Abstract
In the human, fetal cytotrophoblastic cells play a key role in the implantation process and in placental development. With the progression of placentation, two pathways of differentiation lead to the formation of two distinct phenotypes. In the villous trophoblast (fusion phenotype), the trophblast differentiates from the fusion of mononuclear cytotrophoblastic cells into a syncytium, the syncytiotrophoblast. Bathing the maternal blood, the syncytiotrophoblast is involved in maternal-fetal exchanges and in placental endocrine functions. In the extravillous trophoblast (proliferative/invasive phenotype), the cytotrophoblastic cells proliferate and migrate into the decidua, remodeling the pregnant endometrium and its vasculature. This review summarizes our current knowledge of the key step of villous differentiation—the cell-cell fusion of the cytotrophoblastic cells—and on the invasion process of extravillous trophoblast. Experimental evidence demonstrates that the genetic differentiation/invasion programs of cytotrophoblastic cells could be modulated by their environment: oxygen, extracellular matrix, and soluble factors (cytokines, growth factors, and hormones). Cytotrophoblastic cells fusion and the functional differentiation of villous trophoblast are specifically stimulated by estradiol, glucocorticoids, and human chorionic gonadotropin (hCG) whereas progesterone is ineffective. Because these hormones are temporally secreted in large amounts and present at the fetomaternal interface, they are in good position to play a physiologic role in trophoblast differentiation. hCG may be important very early in pregnancy, when production of this glycoprotein is maximal, whereas estrogen increasingly produced by the fetoplacental unit and cortisol secreted from the fetal adrenal may be implicated in the end-stage maturation and aging of the trophoblast.
Similar content being viewed by others
References
Benirschke, K. and Kaufmann, P. (2000). In: Pathology of the human placenta. Benirschke, K. and Kaufmann, P. (eds.). Springer-Verlag: New York.
Zhou, Y., Damsky, C. H., and Fisher, S. J. (1997). J. Clin. Invest. 99, 2152–2164.
Richard, R. (1961). Proc. Soc. Exp. Biol. Med. 106, 829–831.
Kliman, H. J., Nestler, J. E., Sermasi, E., Sanger, J. M., and Strauss, J. (1986). Endocrinology 118, 1567–1582.
Mayhew, T. M. (2001). Histol. Histopathol. 16, 1213–1224.
Roulier, S., Rochette-Egly, C., Rebut-Bonneton, C., Porquet, D., and Evain-Brion, D. (1994). Mol. Cell. Endocrinol. 105, 165–173.
Cronier, L., Dubut, A., Guibourdenche, J., and Malassiné, A. (1999). Trophobl. Res. 13, 69–86.
Cronier, L., Bastide, B., Defamie, N., Niger, C., Pointis, G., Gasc, J. M., and Malassiné, A. (2001). Histol. Histopathol. 16, 285–295.
Cronier, L., Hervé, J. C., Délèze, J., and Malassiné, A. (1997). Microsc. Res. Tech. 38, 21–28.
Frendo, J. L., Guibourdenche, J., Vidaud, M., Evain-Brion, D., and Malassiné, A. (2001). Placenta 22, A22.
Adler, R. R., Ng, A. K., and Rote, N. S. (1995). Biol. Reprod. 53, 905–910.
Huppertz, B., Tews, D., and Kaufmann, P. (2001). Int. Rev. Cytol. 205, 215–253.
Harris, J. R. (1998). BioEssays 20, 307–316.
Rote, N. S., Lin, L., and Xu, B. (1998). Trophobl. Res. 12, 315–328.
Mi, S., Lee, X. O., Veldman, G. M., Finnerthy, H., Racie, L., LaVaillie, E., Tang, X. Y., Edouard, P., Howes, S., Keith, J. C., and McCoy, J. (2000). Nature 403, 785–788.
Aronow, B., J., Richardson, B. D., and Handwerger, S. (2001). Physiol. Genomics 6, 105–116.
Douglas, G. C. and King, B. F. (1990). J. Cell Sci. 96, 131–141.
Keryer, G., Alsat, E., Tasken, K., and Evain-Brion, D. (1998). J. Cell Sci. 111, 995–1004.
Cronier, L., Bastide, B., Hervé, J. C., Délèze, J., and Malassiné, A. (1994). Endocrinology 135, 402–408.
Richards, R. G., Hartman, S. M., and Handwerger, S. (1994). Endocrinology 135, 321–329.
Tarrade, A., Lai Kuen, R., Malassiné, A., Tricottet, V., Blain, P., Vidaud, M., and Evain-Brion, D. (2001). Lab. Invest. 81, 1199–1211.
Frendo, J. L., Thérond, P., Bird, T., Massin, N., Muller, F., Guibourdenche, J., Luton, D., Vidaud, M., Anderson, W., and Evain-Brion, D. (2001). Endocrinology 142, 3638–3648.
