Abstract
During early pregnancy, fetal-derived extravillous trophoblast cells (EVT) from the placenta invade the maternal decidua and inner third of the uterus where they establish fetal tolerance and remodel the uterine spiral arteries, which ensures establishment of a successful pregnancy. Aberrant EVT invasion and spiral artery remodeling is associated with a number of pregnancy complications including miscarriage, preeclampsia, fetal growth restriction, and placenta accrete. During invasion of the maternal tissues, the EVT interact with a number of different cell types including the decidual leukocytes. EVT express HLA-C, HLA-G, HLA-E, and HLA-F and interact with uterine natural killer (uNK) cells through a series of different receptors. Epidemiological evidence suggests that different combinations of HLA-C and killer cell Ig-like receptor (KIR) haplotypes impact pregnancy success. Therefore, there is much interest in the functional consequence of interactions between EVT and uNK cells, and several different methodologies have been used to isolate these different cell types and their co-culture.
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References
Knofler M et al (2019) Human placenta and trophoblast development: key molecular mechanisms and model systems. Cell Mol Life Sci 76(18):3479–3496
O’Tierney-Ginn PF, Lash GE (2014) Beyond pregnancy: modulation of trophoblast invasion and its consequences for fetal growth and long-term children’s health. J Reprod Immunol 104-105:37–42
Khong TY et al (1986) Inadequate maternal vascular response to placentation in pregnancies complicated by pre-eclampsia and by small-for-gestational age infants. Br J Obstet Gynaecol 93(10):1049–1059
Pijnenborg R et al (1991) Placental bed spiral arteries in the hypertensive disorders of pregnancy. Br J Obstet Gynaecol 98(7):648–655
Ball E et al (2006) Late sporadic miscarriage is associated with abnormalities in spiral artery transformation and trophoblast invasion. J Pathol 208(4):535–542
Raulet DH, Vance RE (2006) Self-tolerance of natural killer cells. Nat Rev Immunol 6(7):520–531
Lanier LL (2005) NK cell recognition. Annu Rev Immunol 23:225–274
Hiby SE et al (2004) Combinations of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success. J Exp Med 200(8):957–965
Hiby SE et al (2008) Association of maternal killer-cell immunoglobulin-like receptors and parental HLA-C genotypes with recurrent miscarriage. Hum Reprod 23(4):972–976
Hiby SE et al (2010) Maternal activating KIRs protect against human reproductive failure mediated by fetal HLA-C2. J Clin Invest 120(11):4102–4110
Hiby SE et al (2014) Maternal KIR in combination with paternal HLA-C2 regulate human birth weight. J Immunol 192(11):5069–5073
Sharkey AM et al (2015) Tissue-specific education of decidual NK cells. J Immunol 195(7):3026–3032
Tilburgs T et al (2015) Human HLA-G+ extravillous trophoblasts: immune-activating cells that interact with decidual leukocytes. Proc Natl Acad Sci U S A 112(23):7219–7224
Lash GE et al (2011) Interaction between uterine natural killer cells and extravillous trophoblast cells: effect on cytokine and angiogenic growth factor production. Hum Reprod 26(9):2289–2295
Cervar-Zivkovic M, Stern C (2011) Trophoblast isolation and culture. In: The Placenta. Wiley, pp 153–162
Lash GE et al (2009) IFPA meeting 2008 workshops report. Placenta 30(Suppl A):S4–S14
Bulmer JN, Lash GE (2005) Human uterine natural killer cells: a reappraisal. Mol Immunol 42(4):511–521
Vento-Tormo R et al (2018) Single-cell reconstruction of the early maternal-fetal interface in humans. Nature 563(7731):347–353
Olga Genbacev SAS, Miller RK (1992) Villous culture of first trimester human placenta- model to study extravillous trophoblast (EVT) differentiation. Placenta 13:22
Vicovac L, Jones CJ, Aplin JD (1995) Trophoblast differentiation during formation of anchoring villi in a model of the early human placenta in vitro. Placenta 16(1):41–56
Caniggia I et al (1997) Endoglin regulates trophoblast differentiation along the invasive pathway in human placental villous explants. Endocrinology 138(11):4977–4988
James JL, Stone PR, Chamley LW (2005) Cytotrophoblast differentiation in the first trimester of pregnancy: evidence for separate progenitors of extravillous trophoblasts and syncytiotrophoblast. Reproduction 130(1):95–103
Tarrade A et al (2001) Characterization of human villous and extravillous trophoblasts isolated from first trimester placenta. Lab Investig 81(9):1199–1211
Lash GE et al (2010) Secretion of angiogenic growth factors by villous cytotrophoblast and extravillous trophoblast in early human pregnancy. Placenta 31(6):545–548
Biadasiewicz K et al (2014) Extravillous trophoblast-associated ADAM12 exerts pro-invasive properties, including induction of integrin beta 1-mediated cellular spreading. Biol Reprod 90(5):101
Borbely AU et al (2014) The term basal plate of the human placenta as a source of functional extravillous trophoblast cells. Reprod Biol Endocrinol 12:7
Male V et al (2010) Natural killer cells in human pregnancy. Methods Mol Biol 612:447–463
Male V, Gardner L, Moffett A (2012) Isolation of cells from the feto-maternal interface. Curr Protoc Immunol Chapter 7:Unit 7 40 1–11. https://doi.org/10.1002/0471142735.im0740s97
Fonseca BM et al (2020) Decidual NK cell-derived conditioned medium from miscarriages affects endometrial stromal cell decidualisation: endocannabinoid anandamide and tumour necrosis factor-alpha crosstalk. Hum Reprod 35(2):265–274
Trundley A et al (2006) Methods for isolation of cells from the human fetal-maternal interface. Methods Mol Med 122:109–122
Blaschitz A et al (2000) Antibody reaction patterns in first trimester placenta: implications for trophoblast isolation and purity screening. Placenta 21(7):733–741
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Gan, X., Ning, F., Lash, G.E. (2024). Methods for Co-culture of Primary Human Extravillous Trophoblast Cells and Uterine Natural Killer Cells. In: Raha, S. (eds) Trophoblasts. Methods in Molecular Biology, vol 2728. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3495-0_16
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DOI: https://doi.org/10.1007/978-1-0716-3495-0_16
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