Skip to main content
SpringerLink
Log in

Placental toxicity in rats after administration of synthetic glucocorticoids

A morphological, histochemical and immunohistochemical investigation

  • Original Articles
  • Published:
Anatomy and Embryology Aims and scope Submit manuscript

Summary

Administration of the synthetic glucocorticoids dexamethasone and triamcinolone to pregnant rats between gestational day (GD) 16 and 20 caused dose-dependent placental lesions on GD 21 and 22 which were detected by morphological, histochemical and immunohistochemical means. Maternal blood spaces, trophoblast layer and fetal blood vessels were altered primarily in the centre of the placentral labyrinth. Less severe changes were found in the junctional zone, chorionic plate and intraplacental yolk sac. On GD 21, low doses increased the amount of glycogen, while high doses induced a loss of glycogen. γ-glutamyl transpeptidase activity was increased in the spongiotrophoblast and the labyrinthic trophoblast and dipeptidyl peptidase IV activity in fetal capillary endothelium, whereas α-glutamyl aminopeptidase and microsomal alanyl aminopeptidase were not affected. Additionally, in the fetal capillary endothelium an increase of immunoreactivity for the von Willebrand factor occurred. These data suggest that synthetic glucocorticoids affect placental tissues at different and rather specific levels, which may in turn disturb placental function and contribute to fetal maldevelopment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Barash V, Gutman A, Shafrir E (1983) Mechanism of placental glycogen deposition in diabetes in the rat. Diabetologia 24:63–68

    Google Scholar 

  • Blackburn WR, Kaplan HS, McKay DG (1965) Morphologic changes in the developing rat placenta following prednisolone administration. Am J Obstet Gynecol 92:234–246

    Google Scholar 

  • Blanford AT, Murphey BEP (1977) In vitro metabolism of prednisolone, dexamethasone, betamethasone, and cortisol by the human placenta. Am J Obstet Gynecol 127:264–267

    Google Scholar 

  • Brambell FWR, Halliday R (1956) The route by which passive immunity is transmitted from mother to fetus in the rat. Proc Roy Soc Lond Ser B 145:179–185

    Google Scholar 

  • Bridgman J (1948) A morphological study of the development of the placenta of the rat. II. A histological and cytological study of the development of the chorioallantoic placenta of the white rat. J Morphol 83:195–224

    Google Scholar 

  • Bulleit RF, Zimmerman EF (1984) The effects of dexamethasone on palate mesenchymal cell phospholipase activity. Toxicol Appl Pharmacol 75:246–257

    Google Scholar 

  • Cirkel U, Burkart W, Staehler E, Buchholz R (1986) Effects of alloxan-induced diabetes mellitus on the metabolism of the rat placenta. Arch Gynecol 237:155–163

    Google Scholar 

  • Diamant YZ, Neuman S, Shafrir E (1975) Effect of chorionic gonadotropin, triamcinolone, progesterone and estrogen on enzymes of placenta and liver in rats. Biochim Biophys Acta 385:257–267

    Google Scholar 

  • McDonald JK, Barrett AJ (1986) Mammalian proteases: A glossary and bibliography, vol 2, Exopeptidases. Academic Press, London Orlando San Diego New York Austin Montreal Sydney Tokyo Toronto

    Google Scholar 

  • Dostal M, Jelinek R (1971) Induction of cleft palate in rats with intra-amniotic corticoids. Nature 230:464

    Google Scholar 

  • Duval M (1892) La placenta des rongeurs. Ed. Felix Alcan. Paris: Ancienne Librairie Germer Bailliere et Cie

    Google Scholar 

  • Franke M (1969) Feinstruktur der Placenta. Elektronenmikroskopische Untersuchungen über die reifende und reife Placenta der Ratte. VEB Fischer, Jena

    Google Scholar 

  • Gabbe SG, Demers LM, Greep RO, Villee CA (1972) Placental glycogen metabolism in diabetes mellitus. Diabetes 21:1185–1191

    Google Scholar 

  • Garvey D, Scott J (1981) Placental and fetal contraindications of dexamethasone administration to pregnant rats. Experientia 37:757–759

    Google Scholar 

  • Glenn EM, Stafford RO, Lyster SC, Bowman BJ (1957) Relation between biological activity of hydrocortisone analogues and their rates of inactivation by rat liver enzyme systems. Endocrinology 61:128–142

