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3 - In vitro models for studying pre-eclampsia

from Part I - Basic science

Published online by Cambridge University Press:  03 September 2009

By
John D. Aplin  and
Ian P. Crocker
Edited by
Fiona Lyall  and
Michael Belfort
Fiona Lyall
Affiliation:
University of Glasgow
Michael Belfort
Affiliation:
University of Utah
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Summary

Introduction

Profound morphological changes occur during the comparatively short life span of the placenta (Benirschke and Kaufmann, 2000; Fox, 1997). Most of these can be related directly to functional requirements; establishing support for fetal development and growth, maintaining an immunological barrier and adjusting maternal physiology to meet the demands of pregnancy. Histology and ultrastructure present snapshots of cell and tissue behavior, but not an account of cellular interactions or pathological mechanisms. Appropriate and robust in vitro models are therefore essential in bridging the gap between structure and function, as they can accommodate mechanistic questions and offer scope for the design and testing of possible therapeutic interventions. Models should mimic cell responses in vivo and go at least part way to reflecting physiological events within the placenta. Experimental levels range from tissue perfusion to explant and cell culture. Recently, genomic, transcriptomic, proteomic and computational biology approaches have become available to complement and extend in vitro methodologies. To appreciate how these models have been applied to studying pre-eclampsia, and the scope of the in vitro methods currently available, it is convenient to divide the placenta into structurally and functionally distinct compartments, i.e. the chorionic villus and the placental bed. In turn, we have subdivided these into individual cellular components, namely those of the trophoblast, vasculature and stroma.

Villus components

Cytotrophoblast and syncytiotrophoblast in primary culture

Cytotrophoblast cells of the human placenta are the precursors of all other trophoblast phenotypes. As such, a variety of methods have been employed for their purification.

Type
Chapter
Information
Pre-eclampsia
Etiology and Clinical Practice
 , pp. 37 - 49
Publisher: Cambridge University Press
Print publication year: 2007

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References

Aplin, J. D. (1991). Implantation, trophoblast differentiation and haemochorial placentation: mechanistic evidence in vivo and in vitro. J. Cell Sci., 99(4), 681–92.Google ScholarPubMed
Aplin, J. D., Haigh, T., Jones, C. J., Church, H. J. and Vicovac, L. (1999). Development of cytotrophoblast columns from explanted first-trimester human placental villi: role of fibronectin and integrin alpha5beta1. Biol. Reprod., 60, 828–38.CrossRefGoogle ScholarPubMed
Aplin, J. D., Haigh, T., Vicovac, L., Church, H. J. and Jones, C. J. (1998). Anchorage in the developing placenta: an overlooked determinant of pregnancy outcome?Hum. Fertil. (Camb.), 1, 75–9.CrossRefGoogle ScholarPubMed
Aronow, B. J., Richardson, B. D. and Handwerger, S. (2001). Microarray analysis of trophoblast differentiation: gene expression reprogramming in key gene function categories. Physiol. Genomics, 6, 105–16.CrossRefGoogle ScholarPubMed
