Abstract
The localisation of insulin receptors (IR) was investigated on cryosections of human non-pathologic first trimester and full term placentae by indirect immunohistochemistry with three different monoclonal antibodies (MABS). In placentae from 6 to 10 weeks post-menstruation (p-m.), only syncytiotrophoblast was stained, predominantly that of mesenchymal villi and syncytial sprouts, which are areas of high proliferative activity. In placentae from 11 to 14 weeks p-m., endothelial cells commenced to react with the IR MABS and the syncytiotrophoblast was less intensely labelled than at weeks 6 to 10 p-m. In term placentae, the microvillous membrane of the syncytiotrophoblast showed only patches of weak immunoreactivity. In contrast, the endothelial cells in the placenta but not in the umbilical cord were strongly stained. The amniotic epithelium in the chorionic plate and fibroblasts in the stroma were conspicuously labelled. The data indicate: (1) the receptor density on villous syncytiotrophoblast decreases and that of fetal endothelium increases throughout gestation; (2) syncytiotrophoblast of human term placentae expresses a low level per unit area of surface IR; and (3) the majority of IR in human term placentae is located in fetal endothelium. Apart from yet unknown functional effects of maternal and fetal insulin at the placental barrier, the results suggest a growth promoting effect on the trophoblast of maternal insulin in first trimester as well as developmental effects of fetal insulin on the feto-placental vessels at term.
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References
Adam PAJ, Teramo K, Raiha N, Gitlin D, Schwartz R (1969) Human fetal insulin metabolism early in gestation. Response to acute elevation of the fetal glucose concentration and placental transfer of human insulin 131I. Diabetes 18: 409–416
Aoki Y (1991) Effects of various growth factors on the growth of trophoblast cells in long-term culture. Acta Obstet Gynaecol Jpn 43: 627–632
Bacon BJ, Gilbert RD, Kaufmann P, Smith AD, Trevino FT, Longo LD (1984) Placental anatomy and diffusing capacity in guinea pigs following long-term maternal hypoxia. Placenta 5: 474–488
Bar RS, Hoak JC, Peacock ML (1978) Insulin receptors in human endothelial cells: identification and characterization. J Clin Endocrinol Metab 47: 699–702
Baron V, Gautier N, Komriya A, Hainaut P, Scimeca JC, Mervic M, Lavielle S, Dolais-Kitabgi J, Van Oberghen E (1990) Insulin binding to its receptor induces a conformational change in the receptor C-terminus. Biochemistry 29: 4634–4641
Benirschke K, Kaufmann P (1990) Pathology of the human placenta, 2nd edn. Springer; New York, pp 81–113
Castellucci M, Scheper M, Scheffen I, Celona A, Kaufmann P (1990) The development of the human placental villous tree. Anat Embryol 181: 117–128
Challier JC, Hauguel S, Desmaizieres V (1986) Effect of insulin on glucose uptake and metabolism in the human placenta. J Clin Endocrinol Metab 62: 803–807
Civin CI, Trischmann TM, Fackler MJ, Bernstein ID, Bühring HG, Campos L, Greaves MF, Kamoun M, Katz DR, Lansdorp PM, Look AT, Seed B, Sutherland DR, Tindle RW, Uchanska-Ziegler B (1989) Report on the CD34 cluster workshop. In: Knopp W (ed) Leucocyte typing IV. Oxford University Press, Oxford, pp 818–825
Desoye G, Weiss PAM (1987) Influence of the lipid environment on insulin binding to placental membranes from normal and diabetic mothers. Trophoblast Res 2: 29–43
Desoye G, Schweditsch MO, Pfeiffer KP, Zechner R, Kostner GM (1987) Correlation of hormones with lipid and lipoprotein levels during normal pregnancy and post partum. J Clin Endocrinol Metab 64: 704–712
Desoye G, Hofmann HMH, Weiss PAM (1992) Insulin binding to trophoblast plasma membranes and placental glycogen content in well-controlled gestational diabetic woman treated with diet or insulin, in well-controlled overt diabetic patients and in healthy control subjects. Diabetologia 35: 45–55
Douglas GC, King BF (1990) Differentiation of human trophoblast cells in vitro as revealed by immunocytochemical staining of desmoplakin and nuclei. J Cell Sci 96: 131–141
Duronio V, Jacobs S (1988) Comparison of insulin and IGF-I receptors. In: Venter JC, Harrison LC (eds) Receptor biochemistry and methodology, vol 12B. Liss, New York, pp 3–18
Fletcher JM, Falconer J, Bassett JM (1982) The relationship of body and placental weight to plasma levels of insulin and other hormones during development in fetal rabbits. Diabetologia 23: 124–130
Forsayeth J, Caro JF, Sinha MK, Maddoux BA, Goldfine ID (1987a) Monoclonal antibodies to the human insulin receptor that activate glucose transport but not insulin receptor kinase activity. Proc Natl Acad Sci USA 84: 3448–3451
Forsayeth J, Montemurro A, Maddux BA, DePirro R, Goldfine ID (1987b) Effect of monoclonal antibodies on human insulin receptor autophosphorylation, negative cooperativity, and down-regulation. J Biol Chem 262: 4134–4140
Fujita-Yamaguchi Y, Choi S, Sakamoto Y, Itakura K (1983) Purification of insulin receptor with full binding activity. J Biol Chem 258: 5045–5049
Gautier N, Alengrin F, Ponzio G, Rossi B, Dolais-Kitabgi J (1986) Etude des fonctions du recepteur de l'insuline a l'aide d'anticorps monoclonaux anti-recepteur. Ann Endocrinol 47: 215 (Abstr)
