Maternal diabetes influences proliferative potential and cell differentiation in fetoplacental capillaries

Konference: 2013 The 9th Symposium & Workshop on Molecular Pathology and Histo(cyto)chemistry

Kategorie: Nádorová biologie/imunologie/genetika a buněčná terapie

Téma: Invited guests

Číslo abstraktu: 08

Autoři: doc. MUDr. Marie Jirkovská; Martin Jadrníček; Veronika Nedobová; MUDr. Milena Moravcová; As. Vratislav Krejčí; MUDr. Zdeněk Žižka

Structural changes of placenta caused by maternal diabetes mellitus are characterized as delayed villous maturation. It includes among other great variability of vascularity in terminal villi manifested by focal occurrence of either large and strikingly hypovascular villi or large hypervascular villi. Our previous work has shown that in branched terminal villous capillary bed of term placenta, the signs of both the longitudinal and sprouting capillary growth occur till the end of pregnancy, and that the villous capillary bed is more complicated due to enhanced capillary branching in placentas from pregnancies complicated by gestational as well as maternal diabetes type 1. Also the stromal architecture of pathological placental terminal villi shows changed configuration which is favourable for development of altered capillary arrangement, i.e. enhanced capillary branching, more waved capillary course and enlarged capillary diameter. All those morphological changes contribute to the enlargement of the total area of placental capillary wall in order to achieve better oxygen supply.

The rapid development of terminal placental villi and placental capillary bed inside them starts about at 25th week and continues up to the end of gestation. There is no doubt that it is carried out by three well-balanced processes, i.e. cell proliferation, differentiation and apoptosis. Here we tested the hypothesis that the increased angiogenesis in diabetic placenta is connected with greater proliferative potential of cells constituting capillary wall and with greater proportion of differentiating cells in villous capillaries. The Ki-67 antigen as a marker of active phases of cell cycle and nestin as a marker of postmitotic endothelial cells and pericytes were used for the quantitative morphological study of carried on 8 normal and 18 diabetic (DM I) term placentas. In both examined groups, the Ki- 67 positive nuclei occurred in villous cytotrophoblast and cells of capillary wall. In DM I placentas, we observed conspicuously lower frequency of those nuclei in both pathological forms of villi. The mean number of labeled nuclei of cytotrophoblast as well as the mean number of labeled nuclei in the capillary wall per square millimeter of section were significantly lower in DM I group (32.2 ± 14.7 vs. 19.9 ± 12.2 for cytotrophoblast and 10.1 ± 4.6 vs. 5.2 ± 4.5 for cells of capillary wall respectively). The detection of nestin has shown that postmitotic cells are arranged in a patchy manner in the capillary wall. Nestin-positive proportions of the capillary circumference were found also significantly different (0.20 ± 0.05 in control vs. 0.32 ± 0.09 in diabetic placentas).

Our findings suggest that maternal diabetes mellitus influences placental capillary bed in a complex manner. The decreased proliferative potential of cytotrophoblast and cells of capillary wall may cause lower ability of placenta to enlarge the area of syncytiotrophoblast and capillary wall in terminal phase of pregnancy. Moreover, higher proportion of differentiating cells in the capillary wall may be associated with less effective capillary function. These changed qualities of fetoplacental capillary wall attributable to maternal diabetes can adversely influence fetal well-being at the end of pregnancy. This work was supported by the PRVOUK P25/LF1/2.


1. Jirkovska M. et al.: J Vasc Res 2002; 39: 268–278.

2. Jirkovska M. et al.: Placenta 2012; 33: 343–351.

Datum přednesení příspěvku: 26. 4. 2013