Ashton, S. V., Whitley, G. S., Dash, P. R., et al. (2005). Uterine spiral artery remodeling involves endothelial apoptosis induced by extravillous trophoblasts through Fas/FasL interactions. Arterioscler. Thromb. Vasc. Biol., 25(1), 102–8.Google ScholarPubMed
Benirschke, K. and Kaufmann, P. (2000). Pathology of the Human Placenta. New York: Springer Verlag.CrossRefGoogle Scholar
Blaschitz, A., Weiss, U., Dohr, G. and Desoye, G. (2000). Antibody reaction patterns in first trimester placenta: implications for trophoblast isolation and purity screening. Placenta, 21, 733–41.CrossRefGoogle ScholarPubMed
Bloxam, D. L., Bax, B. E. and Bax, C. M. (1997). Culture of syncytiotrophoblast for the study of human placental transfer. Part II: Production, culture and use of syncytiotrophoblast. Placenta, 18, 99–108.CrossRefGoogle Scholar
Campbell, S., Rowe, J., Jackson, C. J. and Gallery, E. D. (2003). In vitro migration of cytotrophoblasts through a decidual endothelial cell monolayer: the role of matrix metalloproteinases. Placenta, 24, 306–15.CrossRefGoogle ScholarPubMed
Caniggia, I., Grisaru-Gravnosky, S., Kuliszewsky, M., Post, M. and Lye, S. J. (1999). Inhibition of TGF-beta 3 restores the invasive capability of extravillous trophoblasts in preeclamptic pregnancies. J. Clin. Invest., 103, 1641–50.CrossRefGoogle ScholarPubMed
Caniggia, I., Mostachfi, H., Winter, J., et al. (2000). Hypoxia-inducible factor-1 mediates the biological effects of oxygen on human trophoblast differentiation through TGFbeta(3). J. Clin. Invest., 105, 577–87.CrossRefGoogle Scholar
Cartwright, J. E., Holden, D. P. and Whitley, G. S. (1999). Hepatocyte growth factor regulates human trophoblast motility and invasion: a role for nitric oxide. Br. J. Pharmacol., 128, 181–9.CrossRefGoogle ScholarPubMed
Cartwright, J. E., Kenny, L. C., Dash, P. R., et al. (2002). Trophoblast invasion of spiral arteries: a novel in vitro model. Placenta, 23, 232–5.CrossRefGoogle ScholarPubMed
Chen, C. P. and Aplin, J. D. (2003). Placental extracellular matrix: gene expression, deposition by placental fibroblasts and the effect of oxygen. Placenta, 24, 316–25.CrossRefGoogle ScholarPubMed
Choy, M. Y. and Manyonda, I. T. (1998). The phagocytic activity of human first trimester extravillous trophoblast. Hum. Reprod., 13, 2941–9.CrossRefGoogle ScholarPubMed
Choy, M. Y., St Whitley, G. and Manyonda, I. T. (2000). Efficient, rapid and reliable establishment of human trophoblast cell lines using poly-L-ornithine. Early Pregnancy, 4, 124–43.Google ScholarPubMed
Cockell, A. P., Learmont, J. G., Smarason, A. K., Redman, C. W., Sargent, I. L. and Poston, L. (1997). Human placental syncytiotrophoblast microvillous membranes impair maternal vascular endothelial function. Br. J. Obstet. Gynaecol., 104, 235–40.CrossRefGoogle ScholarPubMed
Copeman, J., Han, R. N., Caniggia, I., McMaster, M., Fisher, S. J. and Cross, J. C. (2000). Posttranscriptional regulation of human leukocyte antigen G during human extravillous cytotrophoblast differentiation. Biol. Reprod., 62, 1543–50.CrossRefGoogle Scholar
Crocker, I. P., Barratt, S., Kaur, M. and Baker, P. N. (2001a). The in-vitro characterization of induced apoptosis in placental cytotrophoblasts and syncytiotrophoblasts. Placenta, 22, 822–30.CrossRefGoogle Scholar
Crocker, I. P., Strachan, B. K., Lash, G. E., Cooper, S., Warren, A. Y. and Baker, P. N. (2001b). Vascular endothelial growth factor but not placental growth factor promotes trophoblast syncytialization in vitro. J. Soc. Gynecol. Invest., 8, 341–6.CrossRefGoogle Scholar
