Histomorphometric study of placental villi vascular volume in toxemia and diabetes

Summary

The quantitative changes in the vascular tree in placentas from pregnancies complicated by diabetes mellitus and preeclampsia (PE) are not well defined. The purpose of this study was to quantify placental villi cross-sectional area of capillaries assessed by a computerized morphometry system in pregnancies complicated by PE (n = 23), well-controlled pregestational diabetes mellitus (PGDM; n = 10), and healthy controls (n = 13). Our aims were to test whether villous capillarization volume was changed in PE without intrauterine growth restriction or PGDM compared with the control group and to study these effects in 3 different areas of the placenta. Examination of placentas in women with PGDM and PE revealed limited pathological changes on light microscopic examination. However, the morphometric analysis revealed a more than 5-fold decrease of villous vascular volume in PGDM compared with controls (P = .003) and a 1.6-fold decrease in the PE group that did not reach statistical significance. These findings show quantitative changes in the villous vascular tree in PGDM that are not detectable by conventional light microscopy and suggest that morphometric analysis of the capillary tree may have diagnostic importance in this entity. The findings differ significantly from those previously reported in pregestational diabetes and do not differ significantly from those reported in PE without intrauterine growth restriction.

Introduction

The placenta is a unique organ of limited life span, interposed between two separate individuals. The main functional units of the placenta are the chorionic villi; within them, fetal blood is separated from maternal blood in the surrounding intervillous space by vasculosyncytial membranes overlying dilated fetal capillaries [1], [2]. In normal human pregnancy, capillary growth is biphasic, involving an initial phase of branching angiogenesis with formation of tightly looped capillaries, followed by a phase of increased nonbranching angiogenesis with formation of longer capillaries [3], [4], [5]. Vascular patterns and villous shapes vary in pregnancies complicated by fetal hypoxia; there is a shift toward branching angiogenesis in preeclampsia (PE) pregnancies or prevalence of nonbranching angiogenesis in pregestational diabetes mellitus (PGDM) [6], [7], [8], [9].

Placentas from well-controlled diabetic patients are not heavier than those from healthy pregnant women but still show similar morphological abnormalities to those from patients with inadequate glycemic control [10], [11], [12], [13].

Increased fetoplacental angiogenesis in PGDM has been described and may be associated with increased capillary villous length, endothelial proliferation influenced by relationships between pericytes and endothelial cells [6], [8], [9], [14], [15], [16], [17]. Proliferation of endothelial cells, significant thickening of basal membranes of trophoblast, separation of basal membranes in basal capillaries, distension and disarrangements of perivascular space, and decrease of vascular surface of terminal villi are significant factors contributing to fetal anoxia in pregnancy complicated by diabetes mellitus [14], [18].

In PE, uteroplacental circulation is compromised and villi are exposed to a more focal hypoxia, which induces more heterogeneous maturation with normal or impoverished growth of capillaries [6], [7]. In PE associated with intrauterine growth restriction (IUGR), capillary volumes may be reduced [6], [7], [19], [20], [21], [22]. However, recent studies have suggested that the reduced capillary growth is more likely to be because of IUGR than to PE [6], [7], [19], [23], [24].

There is no absolute correlation between the severity of toxemia and the magnitude of the histological changes [2], [18], [19], [20].

Taken together, this suggests a primary defect in the placental vascular tree in placentas from diabetic and preeclamptic mothers. This would be in line with the many vascular abnormalities that are prevalent in the systemic circulation in diabetic patients. The rapid growth of the placental vascular tree, which is unsurpassed in any other organ in adult life, makes it an ideal target to search for early vascular changes of diabetes. We were therefore interested to study the placental vascular tree from diabetic and preeclamptic mothers using quantitative measurements.

A systematic morphometric analysis of the placental vascular tree is required to better evaluate its functional and structural properties. Changes in the structures of placenta, using morphological criteria of villous arborization, are divisible into different topological regions. These are known as the stem, intermediate (mature and immature), and terminal villi, based on villous caliber and vessel type. Growth of villous volume during gestation is mainly confined to intermediate and terminal villi. All principal tissue compartments (trophoblast, stroma, fetal capillaries) expand during gestation. Within these villi, maturation involves differential growth of the fetal capillary bed and decline in the relative amount of stromal connective tissue [4], [5], [25].

This is of more than academic relevance because there are currently no completely specific histological criteria for toxemia and PGDM. The application of strict morphometric methods may help to assess subtle quantitative changes that are not apparent on regular microscopy. We therefore used a computerized morphometric detection method for analyzing capillary volume in histological cross-sectional area and compared villous capillary volume between normal placentas, placentas from mothers with well-controlled PGDM, and those from PE without IUGR subjects.