    Google Scholar 

  • Gossrau R (1981) Investigation of proteinases in the digestive tract using r-methoxy-2-naphthylamine (MNA) substrates. J Histochem Cytochem 29:464–480

    Google Scholar 

  • Gossrau R, Graf R (1986) Protease cytochemistry in the murine rodent, guinea-pig and marmoset placenta. Histochemistry 84:530–537

    Google Scholar 

  • Gossrau R, Graf R, Ruhnke M, Hanski C (1987) Proteases in the human full-term placenta. Histochemistry 86:405–413

    Google Scholar 

  • Graf R, Gossrau R (1986) Enzyme histochemistry of the yolk sac diverticula in the mature rodent placenta. Placenta 7:491

    Google Scholar 

  • Graf R, Gossrau R, Frank H-G (1988, in press) Enhancement of immunoreactivity of von Willebrand factor in vascular endothelial cells of rat organs after glucocorticoid administration. Acta Histochem [Suppl]

  • Gunberg DL (1957) Some effects of exogenous hydrocortisone on pregnancy in the rat. Anat Rec 129:133–153

    Google Scholar 

  • Gupta C, Goldman AS (1985) Dexamethasone-induced phospholipase A2-inhibitory proteins (PLIP) influenced by the H-2 histocompatibility region. Proc Soc Exp Biol Med 178:29–35

    Google Scholar 

  • Gupta C, Katsumata M, Goldman AS, Herold R, Piddington R (1984) Glucocorticoid-induced phospholipase A2-inhibitory proteins mediate glucocorticoid teratogenicity in vitro. Proc Natl Acad Sci 81:1140–1143

    Google Scholar 

  • Heller C, Coirini H, DeNicola AF (1981) Binding of 3Hdexamethasone by rat placenta. Endocrinology 5:1697–1702

    Google Scholar 

  • Heller CL, Orti E, DeNicola AF (1986) Regulatory factors of glucocorticoid binding in early and term rat placenta. J Steroid Biochem 25:53–58

    Google Scholar 

  • Heymann E, Mentlein R (1984) Beeinflußt Dipeptidylpeptidase IV Blutdruck und Gerinnung? Klin Wschr 62:2–10

    Google Scholar 

  • Hoet PL (1953) Pregnancy and diabetes. Ciba Foundation Colloq. Endocrinol. 6:330–334

    Google Scholar 

  • Holmes RP, Davies DV (1948) The vascular pattern of the placenta and its development in the rat. J Obstet Gynecol Brit Emp 55:583–607

    Google Scholar 

  • Jaffe EA, Hoyer LW, Nachman RL (1973) Synthesis of antihaemophilic factor antigen by cultured human endothelial cells. J Clin Invest 52:2757–2764

    Google Scholar 

  • Johnson JWC, Beck JC, Haberkern CM (1984) Glucocorticoids and the respiratory distress syndrome. Obstet Gynecol Ann 13:99–129

    Google Scholar 

  • Jones C, Fox H (1976) An ultrastructural and ultrahistochemical study of the placenta of the diabetic woman. J Pathol 119:91–99

    Google Scholar 

  • Kalimi M (1984) Glucocorticoid receptors: From development to aging. A review. Mech Age Dev 24:129–138

    Google Scholar 

  • Kenny AJ (1977) Proteinases associated with cell membranes. In: Barrett AJ (ed) Proteinases in mammalian cells and tissues. North-Holland Publ, Amsterdam

    Google Scholar 

  • Lojda Z, Gossrau R, Schiebler TH (1979) Enzyme histochemistry. A laboratory manual. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Meister A, Tate SS (1976) Glutathione and related γ-glutamyl compounds. Biosynthesis and utilization. Ann Rev Biochem 45:559–604

    Google Scholar 

  • Metz J, Heinrich D, Forssmann WG (1976) Ultrastructure of the labyrinth in the rat full-term placenta. Anat Embryol 149:123–148

    Google Scholar 

  • Murphy BEP, Clark SJ, Donald IR, Pinsky M, Vedady D (1974) Conversion of maternal cortisol to cortisone during placental transfer to the human fetus. Am J Obstet Gynecol 118:538–541

    Google Scholar 

  • Ne'eman Z, Barash V, Rosenmann E, Shafrir E (1987) Localization of glycogen in the placenta of diabetic rats. A light and electron microscopic study. Placenta 8:201–208

