Pericyte coverage of fetoplacental vessels in pregnancies complicated by DMI

Introduction: Diabetes mellitus type I (DMI) in pregnant women is a risk factor for impairing the physiological intrauterine development of the fetus. Consistent with the morphological abnormalities found in the placentas of women with DMI, the capillary bed in the terminal villae is more branched in the placentas from pregnancies with gestational diabetes mellitus. Angiogenesis occures in the placenta until delivery, as demonstrated by expression of markers for neovasculature in the placenta at term. Perivascular cells such as smooth muscle cells and pericytes participate in the vascular wall formation in neovessels. According to some authors, neovessels are covered by perivascular cells to a lesser extent than mature vessels and, in the placentas, this situation occurs in pregnancies in high altitudes. This might reflect more active angiogenesis or an adaptation of the microvascular wall morphology to lower oxygen.

Aim: Here we studied the extent of pericyte coverage in microvessels of normal pregnancies and pregnancies complicated by DMI. In addition we characterized the phenotype of pericytes in normal and DMI pregnancies.

Material and Methods: The placentas from normal pregnancies (n=8) and placentas from mothers with DMI (n=18) were obtained at the time of delivery. The specimens were collected using unbiased systematic random sampling. They were fixed with formaldehyde and embedded in paraffin. Immunohistochemical detection was performed using standard procedures. Images for quantification were collected using Leica SPE CLSM and analyzed in Image J.

Results: Pericytes of capillaries in terminal and intermediate villi were immunoreactive for smooth muscle actin (SMA), but they were negative for intermediate filament desmin. We thus decided to use SMA as a marker for quantitation of pericyte coverage in placental microvessels. The extent of pericyte coverage was quite variable. However SMA+ pericytes regularly avoided segments of capillary wall forming vasculosyncytial membranes. The proportion of capillaries covered with SMA+ pericytes (microvessel pericyte coverage index) was 84+13% in normal vs. 79,5+13% in DMI pregnancies. The extent of pericyte coverage around the vessel circumference was 38±11% in normal vs. 33+10% in DMI pregnancies. Diabetic women were also grouped according to their compensation reflected by levels of glycated hemoglobin (GlyHb). Extent of pericyte coverage around the vessel circumference was 35±7% in the group with normal GlyHb vs. 32+12% in the group with elevated GlyHb.

Conclusion: Immunohistochemical phenotyping of perivascular cells in human fetoplacental vessels showed that pericytes surrounding capillaries in terminal and intermediate villi are SMA+/desmin- perivascular cells. There is further great variability of these cells in different organs. The phenotype of pericytes in normal pregnancies and in pregnancies complicated with DMI was virtually identical. No statistically significant difference in the extent of pericyte coverage around the vessel circumference between DMI and normal pregnancies was found. The morphology of angiogenic fetoplacental vessels in DMI is thus different from the placental microvasculature developing under low oxygen pressures such as in high altitudes.

The work was supported by the Research Project MSM 0021620807 and Grant GACR 304/09/0733.