{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:17:53Z","timestamp":1791231473394,"version":"4.1.0"},"reference-count":134,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T00:00:00Z","timestamp":1656288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Natural killer (NK) cells are the predominant maternal uterine immune cell component, and they densely populate uterine mucosa to promote key changes in the post-ovulatory endometrium and in early pregnancy. It is broadly accepted that (a) immature, inactive endometrial NK (eNK) cells in the pre-ovulatory endometrium become activated and transition into decidual NK (dNK) cells in the secretory stage, peri-implantation endometrium, and continue to mature into early pregnancy; and (b) that secretory-stage and early pregnancy dNK cells promote uterine vascular growth and mediate trophoblast invasion, but do not exert their killing function. However, this may be an overly simplistic view. Evidence of specific dNK functional killer roles, as well as opposing effects of dNK cells on the uterine vasculature before and after conception, indicates the presence of a transitory secretory-stage dNK cell (s-dNK) phenotype with a unique angiodevelopmental profile during the peri-implantation period, that is that is functionally distinct from the angiomodulatory dNK cells that promote vessel destabilisation and vascular cell apoptosis to facilitate uterine vascular changes in early pregnancy. It is possible that abnormal activation and differentiation into the proposed transitory s-dNK phenotype may have implications in uterine pathologies ranging from infertility to cancer, as well as downstream effects on dNK cell differentiation in early pregnancy. Further, dysregulated transition into the angiomodulatory dNK phenotype in early pregnancy will likely have potential repercussions for adverse pregnancy outcomes, since impaired dNK function is associated with several obstetric complications. A comprehensive understanding of the uterine NK cell temporal differentiation pathway may therefore have important translational potential due to likely NK phenotypic functional implications in a range of reproductive, obstetric, and gynaecological pathologies.<\/jats:p>","DOI":"10.3389\/fendo.2022.904744","type":"journal-article","created":{"date-parts":[[2022,6,27]],"date-time":"2022-06-27T07:23:34Z","timestamp":1656314614000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Killer Timing: The Temporal Uterine Natural Killer Cell Differentiation Pathway and Implications for Female Reproductive Health"],"prefix":"10.3389","volume":"13","author":[{"given":"Rupsha","family":"Fraser","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Claudia","family":"Zenclussen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra000763","article-title":"Implantation and the Survival of Early Pregnancy","volume":"345","author":"Norwitz","year":"2001","journal-title":"New Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2010.01.003","article-title":"Human Decidual NK Cells From Gravid Uteri and NK Cells From Cycling Endometrium Are Distinct NK Cell Subsets","volume":"31","author":"Kopcow","year":"2010","journal-title":"Placenta"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-991042","article-title":"Decidualization of the Human Endometrium: Mechanisms, Functions, and Clinical Perspectives","volume":"25","author":"Gellersen","year":"2007","journal-title":"Semin Reprod Med"},{"key":"B4","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1210\/er.2014-1045","article-title":"Cyclic Decidualization of the Human Endometrium in Reproductive Health and Failure","volume":"35","author":"Gellersen","year":"2014","journal-title":"Endocr Rev"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1071\/RD09145","article-title":"Society for Reproductive Biology Founders' Lecture 2009. Preparing Fertile Soil: The Importance of Endometrial Receptivity","volume":"21","author":"Salamonsen","year":"2009","journal-title":"Reprod Fertil Dev"},{"key":"B6","doi-asserted-by":"publisher","first-page":"hoab034","DOI":"10.1093\/hropen\/hoab034","article-title":"A 3D Endometrial Organotypic Model Simulating the Acute Inflammatory Decidualisation Initiation Phase With Epithelial Induction of the Key Endometrial Receptivity Marker, Integrin \u03b1v\u03b23","volume":"2021","author":"Fraser","year":"2021","journal-title":"Hum Reprod Open"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.03065","article-title":"Transcriptional and Functional Programming of Decidual Innate Lymphoid Cells","volume":"10","author":"Vazquez","year":"2019","journal-title":"Front Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.607669","article-title":"How Do Uterine Natural Killer and Innate