activation, and suppress destructive immunity to paternally inherited alloantigens. From a biological perspective, the endometrial immune response exerts a form of "quality control"-it promotes implantation success when conditions are favorable but constrains receptivity when physiological circumstances are not ideal...

OBJECTIVE: To compare the immunologic profiles of peripheral and menstrual blood (MB) of women who experience recurrent pregnancy loss and women without pregnancy complications. DESIGN: Explorative case-control study. Cross-sectional assessment of flow cytometry-derived immunologic profiles. SETTING: Academic medical center. PATIENT(S): Women who experienced more than 2 consecutive miscarriages. INTERVENTION(S): None...

BACKGROUND: During early pregnancy, a large number of CD56bright natural killer cells (NKs) are accumulated in the decidua; unlike peripheral and cord blood NK cells (pNK and cNK), these decidual NK cells (dNK) display a great capacity to secrete a series of angiogenic/vascular factors, which are essential for placental development. However, the mechanism underlying the formation of dNK cells with an angiogenic phenotype remains unclear. METHODS: First, we compared the difference between dNK and cNK/pNK cells in terms of the expression of CD56 and VEGF, and the regulation of the tube formation...