Crocker, I. P., Wareing, M., Ferris, G. R.et al. (2005). The effect of vascular origin, oxygen and tumour necrosis factor alpha on trophoblast invasion of matenal arteries in vitro. J. Pathol., 206, 476–85.CrossRefGoogle Scholar
Damsky, C. H., Librach, C., Lim, K. H., et al. (1994). Integrin switching regulates normal trophoblast invasion. Development, 120, 3657–66.Google ScholarPubMed
Di Santo, S., Malek, A., Sager, R., Andres, A. C. and Schneider, H. (2003). Trophoblast viability in perfused term placental tissue and explant cultures limited to 7–24 hours. Placenta, 24, 882–94.CrossRefGoogle ScholarPubMed
Douglas, G. C. and King, B. F. (1990). Differentiation of human trophoblast cells in vitro as revealed by immunocytochemical staining of desmoplakin and nuclei. J. Cell Sci., 96, 131–41.Google ScholarPubMed
Dunk, C., Petkovic, L., Baczyk, D., Rossant, J., Winterhager, E. and Lye, S. (2003). A novel in vitro model of trophoblast-mediated decidual blood vessel remodeling. Lab. Invest., 83(12), 1821–8.CrossRefGoogle ScholarPubMed
Dutta-Roy, A. K. (2000). Transport mechanisms for long-chain polyunsaturated fatty acids in the human placenta. Am. J. Clin. Nutr., 71, 315S–22S.CrossRefGoogle ScholarPubMed
Dye, J. F., Jablenska, R., Donnelly, J. L., et al. (2001). Phenotype of the endothelium in the human term placenta. Placenta, 22, 32–43.CrossRefGoogle ScholarPubMed
Dye, J. F., Vause, S., Johnston, T., et al. (2003). Characterization of cationic amino acid transporters and expression of endothelial nitric oxide synthase in human placental microvascular endothelial cells. FASEB J., 3, 3.Google Scholar
Fox, H. (1997). Aging of the placenta. Arch. Dis. Child. Fetal. Neonatal Ed., 77, F171–5.CrossRefGoogle ScholarPubMed
Frank, H. G., Gunawan, B., Ebeling-Stark, I., et al. (2000). Cytogenetic and DNA-fingerprint characterization of choriocarcinoma cell lines and a trophoblast/choriocarcinoma cell hybrid. Cancer Genet. Cytogenet., 116, 16–22.CrossRefGoogle Scholar
Fukushima, K., Miyamoto, S., Komatsu, H., et al. (2003). TNFalpha-induced apoptosis and integrin switching in human extravillous trophoblast cell line. Biol. Reprod., 68, 1771–8.CrossRefGoogle ScholarPubMed
Gallery, E. D., Campbell, S., Arkell, J., Nguyen, M. and Jackson, C. J. (1999). Preeclamptic decidual microvascular endothelial cells express lower levels of matrix metalloproteinase-1 than normals. Microvasc. Res., 57, 340–6.CrossRefGoogle ScholarPubMed
Gallery, E. D., Rowe, J., Schrieber, L. and Jackson, C. J. (1991). Isolation and purification of microvascular endothelium from human decidual tissue in the late phase of pregnancy. Am. J. Obstet. Gynecol., 165, 191–6.CrossRefGoogle ScholarPubMed
Garcia-Lloret, M. I., Morrish, D. W., Wegmann, T. G., Honore, L., Turner, A. R. and Guilbert, L. J. (1994). Demonstration of functional cytokine-placental interactions: CSF-1 and GM-CSF stimulate human cytotrophoblast differentiation and peptide hormone secretion. Exp. Cell Res., 214, 46–54.CrossRefGoogle ScholarPubMed
Genbacev, O., Joslin, R., Damsky, C. H., Polliotti, B. M. and Fisher, S. J. (1996). Hypoxia alters early gestation human cytotrophoblast differentiation/invasion in vitro and models the placental defects that occur in preeclampsia. J. Clin. Invest., 97, 540–50.CrossRefGoogle ScholarPubMed