Lymphoid Cells Contribute to Successful Pregnancy","volume":"12","author":"Huhn","year":"2021","journal-title":"Front Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.31274","article-title":"Clearance of Senescent Decidual Cells by Uterine Natural Killer Cells in Cycling Human Endometrium","volume":"6","author":"Brighton","year":"2017","journal-title":"Elife"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/path.4057","article-title":"Impaired Decidual Natural Killer Cell Regulation of Vascular Remodelling in Early Human Pregnancies With High Uterine Artery Resistance","volume":"228","author":"Fraser","year":"2012","journal-title":"J Pathol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.jri.2015.04.003","article-title":"Decidual Natural Killer Cells Regulate Vessel Stability: Implications for Impaired Spiral Artery Remodelling","volume":"110","author":"Fraser","year":"2015","journal-title":"J Reprod Immunol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.jri.2009.08.001","article-title":"Decidual Leucocyte Populations in Early to Late Gestation Normal Human Pregnancy","volume":"82","author":"Williams","year":"2009","journal-title":"J Reprod Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.181.3.1869","article-title":"Endometrial NK Cells are Special Immature Cells That Await Pregnancy","volume":"181","author":"Manaster","year":"2008","journal-title":"J Immunol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.cell.2020.08.025","article-title":"Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19","volume":"183","author":"Kaneko","year":"2020","journal-title":"Cell"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abb7800","article-title":"Continuous Human Uterine NK Cell Differentiation in Response to Endometrial Regeneration and Pregnancy","volume":"6","author":"Strunz","year":"2021","journal-title":"Sci Immunol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1038\/s41467-019-14123-z","article-title":"Distinctive Phenotypes and Functions of Innate Lymphoid Cells in Human Decidua During Early Pregnancy","volume":"11","author":"Huhn","year":"2020","journal-title":"Nat Commun"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0698-6","article-title":"Single-Cell Reconstruction of the Early Maternal-Fetal Interface in Humans","volume":"563","author":"Vento-Tormo","year":"2018","journal-title":"Nature"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2008.00595.x","article-title":"Evolution of Non-Cytotoxic Uterine Natural Killer Cells","volume":"59","author":"Kalkunte","year":"2008","journal-title":"Am J Reprod Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-021-00739-z","article-title":"Biology and Pathology of the Uterine Microenvironment and its Natural Killer Cells","volume":"18","author":"Wang","year":"2021","journal-title":"Cell Mol Immunol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"R91","DOI":"10.1530\/REP-14-0271","article-title":"Uterine Natural Killer Cells: Supervisors of Vasculature Construction in Early Decidua Basalis","volume":"149","author":"R\u00e4tsep","year":"2015","journal-title":"Reproduction"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2006.01.009","article-title":"Human Decidual NK Cells: Unique Phenotype and Functional Properties \u2013 a Review","author":"Tabiasco","year":"2006","journal-title":"Placenta"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1038\/nm0906-991","article-title":"Killers Become Builders During Pregnancy","volume":"12","author":"Le Bouteiller","year":"2006","journal-title":"Nat Med"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030305","article-title":"Human Decidual Natural Killer Cells are a Unique NK Cell Subset With Immunomodulatory Potential","volume":"198","author":"Koopman","year":"2003","journal-title":"J Exp Med"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2009.06.123","article-title":"Effector Functions of Human Decidual NK Cells in Healthy Early Pregnancy Are Dependent on the Specific Engagement of Natural Cytotoxicity Receptors","volume":"82","author":"El Costa","year":"2009","journal-title":"J Reprod Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1210\/jc.86.4.1823","article-title":"Angiogenic Growth Factor Messenger Ribonucleic Acids in Uterine Natural Killer Cells","volume":"86","author":"Li","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deu017","article-title":"Increased Angiogenic Factor Secretion by Decidual Natural Killer Cells From Pregnancies With High Uterine Artery Resistance Alters Trophoblast Function","volume":"29","author":"Wallace","year":"2014","journal-title":"Hum Reprod"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dms015","article-title":"Extravillous Trophoblast and Decidual Natural Killer Cells: A