Skip to main content
PMC home page
Journal of Anatomy logoLink to Journal of Anatomy
. 2000 Aug;197(Pt 2):263–274. doi: 10.1046/j.1469-7580.2000.19720263.x

Stereological comparison of 3D spatial relationships involving villi and intervillous pores in human placentas from control and diabetic pregnancies

TERRY M MAYHEW 1,✉, INDIRA C JAIRAM 1
PMCID: PMC1468125  PMID: 11005718

Abstract

In human placenta, 3D spatial relationships between villi and the maternal vascular bed determine intervillous porosity and this, in turn, influences haemodynamics and transport. Recently-developed stereological methods were applied in order to examine and quantify these relationships. Placentas were collected after 37 wk from control pregnancies and those associated with maternal diabetes mellitus classified according to duration and severity (White classification scheme). Two principal questions were addressed: (1) are normal spatial arrangements maintained in well-controlled diabetes mellitus? and (2) do arrangements vary between diabetic groups? To answer these questions, tissue sections cut at random positions and orientations were generated by systematic sampling procedures. Volume densities of villi (terminal+intermediate), intervillous spaces and perivillous fibrin-type fibrinoid deposits were estimated by test point counting and converted to global volumes after multiplying by placental volumes. Design-based estimates of the sizes (volume- and surface-weighted volumes) of intervillous ‘pores’ were obtained by measuring the lengths of point- and intersection-sampled intercepts. From these, theoretical numbers of pores were calculated. Model-based estimates (cylinder model) of the hydraulic diameters and lengths of pores were also made. Second-order stereology was used to examine spatial relationships within and between villi and pores and to test whether pair correlation functions deviated from the value expected for ‘random’ arrangements. Estimated quantities did not differ significantly between diabetic groups but did display some departures from control values in non-insulin-dependent (type 2) diabetic placentas. These findings support earlier studies which indicate that essentially normal microscopical morphology is preserved in placentas from diabetic subjects with good glycaemic control. Therefore, it is likely that fetal hypoxia associated with maternal diabetes mellitus is due to metabolic disturbances rather than abnormalities in the quantities or arrangements of maternal vascular spaces.