Goffin, F., Munaut, C., Malassine, A., et al. (2003). Evidence of a limited contribution of feto-maternal interactions to trophoblast differentiation along the invasive pathway. Tiss. Antig., 62, 104–16.CrossRefGoogle ScholarPubMed
Gratton, R. J., Gandley, R. E., Genbacev, O., McCarthy, J. F., Fisher, S. J. and McLaughlin, M. K. (2001). Conditioned medium from hypoxic cytotrophoblasts alters arterial function. Am. J. Obstet. Gynecol., 184, 984–90.CrossRefGoogle ScholarPubMed
Guilbert, L. J., Winkler-Lowen, B., Sherburne, R., Rote, N. S., Li, H. and Morrish, D. W. (2002). Preparation and functional characterization of villous cytotrophoblasts free of syncytial fragments. Placenta, 23, 175–83.CrossRefGoogle ScholarPubMed
Haigh, T., Chen, C., Jones, C. J. and Aplin, J. D. (1999). Studies of mesenchymal cells from 1st trimester human placenta: expression of cytokeratin outside the trophoblast lineage. Placenta, 20, 615–25.CrossRefGoogle ScholarPubMed
Hall, C. S., James, T. E., Goodyer, C., Branchaud, C., Guyda, H. and Giroud, C. J. (1977). Short term culture of human midterm and term placenta: parameters of hormonogenesis. Steroids, 30, 569–80.CrossRefGoogle ScholarPubMed
Handwerger, S. and Aronow, B. (2003). Dynamic changes in gene expression during human trophoblast differentiation. Recent Prog. Horm. Res., 58, 263–81.CrossRefGoogle ScholarPubMed
Harris, L. K., Keogh, R. J., Wareing, M., et al. (2006). Invasive trophoblasts stimulate vascular smooth muscle cell apoptosis by a Fas ligand-dependent mechanism. Am. J. Pathol., 169, 1853–74.CrossRefGoogle ScholarPubMed
Hemberger, M., Cross, J. C., Ropers, H. H., Lehrach, H., Fundele, R. and Himmelbauer, H. (2001). UniGene cDNA array-based monitoring of transcriptome changes during mouse placental development. Proc. Natl Acad. Sci. USA, 98, 13,126–31.CrossRefGoogle ScholarPubMed
Hemmings, D. G. and Guilbert, L. J. (2002). Polarized release of human cytomegalovirus from placental trophoblasts. J. Virol., 76, 6710–17.CrossRefGoogle ScholarPubMed
Higuchi, T., Fujiwara, H., Egawa, H., et al. (2003). Cyclic AMP enhances the expression of an extravillous trophoblast marker, melanoma cell adhesion molecule, in choriocarcinoma cell JEG3 and human chorionic villous explant cultures. Mol. Hum. Reprod., 9, 359–66.CrossRefGoogle ScholarPubMed
Hirano, T., Higuchi, T., Ueda, M., et al. (1999). CD9 is expressed in extravillous trophoblasts in association with integrin alpha3 and integrin alpha5. Mol. Hum. Reprod., 5, 162–7.CrossRefGoogle ScholarPubMed
Hoang, V. M., Foulk, R., Clauser, K., Burlingame, A., Gibson, B. W. and Fisher, S. J. (2001). Functional proteomics: examining the effects of hypoxia on the cytotrophoblast protein repertoire. Biochemistry, 40, 4077–86.CrossRefGoogle ScholarPubMed
Huch, G., Hohn, H. P. and Denker, H. W. (1998). Identification of differentially expressed genes in human trophoblast cells by differential-display RT-PCR. Placenta, 19, 557–67.CrossRefGoogle ScholarPubMed
Huppertz, B., Kingdom, J., Caniggia, I., et al. (2003). Hypoxia favours necrotic versus apoptotic shedding of placental syncytiotrophoblast into the maternal circulation. Placenta, 24, 181–90.CrossRefGoogle ScholarPubMed
Jauniaux, E., Gulbis, B. and Burton, G. J. (2003a). Physiological implications of the materno-fetal oxygen gradient in human early pregnancy. Reprod. Biomed. Online, 7, 250–3.CrossRefGoogle Scholar