Remodelling Partnership","volume":"18","author":"Wallace","year":"2012","journal-title":"Hum Reprod Update"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1530\/REP-10-0294","article-title":"Remodelling at the Maternal-Fetal Interface: Relevance to Human Pregnancy Disorders","volume":"140","author":"Cartwright","year":"2010","journal-title":"Reprod (Cambridge England)"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0406250","article-title":"Expression of Angiogenic Growth Factors by Uterine Natural Killer Cells During Early Pregnancy","volume":"80","author":"Lash","year":"2006","journal-title":"J Leukoc Biol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/ioaa208","article-title":"Uterine Decidual Niche Modulates the Progressive Dedifferentiation of Spiral Artery Vascular Smooth Muscle Cells During Human Pregnancy\u2020","volume":"104","author":"Ma","year":"2021","journal-title":"Biol Reprod"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/nm1452","article-title":"Decidual NK Cells Regulate Key Developmental Processes at the Human Fetal-Maternal Interface","volume":"12","author":"Hanna","year":"2006","journal-title":"Nat Med"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.humrep.a019300","article-title":"Evaluation of Oestrogen and Progesterone Receptor Expression in Uterine Mucosal Lymphocytes","volume":"11","author":"King","year":"1996","journal-title":"Hum Reprod"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod62.4.959","article-title":"Human Decidual Natural Killer Cells Express the Receptor for and Respond to the Cytokine Interleukin 15","volume":"62","author":"Verma","year":"2000","journal-title":"Biol Reprod"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222011094","article-title":"Interleukin-15 in Outcomes of Pregnancy","volume":"22","author":"Gordon","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-1309","article-title":"Proliferation of Uterine Natural Killer Cells is Induced by Human Chorionic Gonadotropin and Mediated via the Mannose Receptor","volume":"150","author":"Kane","year":"2009","journal-title":"Endocrinology"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/biolre\/ioac061","article-title":"Spatial Transcriptomic Profiles of Mouse Uterine Microenvironments at Pregnancy Day 7.5","author":"Li","year":"2022","journal-title":"Biol Reprod"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s10815-007-9152-7","article-title":"Angiogenesis in Implantation","volume":"24","author":"Torry","year":"2007","journal-title":"J Assist Reprod Genet"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.acthis.2009.04.004","article-title":"Vasculogenesis and Angiogenesis in the Endometrium During Menstrual Cycle and Implantation","volume":"112","author":"Demir","year":"2010","journal-title":"Acta Histochem"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1096\/fj.12-210310","article-title":"Uterine Natural Killer Cells Initiate Spiral Artery Remodeling in Human Pregnancy","volume":"26","author":"Robson","year":"2012","journal-title":"FASEB J"},{"key":"B40","doi-asserted-by":"publisher","first-page":"68","DOI":"10.3390\/biom12010068","article-title":"Role of Natural Killer Cells During Pregnancy and Related Complications","volume":"12","author":"Mahajan","year":"2022","journal-title":"Biomolecules"},{"key":"B41","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1093\/humupd\/6.1.28","article-title":"Uterine Leukocytes and Decidualization","volume":"6","author":"King","year":"2000","journal-title":"Hum Reprod Update"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2007.10.006","article-title":"The Unique Properties of Human NK Cells in the Uterine Mucosa","volume":"29","author":"Manaster","year":"2008","journal-title":"Placenta"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2009.00794.x","article-title":"The Unique Properties of Uterine NK Cells","volume":"63","author":"Manaster","year":"2010","journal-title":"Am J Reprod Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/nri886","article-title":"Natural Killer Cells and Pregnancy","volume":"2","author":"Moffett-King","year":"2002","journal-title":"Nat Rev Immunol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.87.5.8515","article-title":"Prolactin Induces ERK Phosphorylation in Epithelial and CD56(+) Natural Killer Cells of the Human Endometrium","volume":"87","author":"Gubbay","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.87.4.8539","article-title":"IL-15 Regulation in Human Endometrial Stromal Cells","volume":"87","author":"Dunn","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"B47","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/sj.cr.7290204","article-title":"Expression of Prolactin Receptor and Response to Prolactin Stimulation