Morrish, D. W., Linetsky, E., Bhardwaj, D., Li, H., Dakour, J., Marsh, R. G., Paterson, M. C., and Godbout, R. (1996). Placenta 17, 431–441.
Stephanou, A. and Handwerger, S. (1995). Biophys. Res. Commun. 206, 215–222.
Petraglia, F., Florio, P., Nappi, C., and Genazzani, A. R. (1996). Endocr. Rev. 17, 156–186.
Islami, D., Chardonnens, D., Campana, A., and Bischof, P. (2001). Mol. Hum. Reprod. 7, 3–9.
Tarrade, A., Schoonjans, K., Guibourdenche, J., Bidart, J., Vidaud, M., Auwerx, J., Rochette-Egly, C., and Evain-Brion, D. (2001). Endocrinology 142, 4504–4514.
Kao, L. C., Caltabiano, S., Wu, S., Strauss III, J. F., and Kliman, H. J. (1988). Dev. Biol. 130, 693–702.
Morrish, D. W., Bhardwaj, D., Dabbag, L. K., Marusyk, H., and Siy, O. (1987). J. Clin. Endocrinol. Metab. 65, 1282–1290.
Henson, M. C., Shi, W., Green, S. J., and Reggio, B. (1996). Endocrinology 137, 2067–2074.
Alsat, E., Haziza, J., and Evain-Brion, D. (1993). J. Cell Physiol. 154, 122–128.
Garcia-Lloret, M. J., Morrish, D. W., Wegmann, T. G., Honore, L., Truner, A. R., and Guilbert, L. J. (1994). Exp. Cell. Res. 214, 46–54.
Cervar, M., Blaschitz, A., Dohr, G., and Desoye, G. (1999). Cell Tissue Res. 295, 297–305.
Khan, S., Katabuchi, H., Araki, M., Nishimura, R., and Okamara, H. (2000). Biol. Reprod. 62, 1075–1083.
Crocker, I. P., Strachan, B. K., Lash, G. E., Cooper, S., Warren, A. Y., and Baker, P. N. (2001). J. Soc. Gynecol. Invest. 8, 341–346.
Morrish, D. W., Bhardwaj, D., and Paras, M. T. (1991). Endocrinology 129, 22–26.
Cronier, L., Alsat, E., Hervé, J. C., Délèze, J., and Malassiné, A. (1997). Trophobl. Res. 10, 377–391.
Nachtigall, M. J., Kliman, H. J., Feinberg, R. F., Olive, D. L., Engin, O., and Arici, A. (1996). J. Clin. Endocrinol. Metab. 81, 1282–1290.
Schaiff, W. T., Carlson, M. G., Smith, S. D., Levy, R., Nelson, D. M., and Sadovsky, Y. (2000). J. Clin. Endocrinol. Metab. 85, 3874–3881.
Alsat, E., Wyplosz, P., Malassiné, A., Guibourdenche, J., Porquet, D., Nessmann, C., and Evain-Brion, D. (1996). J. Cell Physiol. 168, 346–353.
Levy, R., Smith, S. D., Chandler, K., Sadovsky, Y., and Nelson, D. M. (2000). Am. J. Physiol. Cell Physiol. 278, C982-C988.
Jameson, J. L. and Hollenberg, A. N. (1993). Endocr. Rev. 14, 203–221.
Srisuparp, S., Strakova, Z., and Fazleabas, A. T. (2001). Arch. Med. Res. 32, 627–634.
Rao, C. V. (1996). J. Physiol. Pharmacol. 47, 41–53.
Licht, P., Russu, V., and Wildt, L. (2001). Semin. Reprod. Med. 19, 37–47.
Shi, Q. J., Lei, Z. M., Rao, C. V., and Lin, J. (1993). Endocrinology 132, 1397–1395.
Licht, P., Cao, H., Lei, Z. M., Rao, C. V., and Merz, W. E. (1993). Endocrinology 133, 1014–1025.
Pepe, G. J. and Albrecht, E. D. (1995). Endocr. Rev. 16, 608–648.
Alsat, E., Malassiné, A., and Cedard, L. (1991). Trophobl. Res. 5, 127–149.
Lafond, J., Charest, M. C., Alain, J. F., Brissette, L., Masse, A., Robidoux, J., and Simoneau, S. (1999). Placenta 20, 583–590.
Grimes, R. W., Pepe, G. I., and Albrecht, E. D. (1996). J. Clin. Endocrinol. Metab. 81, 2675–2679.
Billiar, R. B., Pepe, G. J., and Albrecht, E. D. (1997). Placenta 18, 365–370.
Merz, W. (1996). Eur. J. Endocrinol. 135, 269–284.
Omigbodun, A., Ziolkiewicz, P., Tessier, P., Hoyer, J. R., and Coutifaris, C. (1997). Endocrinology 138, 4308–4315.
Karalis, K., Goodwin, G., and Majzoub, J. A. (1996). Nat. Med. 2, 556–560.