Jauniaux, E., Hempstock, J., Greenwold, N. and Burton, G. J. (2003b). Trophoblastic oxidative stress in relation to temporal and regional differences in maternal placental blood flow in normal and abnormal early pregnancies. Am. J. Pathol., 162, 115–25.CrossRefGoogle Scholar
Kacemi, A., Challier, J. C., Galtier, M. and Olive, G. (1996). Culture of endothelial cells from human placental microvessels. Cell Tissue Res., 283, 183–90.CrossRefGoogle ScholarPubMed
Kadyrov, M., Schmitz, C., Black, S., Kaufmann, P. and Huppertz, B. (2003). Pre-eclampsia and maternal anaemia display reduced apoptosis and opposite invasive phenotypes of extravillous trophoblast. Placenta, 24, 540–8.CrossRefGoogle ScholarPubMed
Kalionis, B. and Moses, E. (2003). Advanced molecular techniques in pregnancy research: proteomics and genomics – a workshop report. Placenta, 24, S119–22.CrossRefGoogle ScholarPubMed
Kanayama, N., Takahashi, K., Matsuura, T., et al. (2002). Deficiency in p57Kip2 expression induces preeclampsia-like symptoms in mice. Mol. Hum. Reprod., 8, 1129–35.CrossRefGoogle ScholarPubMed
Kao, L. C., Caltabiano, S., Wu, S., Strauss, J. F. and Kliman, H. J. (1988). The human villous cytotrophoblast: interactions with extracellular matrix proteins, endocrine function, and cytoplasmic differentiation in the absence of syncytium formation. Dev. Biol., 130, 693–702.CrossRefGoogle ScholarPubMed
Karl, P. I., Alpy, K. L. and Fisher, S. E. (1992). Serial enzymatic digestion method for isolation of human placental trophoblasts. Placenta, 13, 385–7.CrossRefGoogle ScholarPubMed
Kaufmann, P., Black, S. and Huppertz, B. (2003). Endovascular trophoblast invasion: implications for the pathogenesis of intrauterine growth retardation and preeclampsia. Biol. Reprod., 69, 1–7.CrossRefGoogle ScholarPubMed
Kemp, B., Kertschanska, S., Handt, S., Funk, A., Kaufmann, P. and Rath, W. (1999). Different placentation patterns in viable compared with nonviable tubal pregnancy suggest a divergent clinical management. Am. J. Obstet. Gynecol., 181, 615–20.CrossRefGoogle ScholarPubMed
Kemp, B., Kertschanska, S., Kadyrov, M., Rath, W., Kaufmann, P. and Huppertz, B. (2002). Invasive depth of extravillous trophoblast correlates with cellular phenotype: a comparison of intra- and extrauterine implantation sites. Histochem. Cell Biol., 117, 401–14.CrossRefGoogle ScholarPubMed
Khan, S., Katabuchi, H., Araki, M., Nishimura, R. and Okamura, H. (2000). Human villous macrophage-conditioned media enhance human trophoblast growth and differentiation in vitro. Biol. Reprod., 62, 1075–83.CrossRefGoogle ScholarPubMed
Kilani, R. T., Mackova, M., Davidge, S. T. and Guilbert, L. J. (2003). Effect of oxygen levels in villous trophoblast apoptosis. Placenta, 24, 826–34.CrossRefGoogle ScholarPubMed
Kliman, H. J., Nestler, J. E., Sermasi, E., Sanger, J. M. and Strauss, J. F.. (1986). Purification, characterization, and in vitro differentiation of cytotrophoblasts from human term placentae. Endocrinology, 118, 1567–82.CrossRefGoogle ScholarPubMed
Kudo, Y., Boyd, C. A., Kimura, H., Cook, P. R., Redman, C. W. and Sargent, I. L. (2003). Quantifying the syncytialisation of human placental trophoblast BeWo cells grown in vitro. Biochim. Biophys. Acta, 1640, 25–31.CrossRefGoogle ScholarPubMed
Lacey, H., Haigh, T., Westwood, M. and Aplin, J. D. (2002). Mesenchymally-derived insulin-like growth factor 1 provides a paracrine stimulus for trophoblast migration. BMC Dev. Biol., 2, 5.CrossRefGoogle ScholarPubMed