    Google Scholar 

  • Orlowski M, Meister A (1970) The γ-glutamyl cycle: A possible transport system for amino acids. Proc Natl Acad Sci USA 67:1248–1255

    Google Scholar 

  • Padykula H (1958) A histochemical and quantitative study of enzymes in the rat's placenta. J Anat (Lond) 92:118–129

    Google Scholar 

  • Padykula HA, Richardson D (1963) A correlated histochemical and biochemical study of glycogen storage in the rat placenta. Am J Anat 112:215–241

    Google Scholar 

  • Pappas PW (1971) The use of a chrome-alum gelatin (subbing) solution as a general adhesive for paraffin sections. Stain Technol 46:121–124

    Google Scholar 

  • Philippens KMH (1976) The manipulation of circadian rhythmus. Arch Toxicol 36:277–303

    Google Scholar 

  • Rooney SA (1985) The surfactant system and lung phospholipid biochemistry. Am Rev Respir Dis 131:439–460

    Google Scholar 

  • Rowland JM, Hendrickx AG (1983) Comparative teratogenicity of triamcinolone acetonide, triamcinolone, and cortisol in the rat. Teratogenesis, Carcinogenesis and Mutagenesis 3:313–320

    Google Scholar 

  • Rowland JM, Althaus ZR, Slikker W (Jr), Hendrickx AG (1983a) Comparative distribution and metabolism of triamcinolone acetonide and cortisol in the rat embryo maternal unit. Teratology 27:333–341

    Google Scholar 

  • Rowland JM, Althaus ZR, Slikker W, Hendrickx AG (1983b) Distribution and metabolism of triamcinolone acetonide in the rat embryomaternal unit during a teratogenically sensitive period. Toxicol Appl Pharmacol 67:70–77

    Google Scholar 

  • Ruggeri ZM, Zimmerman TS (1987) Von Willebrand factor and von Willebrand disease. Blood 70:895–904

    Google Scholar 

  • Schiebler Th, Knoop A (1959) Histochemische und elektronenmikroskopische Untersuchungen an der Rattenplacenta. Z Zellforsch 50:494–552

    Google Scholar 

  • Skrabanek P, Balfe A, McDonald D, McKaigney J, Powell D (1980) Substance P in human cord blood and its degradation by placenta in vitro. Eur J Obstet Gynecol Reprod Biol 11:157–161

    Google Scholar 

  • Sorokin S, Padykula HA (1960) Differentiation of visceral yolk sac in vitro. Anat Rec 136:348

    Google Scholar 

  • Sporn LA, Clavin SI, Marder VJ, Wagner DD (1985) Biosynthesis of von Willebrand protein by human megakaryocytes. J Clin Invest 76:1102–1106

    Google Scholar 

  • Sugimoto M, Kojima A, Endo H (1976) Role of glucocorticoids in terminal differentiation and tissue-specific function. Dev Growth Diff 18:319–327

    Google Scholar 

  • Tye CM, Burton AF (1980) Glycogen deposition in fetal mouse tissues and the effects of dexamethasone. Biol Neonate 38:265–269

    Google Scholar 

  • Vina J, Hernandez R, Puertez R, Palacin M (1986) Inhibition of placental γ-glutamyl transferase results in a decreased placental transfer of alanine. Biochemical Society Transaction 16:614th Meeting, Oxford, pp 306–307

    Google Scholar 

  • Warrell DM, Taylor R (1968) Outcome for the fetus of mothers receiving prednisolone during pregnancy. Lancet i:117–118

    Google Scholar 

  • Wise RJ, Pittman DD, Handin RI, Kaufman RJ, Orkin SH (1988) The propeptide of von Willebrand factor independently mediates the assembly of von Willebrand multimers. Cell 52:229–236

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anatomy, Free University of Berlin, Königin-Luise-Strasse 15, D-1000, Berlin, Federal Republic of Germany

    R. Graf, R. Gossrau & H. G. Frank

Authors
  1. R. Graf
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Gossrau
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. G. Frank
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported by the German Research Foundation (Sfb 174)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Graf, R., Gossrau, R. & Frank, H.G. Placental toxicity in rats after administration of synthetic glucocorticoids. Anat Embryol 180, 121–130 (1989). https://doi.org/10.1007/BF00309763

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00309763

Key words

Search

Navigation