of Human NK Cell Lines","volume":"14","author":"Sun","year":"2004","journal-title":"Cell Res"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2004.02686.x","article-title":"Effects of Prolactin and Cortisol on Natural Killer (NK) Cell Surface Expression and Function of Human Natural Cytotoxicity Receptors (NKp46, NKp44 and Nkp30)","volume":"139","author":"Mavoungou","year":"2005","journal-title":"Clin Exp Immunol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1210\/er.2003-0021","article-title":"Natural Killer Cells in Pregnancy and Recurrent Pregnancy Loss: Endocrine and Immunologic Perspectives","volume":"26","author":"Dosiou","year":"2005","journal-title":"Endocr Rev"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1515\/JPM.2006.089","article-title":"Normal and Abnormal Transformation of the Spiral Arteries During Pregnancy","volume":"34","author":"Espinoza","year":"2006","journal-title":"J Perinat Med"},{"key":"B51","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1620\/tjem.193.13","article-title":"Involvement of Granule-Mediated Apoptosis in the Cyclic Changes of the Normal Human Endometrium","volume":"193","author":"Igarashi","year":"2001","journal-title":"Tohoku J Exp Med"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.106.4.1049","article-title":"The Role of the Asparagine-Linked Oligosaccharides of the Alpha Subunit in the Secretion and Assembly of Human Chorionic Gonadotrophin","volume":"106","author":"Matzuk","year":"1988","journal-title":"J Cell Biol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-540-46410-5_6","article-title":"Structure and Function of the Macrophage Mannose Receptor","volume":"33","author":"Taylor","year":"2001","journal-title":"Results Probl Cell Differ"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-4165(02)00319-7","article-title":"The Mannose Receptor Family","volume":"1572","author":"East","year":"2002","journal-title":"Biochim Biophys Acta"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/43.12.2233","article-title":"Immunoassay of Human Chorionic Gonadotropin, its Free Subunits, and Metabolites","volume":"43","author":"Cole","year":"1997","journal-title":"Clin Chem"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/15.2.469","article-title":"Predictive Value of Plasma Human Chorionic Gonadotrophin Following Assisted Conception Treatment","volume":"15","author":"Sugantha","year":"2000","journal-title":"Hum Reprod"},{"key":"B57","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1016\/j.immuni.2018.03.030","article-title":"Trained Memory of Human Uterine NK Cells Enhances Their Function in Subsequent Pregnancies","volume":"48","author":"Gamliel","year":"2018","journal-title":"Immunity"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1002\/rmb2.12088","article-title":"Decidualization of the Human Endometrium","volume":"17","author":"Okada","year":"2018","journal-title":"Reprod Med Biol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dml004","article-title":"Endometrial Receptivity Markers, the Journey to Successful Embryo Implantation","volume":"12","author":"Achache","year":"2006","journal-title":"Hum Reprod Update"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2020.05.039","article-title":"Implantation Involves an Initial Pro-Inflammatory Response","volume":"114","author":"Quenby","year":"2020","journal-title":"Fertil Steril"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0052252","article-title":"Disordered IL-33\/ST2 Activation in Decidualizing Stromal Cells Prolongs Uterine Receptivity in Women With Recurrent Pregnancy Loss","volume":"7","author":"Salker","year":"2012","journal-title":"PLoS One"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2011.07.1095","article-title":"Assessment of Endometrial Receptivity","volume":"96","author":"Lessey","year":"2011","journal-title":"Fertil Steril"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0378(01)00139-5","article-title":"Adhesion Molecules and Implantation","volume":"55","author":"Lessey","year":"2002","journal-title":"J Reprod Immunol"},{"key":"B64","doi-asserted-by":"publisher","first-page":"4991","DOI":"10.1210\/jcem.86.10.7906","article-title":"Osteopontin and its Receptor Alphavbeta(3) Integrin are Coexpressed in the Human Endometrium During the Menstrual Cycle But Regulated Differentially","volume":"86","author":"Apparao","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2012.12.011","article-title":"Physiological and Molecular Determinants of Embryo Implantation","volume":"34","author":"Zhang","year":"2013","journal-title":"Mol Aspects Med"},{"key":"B66","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.mce.2012.02.023","article-title":"The Uterus Under Hormonal Control\u2013Cycling for