Librach, C. L., Werb, Z., Fitzgerald, M. L., et al. (1991). 92-kD type IV collagenase mediates invasion of human cytotrophoblasts. J. Cell Biol., 113, 437–49.CrossRefGoogle ScholarPubMed
Logan, S. K., Fisher, S. J. and Damsky, C. H. (1992). Human placental cells transformed with temperature-sensitive simian virus 40 are immortalized and mimic the phenotype of invasive cytotrophoblasts at both permissive and nonpermissive temperatures. Cancer Res., 52, 6001–9.Google ScholarPubMed
Mayhew, T. M., Ohadike, C., Baker, P. N., Crocker, I. P., Mitchell, C. and Ong, S. S. (2003). Stereological investigation of placental morphology in pregnancies complicated by pre-eclampsia with and without intrauterine growth restriction. Placenta, 24, 219–26.CrossRefGoogle ScholarPubMed
Meekins, J. W., Pijnenborg, R., Hanssens, M., McFadyen, I. R. and Asshe, A. (1994). A study of placental bed spiral arteries and trophoblast invasion in normal and severe pre-eclamptic pregnancies. Br. J. Obstet. Gynaecol., 101, 669–74.CrossRefGoogle ScholarPubMed
Myers, J., Macleod, M., Reed, B., Harris, N., Mires, G. and Baker, P. (2004). Use of proteomic patterns as a novel screening tool in pre-eclampsia. J. Obstet. Gynaecol., 24, 873–4.CrossRefGoogle ScholarPubMed
Naicker, T., Khedun, S. M., Moodley, J. and Pijnenborg, R. (2003). Quantitative analysis of trophoblast invasion in preeclampsia. Acta Obstet. Gynecol. Scand., 82, 722–9.CrossRefGoogle ScholarPubMed
Page, N. M., Kemp, C. F., Butlin, D. J. and Lowry, P. J. (2002). Placental peptides as markers of gestational disease. Reproduction, 123, 487–95.CrossRefGoogle ScholarPubMed
Parast, M. M., Aeder, S. and Sutherland, A. E. (2001). Trophoblast giant-cell differentiation involves changes in cytoskeleton and cell motility. Dev. Biol., 230, 43–60.CrossRefGoogle ScholarPubMed
Pijnenborg, R., D'Hooghe, T., Vercruysse, L. and Bambra, C. (1996). Evaluation of trophoblast invasion in placental bed biopsies of the baboon, with immunohistochemical localisation of cytokeratin, fibronectin, and laminin. J. Med. Primatol., 25, 272–81.CrossRefGoogle ScholarPubMed
Pijnenborg, R., Robertson, W. B., Brosens, I. and Dixon, G. (1981). Review article: trophoblast invasion and the establishment of haemochorial placentation in man and laboratory animals. Placenta, 2, 71–91.CrossRefGoogle ScholarPubMed
Potgens, A. J., Kataoka, H., Ferstl, S., Frank, H. G. and Kaufmann, P. (2003). A positive immunoselection method to isolate villous cytotrophoblast cells from first trimester and term placenta to high purity. Placenta, 24, 412–23.CrossRefGoogle ScholarPubMed
Redline, R. W. and Patterson, P. (1995). Pre-eclampsia is associated with an excess of proliferative immature intermediate trophoblast. Hum. Pathol., 26, 594–600.CrossRefGoogle ScholarPubMed
Reimer, T., Koczan, D., Gerber, B., Richter, D., Thiesen, H. J. and Friese, K. (2002). Microarray analysis of differentially expressed genes in placental tissue of pre-eclampsia: up-regulation of obesity-related genes. Mol. Hum. Reprod., 8, 674–80.CrossRefGoogle ScholarPubMed
Reister, F., Frank, H. G., Kingdom, J. C., et al. (2001). Macrophage-induced apoptosis limits endovascular trophoblast invasion in the uterine wall of preeclamptic women. Lab. Invest., 81, 1143–52.CrossRefGoogle ScholarPubMed
Sacks, G. P., Clover, L. M., Bainbridge, D. R., Redman, C. W. and Sargent, I. L. (2001). Flow cytometric measurement of intracellular Th1 and Th2 cytokine production by human villous and extravillous cytotrophoblast. Placenta, 22, 550–9.CrossRefGoogle ScholarPubMed