Keywords: Diabetes mellitus, pregnancy, placenta

Full Text

The Full Text of this article is available as a PDF (315.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aherne W., Dunnill M. S. Quantitative aspects of placental structure. J Pathol Bacteriol. 1966 Jan;91(1):123–139. doi: 10.1002/path.1700910117. [DOI] [PubMed] [Google Scholar]
  2. Alsat E., Wyplosz P., Malassiné A., Guibourdenche J., Porquet D., Nessmann C., Evain-Brion D. Hypoxia impairs cell fusion and differentiation process in human cytotrophoblast, in vitro. J Cell Physiol. 1996 Aug;168(2):346–353. doi: 10.1002/(SICI)1097-4652(199608)168:2<346::AID-JCP13>3.0.CO;2-1. [DOI] [PubMed] [Google Scholar]
  3. Björk O., Persson B. Placental changes in relation to the degree of metabolic control in diabetes mellitus. Placenta. 1982 Oct-Dec;3(4):367–378. doi: 10.1016/s0143-4004(82)80030-1. [DOI] [PubMed] [Google Scholar]
  4. Björk O., Persson B. Villous structure in different parts of the cotyledon in placentas of insulin-dependent diabetic women. A morphometric study. Acta Obstet Gynecol Scand. 1984;63(1):37–43. doi: 10.3109/00016348409156271. [DOI] [PubMed] [Google Scholar]
  5. Boyd P. A., Scott A., Keeling J. W. Quantitative structural studies on placentas from pregnancies complicated by diabetes mellitus. Br J Obstet Gynaecol. 1986 Jan;93(1):31–35. doi: 10.1111/j.1471-0528.1986.tb07809.x. [DOI] [PubMed] [Google Scholar]
  6. Burton G. J., Palmer M. E. Eradicating fetomaternal fluid shift during perfusion fixation of the human placenta. Placenta. 1988 May-Jun;9(3):327–332. doi: 10.1016/0143-4004(88)90040-9. [DOI] [PubMed] [Google Scholar]
  7. Casson I. F., Clarke C. A., Howard C. V., McKendrick O., Pennycook S., Pharoah P. O., Platt M. J., Stanisstreet M., van Velszen D., Walkinshaw S. Outcomes of pregnancy in insulin dependent diabetic women: results of a five year population cohort study. BMJ. 1997 Aug 2;315(7103):275–278. doi: 10.1136/bmj.315.7103.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Frank H. G., Malekzadeh F., Kertschanska S., Crescimanno C., Castellucci M., Lang I., Desoye G., Kaufmann P. Immunohistochemistry of two different types of placental fibrinoid. Acta Anat (Basel) 1994;150(1):55–68. doi: 10.1159/000147602. [DOI] [PubMed] [Google Scholar]
  9. Gundersen H. J., Jensen E. B. Stereological estimation of the volume-weighted mean volume of arbitrary particles observed on random sections. J Microsc. 1985 May;138(Pt 2):127–142. doi: 10.1111/j.1365-2818.1985.tb02607.x. [DOI] [PubMed] [Google Scholar]
  10. Gundersen H. J., Jensen E. B. The efficiency of systematic sampling in stereology and its prediction. J Microsc. 1987 Sep;147(Pt 3):229–263. doi: 10.1111/j.1365-2818.1987.tb02837.x. [DOI] [PubMed] [Google Scholar]
  11. Haust M. D. Maternal diabetes mellitus--effects on the fetus and placenta. Monogr Pathol. 1981;(22):201–285. [PubMed] [Google Scholar]
  12. Huppertz B., Frank H. G., Kingdom J. C., Reister F., Kaufmann P. Villous cytotrophoblast regulation of the syncytial apoptotic cascade in the human placenta. Histochem Cell Biol. 1998 Nov;110(5):495–508. doi: 10.1007/s004180050311. [DOI] [PubMed] [Google Scholar]
  13. Jones C. J., Fox H. Placental changes in gestational diabetes. An ultrastructural study. Obstet Gynecol. 1976 Sep;48(3):274–280. [PubMed] [Google Scholar]
  14. Karimu A. L., Burton G. J. Star volume estimates of the intervillous clefts in the human placenta: how changes in umbilical arterial pressure might influence the maternal placental circulation. J Dev Physiol. 1993 Mar;19(3):137–142. [PubMed] [Google Scholar]
  15. Klebe J. G., Ingomar C. J. Placental transfusion in infants of diabetic mothers elucidated by placental residual blood volume. Acta Paediatr Scand. 1974 Jan;63(1):59–64. doi: 10.1111/j.1651-2227.1974.tb04349.x. [DOI] [PubMed] [Google Scholar]
  16. Lang I., Hartmann M., Blaschitz A., Dohr G., Kaufmann P., Frank H. G., Hahn T., Skofitsch G., Desoye G. Differential lectin binding to the fibrinoid of human full-term placenta: correlation with a fibrin antibody and the PAF-Halmi method. Acta Anat (Basel) 1994;150(3):170–177. doi: 10.1159/000147615. [DOI] [PubMed] [Google Scholar]
  17. Lee R., Mayhew T. M. Star volumes of villi and intervillous pores in placentae from low and high altitude pregnancies. J Anat. 1995 Apr;186(Pt 2):349–355. [PMC free article] [PubMed] [Google Scholar]
  18. Mattfeldt T., Frey H., Rose C. Second-order stereology of benign and malignant alterations of the human mammary gland. J Microsc. 1993 Aug;171(Pt 2):143–151. doi: 10.1111/j.1365-2818.1993.tb03368.x. [DOI] [PubMed] [Google Scholar]
  19. Mayhew T. M., Burton G. J. Methodological problems in placental morphometry: apologia for the use of stereology based on sound sampling practice. Placenta. 1988 Nov-Dec;9(6):565–581. doi: 10.1016/0143-4004(88)90001-x. [DOI] [PubMed] [Google Scholar]
  20. Mayhew T. M., Leach L., McGee R., Ismail W. W., Myklebust R., Lammiman M. J. Proliferation, differentiation and apoptosis in villous trophoblast at 13-41 weeks of gestation (including observations on annulate lamellae and nuclear pore complexes). Placenta. 1999 Jul-Aug;20(5-6):407–422. doi: 10.1053/plac.1999.0399. [DOI] [PubMed] [Google Scholar]