Life","volume":"358","author":"Brosens","year":"2012","journal-title":"Mol Cell Endocrinol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-0899","article-title":"NADPH Oxidase-Derived Reactive Oxygen Species Mediate Decidualization of Human Endometrial Stromal Cells in Response to Cyclic AMP Signaling","volume":"152","author":"Al-Sabbagh","year":"2011","journal-title":"Endocrinology"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1210\/en.2007-1633","article-title":"Prokineticin 1 Signaling and Gene Regulation in Early Human Pregnancy","volume":"149","author":"Evans","year":"2008","journal-title":"Endocrinology"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.728291","article-title":"Role of Decidual Natural Killer Cells in Human Pregnancy and Related Pregnancy Complications","volume":"12","author":"Zhang","year":"2021","journal-title":"Front Immunol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c190015","article-title":"Uterine Vascular Control Preconception and During Pregnancy","volume":"11","author":"Fournier","year":"2021","journal-title":"Compr Physiol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1002\/jemt.10279","article-title":"Endometrial Arteriogenesis: Vascular Smooth Muscle Cell Proliferation and Differentiation During the Menstrual Cycle and Changes Associated With Endometrial Bleeding Disorders","volume":"60","author":"Rogers","year":"2003","journal-title":"Microscopy Res Technique"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00317.2001","article-title":"Angiopoietin-1 and VEGF in Vascular Development and Angiogenesis in Hypoplastic Lungs","volume":"283","author":"Chinoy","year":"2002","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1177\/1947601910392987","article-title":"Tyrosine Kinase Receptor Flt\/VEGFR Family: Its Characterization Related to Angiogenesis and Cancer","volume":"1","author":"Shibuya","year":"2010","journal-title":"Genes Cancer"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1016\/S1726-4901(09)70052-8","article-title":"Roles of Estrogen and Progesterone in Endometrial Hemodynamics and Vascular Endothelial Growth Factor Production","volume":"72","author":"Wen","year":"2009","journal-title":"J Chin Med Assoc"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2141.1998.01076.x","article-title":"Role of Vascular Endothelial Growth Factor (VEGF) and Placenta-Derived Growth Factor (PlGF) in Regulating Human Haemopoietic Cell Growth","volume":"103","author":"Ratajczak","year":"1998","journal-title":"Br J Haematol"},{"key":"B76","doi-asserted-by":"publisher","first-page":"2477","DOI":"10.3390\/ijms19092477","article-title":"Inside the Endometrial Cell Signaling Subway: Mind the Gap(s)","volume":"19","author":"Makieva","year":"2018","journal-title":"Int J Mol Sci"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1016\/S1472-6483(10)60649-9","article-title":"Defective Implantation and Placentation: Laying the Blueprint for Pregnancy Complications","volume":"13","author":"Norwitz","year":"2006","journal-title":"Reprod Biomed Online"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.114.04481","article-title":"Bioinformatics Approach Reveals Evidence for Impaired Endometrial Maturation Before and During Early Pregnancy in Women Who Developed Preeclampsia","volume":"65","author":"Rabaglino","year":"2015","journal-title":"Hypertension (Dallas Tex 1979)"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2017.06.005","article-title":"Emerging Role for Dysregulated Decidualization in the Genesis of Preeclampsia","volume":"60","author":"Conrad","year":"2017","journal-title":"Placenta"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjog.2014.10.008","article-title":"Decreased Endometrial Vascularity and Receptivity in Unexplained Recurrent Miscarriage Patients During Midluteal and Early Pregnancy Phases","volume":"54","author":"Tan","year":"2015","journal-title":"Taiwanese J Obstet Gynecol"},{"key":"B81","article-title":"Recurrent Implantation Failure: The Role of the Endometrium","volume":"15","author":"Timeva","year":"2014","journal-title":"J Reprod Infertil"},{"key":"B82","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1055\/s-0031-1293203","article-title":"Clinical Assessment and Management of the Endometrium in Recurrent Early Pregnancy Loss","volume":"29","author":"Patel","year":"2011","journal-title":"Semin Reprod Med"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dml033","article-title":"The Human Endometrium as a Fertility-Determining Factor","volume":"12","author":"Strowitzki","year":"2006","journal-title":"Hum Reprod Update"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2014.02.027","article-title":"Prospective Assessment of Midsecretory Endometrial Leukemia Inhibitor Factor Expression