Jonas HA, Cox AJ, Harrison LC (1989) Delineation of atypical insulin receptors from classical insulin and Type I insulin-like growth factors in human placenta. Biochem J 257: 101–107
Jones CJ, Hartmann M, Blaschitz A, Desoye G (1993) Ultrastructural localization of insulin receptors in human placenta. Am J Reprod Immunol 30: 136–145
Kaufmann P, Luckhardt M, Leiser R (1988) Three-dimensional representation of the fetal vessel system in the human placenta. Trophoblast Res 3: 113–137
King GL, Buzney S, Kahn CR, Hetu N, Buchwald S, MacDonald SG, Rand LI (1983) Differential responsiveness to insulin of endothelial and support cells from micro- and macrovessels. J Clin Invest 71: 974–979
Ladines-Llave CA, Maruo T, Manalo AS, Mochizuki M (1991) Cytologic localization of epidermal growth factor and its receptor in developing human placenta varies over the course of pregnancy. Am J Obstet Gynecol 165: 1377–1382
Lang I, Hartmann M, Blaschitz A, Dohr G, Skofitsch G, Desoye G (1993) Immunohistochemical evidence for the heterogeneity of maternal and fetal vascular endothelial cells in human full term placenta. Cell Tissue Res 274: 211–218
Milazzo G, Yip CC, Maddux BA, Vigneri R, Goldfine ID (1992) High-affinity insulin binding to an atypical insulin-like growth factor-I receptor in human breast cancer cells. J Clin Invest 89: 899–908
Morgan DO, Roth RA (1986) Mapping surface structures of the human insulin receptor with monoclonal antibodies: localization of main immunogenic regions to the receptor kinase domain. Biochemistry 25: 1364–1371
Morgan DO, Ho L, Korn L, Roth RA (1986) Insulin action is blocked by a monoclonal antibody that inhibits insulin receptor kinase. Proc Natl Acad Sci USA 83: 328–332
Morrish DW, Bhardwaj D, Dabbagh LK, Marusyk H, Siy O (1987) Epidermal growth factor induces differentiation and secretion of human chorionic gonadotropin and placental lactogen in normal human placenta. J Clin Endocrinol Metab 65: 1282–1290
Mosthaf L, Grako K, Dull TJ, Coussens L, Ullrich A, McClain DA (1990) Functionally distinct insulin receptors generated by tissue-specific alternative splicing. EMBO J 9: 2409–2413
Mühlhauser J, Crescimanno C, Kaufmann P, Höfler H, Zaccheo D, Castellucci M (1993) Differentiation and proliferation patterns in human trophoblast revealed by c-erbB-2 oncogene product and EGF-R. J Histochem Cytochem 41: 165–173
Nelson DM, Smith RM, Jarett L (1978) Non-uniform distribution and grouping of the insulin receptors on the surface of human placental syncytical trophoblast. Diabetes 27: 530–538
Scheffen I, Kaufman P, Philippens L, Leiser R, Geisen C, Mottaghy K (1990) Alterations of the fetal capillary bed in the guinea pig placenta following long-term hypoxia. In: Piiper J, Goldstick TK, Meyer D (eds) Oxygen transfer to tissue, XII. Plenum Press, New York, pp 779–790
Schmon B, Hartmann M, Jones CJ, Desoye G (1991) Insulin and glucose do not affect the glycogen content in isolated and cultured trophoblast cells of human term placenta. J Clin Endocrinol Metab 73: 888–893
Seino S, Seino M, Nishi S, Bell GI (1989) Structure of the human insulin receptor gene and characterization of its promoter. Proc Natl Acad Sci USA 86: 114–118
Soos MA, Siddle K (1989) Immunological relationships between receptors for insulin and insulin-like growth factor. I. Biochem J 263: 553–563
Stagstedt J, Reaven GM, Hansen T, Goldstein A, Olsson L (1990) Regulation of insulin receptor functions by a peptide derived from a major histocompatibility complex class I antigen. Cell 62: 297–307
Strauss DS (1984) Growth-stimulatory actions of insulin in vitro and in vivo. Endocrine Rev 5: 356–369
Susa JB, McCormick KL, Widess JA, Singer DB, Adamsons K, Schwartz R (1979) Chronic hyperinsulinemia in the fetal rhesus monkey. Diabetes 28:1058–1063
Tavare JM, Holmes CH (1989) Differential expression of the receptors for epidermal growth factor and insulin in the developing human placenta. Cell Signall 1: 55–64
Thomas CR, Eriksson G, Eriksson UJ (1990) Effects of maternal diabetes on placental transfer of glucose in rats. Diabetes 39: 276–282
Whitsett JA, Lessard JL (1978) Characteristics of the microvillous brush border of human placenta: insulin receptor localization in brush border membranes. Endocrinology 103: 1458–1468
Yanaihara N, Yanaihara C, Iguchi K, Inoue T, Toyoshige M, Mochizuki T, Hoshino M, Kurokawa N, Kaneko T (1989) Demonstration of two distinct insulin-binding components in solubilized human placental membranes by radioimmunoassay using synthetic peptide and anti-synthetic peptide antibody. Diab Res Clin Pract 7:S109-S113
Young M, Stern MDR, Horn J, Noakes DE (1982) Protein synthetic rate in the sheep placenta in vivo: the influence of insulin. Placenta 3: 159–164
Zick Y (1989) The insulin receptor: structure and function. CRC Crit Rev Biochem Mol Biol 24: 217–269
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Desoye, G., Hahn, T., Hartmann, M. et al. Insulin receptors in syncytitrophoblast and fetal endothelium of human placenta. Immunohistochemical evidence for developmental changes in distribution pattern. Histochemistry 101, 277–285 (1994). https://doi.org/10.1007/BF00315915
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DOI: https://doi.org/10.1007/BF00315915