Structural alterations in the placental villous tree in well-controlled gestational diabetes mellitus

INTRODUCTION: A poorly controlled gestational diabetes mellitus (GDM), a metabolic disorder affecting glucose regulation, can lead to macrosomia in both, the placenta and the fetus. A well-managed GDM usually results in an uncomplicated pregnancy. Though some qualitative histopathological changes have been described in such uncomplicated pregnancies, a quantitative description of the structural alterations is still missing. The aim of this study is to assess the villous trophoblast and the villous tree quantitatively in GDM placentas, stratified according to the fetal sex. METHODS: The villous trees from 20 placentas (10 female and 10 male) affected by GDM and 20 Control placentas (10 female and 10 male) were investigated quantitatively by Stereology and 3D microscopy. The measurement of partial volumes of contractile and non-contractile parts of the villous tree was based on immunohistochemical detection of perivascular myofibroblasts. The villous trophoblast was assessed by 3D microscopy to measure the nuclear surface density. RESULTS: Only the female GDM placentas show an increase in the density of proliferative trophoblast nuclei and a decrease in the density of non-proliferative trophoblast nuclei. The branching index is reduced in GDM placentas irrespective of the sex. No significant difference was observed in the volumes of the villous tree, the intervillous space, and the fetal vessels. Similarly, the diffusion distance remained unchanged. CONCLUSION: Even in well-controlled GDM pregnancies, the villous trophoblast shows a sexually dimorphic alteration in the density of proliferative and non-proliferative nuclei. The branching index, however, is reduced for both villous compartments, independent of fetal sex.