Versus Alphanubeta3 Testing in Women With Unexplained Infertility","volume":"101","author":"Franasiak","year":"2014","journal-title":"Fertil Steril"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-991044","article-title":"Uterine Receptivity: Alterations Associated With Benign Gynecological Disease","volume":"25","author":"Donaghay","year":"2007","journal-title":"Semin Reprod Med"},{"key":"B86","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1111\/j.1749-6632.2002.tb02787.x","article-title":"Implantation Defects in Infertile Women With Endometriosis","volume":"955","author":"Lessey","year":"2002","journal-title":"Ann New York Acad Sci"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.79.2.7519194","article-title":"Aberrant Integrin Expression in the Endometrium of Women With Endometriosis","volume":"79","author":"Lessey","year":"1994","journal-title":"J Clin Endocrinol Metab"},{"key":"B88","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.rbmo.2016.05.002","article-title":"Endometrial Thickness as a Predictor of Pregnancy Outcomes in 10787 Fresh IVF-ICSI Cycles","volume":"33","author":"Yuan","year":"2016","journal-title":"Reprod BioMed Online"},{"key":"B89","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1111\/aji.12408","article-title":"Natural Killer Cells: Key Players in Endometriosis","volume":"74","author":"Thiruchelvam","year":"2015","journal-title":"Am J Reprod Immunol"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00877","article-title":"Endometrial Tumor Microenvironment Alters Human NK Cell Recruitment, and Resident NK Cell Phenotype and Function","volume":"10","author":"Degos","year":"2019","journal-title":"Front Immunol"},{"key":"B91","doi-asserted-by":"crossref","DOI":"10.4049\/jimmunol.156.10.4027","article-title":"Endometrial T, B, and NK Cells in Patients With Recurrent Spontaneous Abortion. Altered Profile and Pregnancy Outcome","volume":"156","author":"Lachapelle","year":"1996","journal-title":"J Immunol"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deh159","article-title":"No Difference in Natural Killer or Natural Killer T-Cell Population, But Aberrant T-Helper Cell Population in the Endometrium of Women With Repeated Miscarriage","volume":"19","author":"Shimada","year":"2004","journal-title":"Hum Reprod"},{"key":"B93","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1034\/j.1600-0897.2002.01048.x","article-title":"Distributions of Endometrial NK Cells, B Cells, T Cells, and Th2\/Tc2 Cells Fail to Predict Pregnancy Outcome Following Recurrent Abortion","volume":"47","author":"Michimata","year":"2002","journal-title":"Am J Reprod Immunol"},{"key":"B94","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/humupd\/dmac006","article-title":"Number and Function of Uterine Natural Killer Cells in Recurrent Miscarriage and Implantation Failure: A Systematic Review and Meta-Analysis","author":"Woon","year":"2022","journal-title":"Hum Reprod Update"},{"key":"B95","doi-asserted-by":"publisher","first-page":"194","DOI":"10.3390\/jcm10020194","article-title":"Different Background: Natural Killer Cell Profiles in Secondary Versus Primary Recurrent Pregnancy Loss","volume":"10","author":"Strobel","year":"2021","journal-title":"J Clin Med"},{"key":"B96","article-title":"The Role of the Spiral Arteries in the Pathogenesis of Preeclampsia","volume":"1","author":"Brosens","year":"1972","journal-title":"Obstet Gynecol Annu"},{"key":"B97","first-page":"Pvi","article-title":"The Role of the Spiral Arteries in the Pathogenesis of Pre-Eclampsia","volume":"101","author":"Brosens","year":"1970","journal-title":"J Pathol"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.1991.tb13450.x","article-title":"Placental Bed Spiral Arteries in the Hypertensive Disorders of Pregnancy","volume":"98","author":"Pijnenborg","year":"1991","journal-title":"Br J Obstet Gynaecol"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.1994.tb13182.x","article-title":"A Study of Placental Bed Spiral Arteries and Trophoblast Invasion in Normal and Severe Pre-Eclamptic Pregnancies","volume":"101","author":"Meekins","year":"1994","journal-title":"Br J Obstet Gynaecol"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.2002.00077.x","article-title":"Placental Massive Perivillous Fibrin Deposition Associated With Antiphospholipid Antibody Syndrome","volume":"109","author":"Sebire","year":"2002","journal-title":"BJOG an Int J Obstet Gynaecol"},{"key":"B101","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.ajog.2010.08.009","article-title":"The \u201cGreat Obstetrical Syndromes\u201d Are Associated With Disorders of Deep Placentation","volume":"204","author":"Brosens","year":"2011","journal-title":"Am J Obstet