  21. Mayhew T. M. Patterns of villous and intervillous space growth in human placentas from normal and abnormal pregnancies. Eur J Obstet Gynecol Reprod Biol. 1996 Sep;68(1-2):75–82. doi: 10.1016/0301-2115(96)02486-4. [DOI] [PubMed] [Google Scholar]
  22. Mayhew T. M. Quantitative description of the spatial arrangement of organelles in a polarised secretory epithelial cell: the salivary gland acinar cell. J Anat. 1999 Feb;194(Pt 2):279–285. doi: 10.1046/j.1469-7580.1999.19420279.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mayhew T. M., Simpson R. A. Quantitative evidence for the spatial dispersal of trophoblast nuclei in human placental villi during gestation. Placenta. 1994 Dec;15(8):837–844. doi: 10.1016/s0143-4004(05)80185-7. [DOI] [PubMed] [Google Scholar]
  24. Mayhew T. M., Sisley I. Quantitative studies on the villi, trophoblast and intervillous pores of placentae from women with well-controlled diabetes mellitus. Placenta. 1998 Jul-Aug;19(5-6):371–377. doi: 10.1016/s0143-4004(98)90076-5. [DOI] [PubMed] [Google Scholar]
  25. Mayhew T. M., Sørensen F. B., Klebe J. G., Jackson M. R. Growth and maturation of villi in placentae from well-controlled diabetic women. Placenta. 1994 Jan;15(1):57–65. doi: 10.1016/s0143-4004(05)80236-x. [DOI] [PubMed] [Google Scholar]
  26. Mayhew T. M., Sørensen F. B., Klebe J. G., Jackson M. R. Oxygen diffusive conductance in placentae from control and diabetic women. Diabetologia. 1993 Oct;36(10):955–960. doi: 10.1007/BF02374479. [DOI] [PubMed] [Google Scholar]
  27. Mayhew T. M. The new stereological methods for interpreting functional morphology from slices of cells and organs. Exp Physiol. 1991 Sep;76(5):639–665. doi: 10.1113/expphysiol.1991.sp003533. [DOI] [PubMed] [Google Scholar]
  28. Mayhew T. M., Wadrop E. Placental morphogenesis and the star volumes of villous trees and intervillous pores. Placenta. 1994 Feb-Mar;15(2):209–217. doi: 10.1016/s0143-4004(05)80457-6. [DOI] [PubMed] [Google Scholar]
  29. Nelson D. M. Apoptotic changes occur in syncytiotrophoblast of human placental villi where fibrin type fibrinoid is deposited at discontinuities in the villous trophoblast. Placenta. 1996 Sep;17(7):387–391. doi: 10.1016/s0143-4004(96)90019-3. [DOI] [PubMed] [Google Scholar]
  30. Nylund L., Lunell N. O., Lewander R., Persson B., Sarby B. Uteroplacental blood flow in diabetic pregnancy: measurements with indium 113m and a computer-linked gamma camera. Am J Obstet Gynecol. 1982 Oct 1;144(3):298–302. doi: 10.1016/0002-9378(82)90582-8. [DOI] [PubMed] [Google Scholar]
  31. Reed M. G., Howard C. V. Stereological estimation of covariance using linear dipole probes. J Microsc. 1999 Aug;195(Pt 2):96–103. doi: 10.1046/j.1365-2818.1999.00592.x. [DOI] [PubMed] [Google Scholar]
  32. Reed M. G., Howard C. V. Surface-weighted star volume: concept and estimation. J Microsc. 1998 Jun;190(Pt 3):350–356. doi: 10.1046/j.1365-2818.1998.00331.x. [DOI] [PubMed] [Google Scholar]
  33. Singer D. B., Liu C. T., Widness J. A., Ellis R. A. Placental morphometric studies in diabetic pregnancies. Placenta Suppl. 1981;3:193–202. [PubMed] [Google Scholar]
  34. Stoz F., Schuhmann R. A., Haas B. Morphohistometric investigations in placentas of gestational diabetes. J Perinat Med. 1988;16(3):205–209. doi: 10.1515/jpme.1988.16.3.205. [DOI] [PubMed] [Google Scholar]
  35. Stringer B. M., Wynford-Thomas D., Williams E. D. Physical randomization of tissue architecture: an alternative to systemic sampling. J Microsc. 1982 May;126(Pt 2):179–182. doi: 10.1111/j.1365-2818.1982.tb00369.x. [DOI] [PubMed] [Google Scholar]
  36. Teasdale F. Histomorphometry of the human placenta in Class B diabetes mellitus. Placenta. 1983 Jan-Apr;4(1):1–12. doi: 10.1016/s0143-4004(83)80012-5. [DOI] [PubMed] [Google Scholar]
  37. Teasdale F. Histomorphometry of the human placenta in Class C diabetes mellitus. Placenta. 1985 Jan-Feb;6(1):69–81. doi: 10.1016/s0143-4004(85)80034-5. [DOI] [PubMed] [Google Scholar]
  38. Teasdale F. Histomorphometry of the placenta of the diabetic women: class A diabetes mellitus. Placenta. 1981 Jul-Sep;2(3):241–251. doi: 10.1016/s0143-4004(81)80007-0. [DOI] [PubMed] [Google Scholar]
  39. Teasdale F., Jean-Jacques G. Morphometry of the microvillous membrane of the human placenta in maternal diabetes mellitus. Placenta. 1986 Jan-Feb;7(1):81–88. doi: 10.1016/s0143-4004(86)80020-0. [DOI] [PubMed] [Google Scholar]
  40. WHITE P. Pregnancy complicating diabetes. Am J Med. 1949 Nov;7(5):609–616. doi: 10.1016/0002-9343(49)90382-4. [DOI] [PubMed] [Google Scholar]
  41. Widness J. A., Susa J. B., Garcia J. F., Singer D. B., Sehgal P., Oh W., Schwartz R., Schwartz H. C. Increased erythropoiesis and elevated erythropoietin in infants born to diabetic mothers and in hyperinsulinemic rhesus fetuses. J Clin Invest. 1981 Mar;67(3):637–642. doi: 10.1172/JCI110078. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Widness J. A., Teramo K. A., Clemons G. K., Voutilainen P., Stenman U. H., McKinlay S. M., Schwartz R. Direct relationship of antepartum glucose control and fetal erythropoietin in human type 1 (insulin-dependent) diabetic pregnancy. Diabetologia. 1990 Jun;33(6):378–383. doi: 10.1007/BF00404643. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Anatomy are provided here courtesy of Anatomical Society of Great Britain and Ireland

RESOURCES