Uterine natural killer cells: insights into their cellular and molecular biology from mouse modelling

Croy, B A; He, Hong; Esadeg, Souad; Wei, Qingxia; McCartney, Daniel; Zhang, J; Borzychowski, Angela M.; Ashkar, Ali A.; Black, G.M.; Evans, SS; Chantakru, Sirirak; Heuvel, Mieke van den; Va, Paffaro; Yamada, AT

doi:10.1530/rep.0.1260149

Cited by 210 publications

(142 citation statements)

References 51 publications

(17 reference statements)

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“…Approximately 70% of the leukocytes in early decidua are uterine NK cells that are likely involved in fine tuning placental development, vascularity and subsequently fetal growth. [61][62][63] Unlike most cells of the human body, trophoblasts have limited or poor expression of the major histocompatibility antigens-human leukocyte antigen (HLA)-A and -B that are highly polymorphic. Limited or poor expression of HLA-A and -B is postulated to support the development of maternal tolerance to the fetus during pregnancy.…”

Section: Micrornas and Immune Cells At The Maternal-fetal Interfacementioning

confidence: 99%

MicroRNAs, immune cells and pregnancy

et al. 2014

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MicroRNAs (miRNAs) are a recently discovered class of non-coding RNAs that are expressed in many cell types, where they regulate the expression of complementary RNAs, thus modulating the stability and translation of mRNAs. miRNAs are predicted to regulate the expression of ,50% of all protein coding genes in mammals. Therefore, they participate in virtually all cellular processes investigated so far. Altered miRNAs expressions are associated with both physiological (pregnancy) and pathological processes (cancer). As the dynamic maternal-fetal interface plays a critical role in the maintenance of successful pregnancy, it is not surprising that the miRNAs that are unique to reproductive tissues are abundantly expressed. Research in this field has demonstrated the presence and dysregulation of a distinct set of pregnancy-associated miRNAs; however, most studies have centered on localizing various miRNAs in reproductive microdomains associated with normal or complicated pregnancies. Although several independent miRNA regulatory mechanisms associated with endometrial receptivity, immune cells, angiogenesis and placental development have been studied, miRNA-mediated regulation of pregnancy remains poorly understood. This review provides a summary of the current data on miRNA regulation as well as functional profiles of miRNAs that are found in the uterus, in immune cells associated with maternal tolerance to the fetus, and those involved in angiogenesis and placental development.

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Section: Micrornas and Immune Cells At The Maternal-fetal Interfacementioning

confidence: 99%

MicroRNAs, immune cells and pregnancy

et al. 2014

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“…Indeed, uterine NK (uNK) cells are the most likely maternal cell type to interact with trophoblast antigens in the decidua basalis because of their sheer abundance: they constitute 70% of all maternal leukocytes in the placental bed (14). uNK cells differ from peripheral NK cells in that they have a reduced lytic activity and a distinct surface receptor repertoire (14)(15)(16)(17). uNK cells support neovascularization of the decidua by producing proangiogenic and endothelial mitogenic stimulants and contribute to arterial transformation by initiating the loss of the arterial media (5,14,18,19).…”

mentioning

confidence: 99%

Paternal MHC expression on mouse trophoblast affects uterine vascularization and fetal growth

Madeja

Yadi²,

Apps³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

147

118

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The mammalian fetus represents a semiallograft within the maternal uterus yet is not rejected. This situation is particularly pronounced in species with a hemochorial type of placentation, such as humans and rodents, where maternal tissues and blood are in direct contact with fetal trophoblast and thus potentially with paternal antigens. The main polymorphic antigens responsible for graft rejection are MHC antigens. In humans the trophoblast cells invading into the decidua have a unique pattern of MHC class I expression characterized by both classical (HLA-C) and nonclassical (HLA-G and HLA-E) molecules. Whether such an unusual MHC repertoire on the surface of trophoblast is a conserved feature between species with hemochorial placentation has not been resolved. Here we demonstrate, using a range of methods, that C57BL/6 mouse trophoblast predominantly expresses only one MHC class I antigen, H2-K, at the cell surface of giant cells but lacks expression of nonclassical MHC molecules. Antigenic disparity between parental MHCs affects trophoblast-induced transformation of the uterine vasculature and, consequently, placental and fetal gowth. Maternal uterine blood vessels were more dilated, allowing for increased blood supply, in certain combinations of maternal and paternal MHC haplotypes, and these allogeneic fetuses and placentas were heavier at term compared with syngeneic controls. Thus, maternal-fetal immune interactions are instrumental to optimize reproductive success. This cross-talk has important implications for human disorders of pregnancy, such as preeclampsia and fetal growth restriction.decidual artery remodeling | uterine natural killer cells

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“…During embryogenesis, uNK cells release IFN-γ to aid in angiogenesis and vascularization of the uterus in order to support the developing fetus [31,32]. Although it remains controversial, the shift in uNK phenotype leading to tolerance may be induced by IL-15 and IL-7 [33]. Release of IL-15 from the epithelium is increased 22-fold in the subepithelial space as early 4 h post-semen exposure [34].…”

Section: Effects Of Seminal Factors In the Frtmentioning

confidence: 99%

Variability in human semen content and its potential effects in the female reproductive tract

Keogan¹,

Siegert²,

Wigdahl³

et al. 2016

J Reprod Biol Health

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Human semen is a complex medium containing high concentrations of cytokines, chemokines, and growth factors that play key roles in orchestrating immune responses during reproduction. These factors are essential to establishing conditions that facilitate fertilization and embryogenesis through modulation of local immune responses in the female reproductive tract. Typically, semen initiates a biphasic process of inflammation that is gradually resolved, leading to immune cell recruitment pivotal to clearing excess sperm and establishing tolerance of the fetal allograft. However, the identity and concentration of factors found in semenmay be altered in the male reproductive tract as a consequence of sexually transmitted infections and infertility conditions. As a result, imbalances in semen content can skew the secretory response of the cervicovaginal epithelium after deposition during heterosexual intercourse, which may distort local immune activity and lead to embryo rejection or enhanced pathogen transmission. Recognizing the array of factors contained in semen and the degree to which they vary is an essential part of understanding the impact of variations in semen content on reproductive biology and the transmission of sexually transmitted disease pathogens.

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Uterine natural killer cells: insights into their cellular and molecular biology from mouse modelling

Cited by 210 publications

References 51 publications

MicroRNAs, immune cells and pregnancy

MicroRNAs, immune cells and pregnancy

Paternal MHC expression on mouse trophoblast affects uterine vascularization and fetal growth

Variability in human semen content and its potential effects in the female reproductive tract

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