Gynecol"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4004(98)90055-8","article-title":"Decidual Spiral Artery Remodelling Begins Before Cellular Interaction With Cytotrophoblasts","volume":"19","author":"Craven","year":"1998","journal-title":"Placenta"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.080995","article-title":"Evidence for Immune Cell Involvement in Decidual Spiral Arteriole Remodeling in Early Human Pregnancy","volume":"174","author":"Smith","year":"2009","journal-title":"Am J Pathol"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.091105","article-title":"Vascular-Leukocyte Interactions: Mechanisms of Human Decidual Spiral Artery Remodeling In Vitro","volume":"177","author":"Hazan","year":"2010","journal-title":"Am J Pathol"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2005.12.006","article-title":"The Uterine Spiral Arteries in Human Pregnancy: Facts and Controversies","volume":"27","author":"Pijnenborg","year":"2006","journal-title":"Placenta"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2016.08.019","article-title":"Variation of Maternal KIR and Fetal HLA-C Genes in Reproductive Failure: Too Early for Clinical Intervention","volume":"33","author":"Moffett","year":"2016","journal-title":"Reprod Biomed Online"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2011.04.006","article-title":"Uterine and Circulating Natural Killer Cells and Their Roles in Women With Recurrent Pregnancy Loss, Implantation Failure and Preeclampsia","volume":"90","author":"Fukui","year":"2011","journal-title":"J Reprod Immunol"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1172\/JCI43998","article-title":"Maternal Activating KIRs Protect Against Human Reproductive Failure Mediated by Fetal HLA-C2","volume":"120","author":"Hiby","year":"2010","journal-title":"J Clin Invest"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041214","article-title":"Combinations of Maternal KIR and Fetal HLA-C Genes Influence the Risk of Preeclampsia and Reproductive Success","volume":"200","author":"Hiby","year":"2004","journal-title":"J Exp Med"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1400577","article-title":"Maternal KIR in Combination With Paternal HLA-C2 Regulate Human Birth Weight","volume":"192","author":"Hiby","year":"2014","journal-title":"J Immunol"},{"key":"B111","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/j.placenta.2010.04.012","article-title":"Role of Interleukin 8 in Uterine Natural Killer Cell Regulation of Extravillous Trophoblast Cell Invasion","volume":"31","author":"De Oliveira","year":"2010","journal-title":"Placenta"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2009.01.013","article-title":"Interleukin-6 Stimulates Cell Migration, Invasion and Integrin Expression in HTR-8\/SVneo Cell Line","volume":"30","author":"Jovanovi\u0107","year":"2009","journal-title":"Placenta"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1387\/ijdb.082769mk","article-title":"Critical Growth Factors and Signalling Pathways Controlling Human Trophoblast Invasion","volume":"54","author":"Kn\u00f6fler","year":"2010","journal-title":"Int J Dev Biol"},{"key":"B114","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1095\/biolreprod.105.045518","article-title":"The Chemokines, CX3CL1, CCL14, and CCL4, Promote Human Trophoblast Migration at the Feto-Maternal Interface","volume":"74","author":"Hannan","year":"2006","journal-title":"Biol Reprod"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.08.023","article-title":"Decidual Natural Killer Cell Interactions With Trophoblasts Are Impaired in Pregnancies at Increased Risk of Preeclampsia","volume":"183","author":"Wallace","year":"2013","journal-title":"Am J Pathol"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1111\/aji.13054","article-title":"Decidual Leucocytes Infiltrating Human Spiral Arterioles are Rich Source of Matrix Metalloproteinases and Degrade Extracellular Matrix In Vitro and in Situ","volume":"81","author":"Choudhury","year":"2019","journal-title":"Am J Reprod Immunol"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2010.11.018","article-title":"IFPA Gabor Than Award Lecture: Transformation of the Spiral Arteries in Human Pregnancy: Key Events in the Remodelling Timeline","author":"Harris","year":"2011","journal-title":"Placenta"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2007.11.008","article-title":"Regulation of Trophoblast Invasion - A Workshop Report","volume":"29","author":"Kn\u00f6fler","year":"2008","journal-title":"Placenta"},{"key":"B119","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1177\/1933719107309588","article-title":"Vascular Remodeling and Extracellular Matrix Breakdown in the Uterine Spiral Arteries During Pregnancy","volume":"14","author":"Harris","year":"2007","journal-title":"Reprod