Rossmanith, W. G., Wolfarhrt, S., Ecker, A., and Eberhart, E. (1997). Horm. Metab. Res. 29, 604–610.
Cronier, L., Guibourdenche, J., Niger, C., and Malassiné, A. (1999). Placenta 20, 669–676.
Babischkin, J. S., Burleigh, D. W., Mayhew, T. M., Pepe, G. J., and Albrecht, E. D. (2001). Placenta 22, 276–283.
Ringler, G. E., Kallen, C. B., and Strauss III, J. F. (1989). Endocrinology 124, 1625–1631.
Guller, S., Wozniak, R., Krikun, G., Burnham, J. M., Kaplan, P., and Lockwood, J. (1993). Endocrinology 133, 1139–1146.
Ryu, J. S., Maleska, R. J., LaChapelle, L., and Guller, S. (1999). Endocrinology 140, 3904–3908.
Jones, S. A., Brooks, A. N., and Challis, J. R. (1989). J. Clin. Endocrinol. Metab. 68, 825–830.
Cronier, L., Alsat, E., Hervé, J. C., Délèze, J., and Malassiné, A. (1998). Trophobl. Res. 11, 35–49.
Winterhager, E., von Ostau, C., Gerke, M., Gruemmer, M., Traub, O., and Kaufmann, P. (1999). Placenta 20, 627–638.
Damsky, C. H., Librach, C., Lim, K. H., Fitzgerald, M. L., McMaster, M. T., Janatpour, M., Zhou, Y., Logan, S. K., and Fisher, S. J. (1994). Development 120, 3657–3666.
Vicovac, L. and Aplin, D. (1996). Acta Anat. 156, 202–216.
Janatpour, M. J., McMaster, M. T., Genbacev, O., Zhou, Y., Dong J. Y., Cross, J. C., Israel, M. A., and Fisher, S. J. (2000). Development 127, 540–558.
Westerman, B. A., Poutsma, A., Maruyama, K., Schrijnemakers, H. F. J., van Wijk, I. J., and Oudejans, C. B. M. (2002). Mech. Dev. 113, 85–90.
Polette, M., Nawrocki, B., Pintiaux, A., Massenat, C., Maquoi, E., Volders, L., Schaaps, J. P., Birembaut, P., and Foidart, J. M. (1994). Lab. Invest. 71, 838–845.
Bischof, P., Haenggeli, L., and Campana, A. (1995). Hum. Reprod. 10, 734–742.
Lala, P. K., Hamilton, G. S., and Athanassiades, A. (1998). Trophobl. Res. 12, 327–339.
Bischof, P., Meisser, A., and Campana, A. (2000). Trophobl. Res. 14, 56–60.
Tarrade, A., Schoonjans, K., Pavan, L., Auwerx, J., Rochette-Egly, C., Evain-Brion, D., and Fournier, T. (2001). Endocrinology 86, 5017–5024.
Burton, G. J., Jauniaux, E., and Watson, A. L. (1999). Am. J. Obstet. Gynecol. 181, 718–724.
Aplin, J. D., Haigh, T., Jones, C. J. P., Church, H. J., and Vicovac, L. J. (1999). Biol. Reprod. 60, 828–838.
Genbacev, O., Zhou, Y., Ludlow, J. W., and Fisher, S. J. (1997). Science 277, 1660–1672.
Caniggia, I., and Winter, J. L. (2002). Trophobl. Res. 16, 47–57.
Shimonovitz, S., Hurwitz, A., Hochner-Celnikier, D., Dushnik, M., Anteby, E., and Yagel, S. (1998). Am. J. Obstet. Gynecol. 178, 457–461.
Castellucci, M., De Matteis, R., Meisser, A., Cancello, R., Monsurro, V., Islami, D., Sarzini, R., Marzioni, D., Cinti, S., and Bischof, P. (2000). Mol. Hum. Reprod. 6, 951–958.
Gonzalez, R. R., Devoto, L., Campana, A., and Bischof, P. (2001). Endocrine 15, 157–164.
Tao, Y. X., Lei, Z. M., Hofmann, G. E., and Rao, C. V. (1995). Biol. Reprod. 53, 899–904.
Yagel, S., Geva, T. E., Solomon, H., Shimonovitz, S., Reich, R., Finci-Ycheskel, Z., Mayer, M., and Milwidsky, A. (1993). J. Clin. Endocrinol. Metab. 77, 1506–1511.
Zygmunt, M., Hahn, D., Kiesenbauer, N., Munstedt, K., and Lang, U. (1998). Am. J. Reprod. Immunol. 40, 326–331.
Majzoub, J. A. and Karalis, K. P. (1999). Am. J. Obstet. Gynecol. 180, 42–46.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Malassiné, A., Cronier, L. Hormones and human trophoblast differentiation. Endocr 19, 3–11 (2002). https://doi.org/10.1385/ENDO:19:1:3
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1385/ENDO:19:1:3