Schutz, M., Teifel, M. and Friedl, P. (1997). Establishment of a human placental endothelial cell line with extended life span after transfection with SV40 T-antigens. Eur. J. Cell Biol., 74, 315–20.Google Scholar
Shiverick, K. T., King, A., Frank, H., Whitley, G. S., Cartwright, J. E. and Schneider, H. (2001). Cell culture models of human trophoblast II: trophoblast cell lines – a workshop report. Placenta, 22, S104–6.CrossRefGoogle ScholarPubMed
Sibley, C. P., Birdsey, T. J., Brownbill, P., et al. (1998). Mechanisms of maternofetal exchange across the human placenta. Biochem. Soc. Trans., 26, 86–91.CrossRefGoogle ScholarPubMed
Siman, C. M., Sibley, C. P., Jones, C. J., Turner, M. A. and Greenwood, S. L. (2001). The functional regeneration of syncytiotrophoblast in cultured explants of term placenta. Am. J. Physiol. Regul. Integr. Comp. Physiol., 280, R1116–22.CrossRefGoogle ScholarPubMed
Soothill, P. W., Nicolaides, K. H., Rodeck, C. H. and Campbell, S. (1986). Effect of gestational age on fetal and intervillous blood gas and acid–base values in human pregnancy. Fetal Ther., 1, 168–75.CrossRefGoogle ScholarPubMed
Tanaka, S., Kunath, T., Hadjantonakis, A. K., Nagy, A. and Rossant, J. (1998). Promotion of trophoblast stem cell proliferation by FGF4. Science, 282, 2072–5.CrossRefGoogle ScholarPubMed
Tarrade, A., Lai Kuen, R., Malassine, A., et al. (2001a). Characterization of human villous and extravillous trophoblasts isolated from first trimester placenta. Lab. Invest., 81, 1199–211.CrossRefGoogle Scholar
Tarrade, A., Schoonjans, K., Pavan, L., et al. (2001b). PPARgamma/RXRalpha heterodimers control human trophoblast invasion. J. Clin. Endocrinol. Metab., 86, 5017–24.Google Scholar
Vicovac, L. and Aplin, J. D. (1996). Epithelial–mesenchymal transition during trophoblast differentiation. Acta Anat. (Basel), 156, 202–16.Google ScholarPubMed
Vicovac, L., Jones, C. J. and Aplin, J. D. (1995). Trophoblast differentiation during formation of anchoring villi in a model of the early human placenta in vitro. Placenta, 16, 41–56.CrossRefGoogle Scholar
Dadelszen, P., Hurst, G. and Redman, C. W. (1999). Supernatants from co-cultured endothelial cells and syncytiotrophoblast microvillous membranes activate peripheral blood leukocytes in vitro. Hum. Reprod., 14, 919–24.CrossRefGoogle Scholar
Watson, A. L., Palmer, M. E., et al. (1995). Human chorionic gonadotrophin release and tissue viability in placental organ culture. Hum. Reprod., 10, 2159–64.CrossRefGoogle ScholarPubMed
Wetzka, B., Clark, D. E., Charnock-Jones, D. S., Zahradnik, H. P. and Smith, S. K. (1997). Isolation of macrophages (Hofbauer cells) from human term placenta and their prostaglandin E2 and thromboxane production. Hum. Reprod., 12, 847–52.CrossRefGoogle ScholarPubMed
Yui, J., Garcia-Lloret, M., Brown, A. J., et al. (1994). Functional, long-term cultures of human term trophoblasts purified by column-elimination of CD9 expressing cells. Placenta, 15, 231–46.CrossRefGoogle ScholarPubMed
Zybina, T. G., Kaufmann, P., Frank, H. G., Freed, J., Kadyrov, M. and Biesterfeld, S. (2002). Genome multiplication of extravillous trophoblast cells in human placenta in the course of differentiation and invasion into endometrium and myometrium. I. Dynamics of polyploidization. Tsitologiia, 44, 1058–67.Google ScholarPubMed

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