Sci (Thousand Oaks Calif)"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1530\/REP-09-0341","article-title":"Interleukin-8 (CXCL8) Stimulates Trophoblast Cell Migration and Invasion by Increasing Levels of Matrix Metalloproteinase (MMP)2 and MMP9 and Integrins Alpha5 and Beta1","volume":"139","author":"Jovanovi\u0107","year":"2010","journal-title":"Reprod (Cambridge England)"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2009.12.011","article-title":"Decidual NK Cell-Derived Conditioned Medium Enhances Capillary Tube and Network Organization in an Extravillous Cytotrophoblast Cell Line","volume":"31","author":"Hu","year":"2010","journal-title":"Placenta"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gal100","article-title":"Soluble HLA-G Promotes Th1-Type Cytokine Production by Cytokine-Activated Uterine and Peripheral Natural Killer Cells","volume":"13","author":"van der Meer","year":"2007","journal-title":"Mol Hum Reproduct"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gah032","article-title":"Membrane-Bound HLA-G Activates Proliferation and Interferon-Gamma Production by Uterine Natural Killer Cells","volume":"10","author":"van der Meer","year":"2004","journal-title":"Mol Hum Reproduct"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0901173106","article-title":"HLA-G Homodimer-Induced Cytokine Secretion Through HLA-G Receptors on Human Decidual Macrophages and Natural Killer Cells","volume":"106","author":"Li","year":"2009","journal-title":"Proc Natl Acad Sci USA"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/5.11.1055","article-title":"Effects of Interleukin-6 (IL-6) on Cytotrophoblastic Cells","volume":"5","author":"Meisser","year":"1999","journal-title":"Mol Hum Reproduct"},{"key":"B126","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1093\/molehr\/gas010","article-title":"Effects of Interleukin-6 on Extravillous Trophoblast Invasion in Early Human Pregnancy","volume":"18","author":"Champion","year":"2012","journal-title":"Mol Hum Reproduct"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.3.913","article-title":"Protection From Lysis by Natural Killer Cells of Group 1 and 2 Specificity Is Mediated by Residue 80 in Human Histocompatibility Leukocyte Antigen C Alleles and Also Occurs With Empty Major Histocompatibility Complex Molecules","volume":"184","author":"Mandelboim","year":"1996","journal-title":"J Exp Med"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601279","article-title":"Activating KIR2DS4 Is Expressed by Uterine NK Cells and Contributes to Successful Pregnancy","volume":"197","author":"Kennedy","year":"2016","journal-title":"J Immunol"},{"key":"B129","doi-asserted-by":"publisher","DOI":"10.1172\/JCI68991","article-title":"Maternal Uterine NK Cell-Activating Receptor KIR2DS1 Enhances Placentation","volume":"123","author":"Xiong","year":"2013","journal-title":"J Clin Invest"},{"key":"B130","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1189\/jlb.2A0614-282R","article-title":"Decidual Natural Killer Cell Receptor Expression is Altered in Pregnancies With Impaired Vascular Remodeling and a Higher Risk of Pre-Eclampsia","volume":"97","author":"Wallace","year":"2015","journal-title":"J Leukoc Biol"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2010.12.005","article-title":"The Human Decidual NK-Cell Response to Virus Infection: What can We Learn From Circulating NK Lymphocytes","volume":"88","author":"Le Bouteiller","year":"2011","journal-title":"J Reprod Immunol"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003257","article-title":"Human Cytomegalovirus Infection Elicits New Decidual Natural Killer Cell Effector Functions","volume":"9","author":"Siewiera","year":"2013","journal-title":"PLoS Pathog"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2115410118","article-title":"Decidual NK Cells Kill Zika Virus-Infected Trophoblasts","volume":"118","author":"Sen Santara","year":"2021","journal-title":"Proc Natl Acad Sci USA"},{"key":"B134","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1016\/j.cell.2020.07.019","article-title":"Decidual NK Cells Transfer Granulysin to Selectively Kill Bacteria in Trophoblasts","volume":"182","author":"Crespo","year":"2020","journal-title":"Cell"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.904744\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T17:29:21Z","timestamp":1675963761000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.904744\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,27]]},"references-count":134,"alternative-id":["10.3389\/fendo.2022.904744"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.904744","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,27]]},"article-number":"904744"}}