Defective pericyte recruitment of villous stromal vessels as the possible etiologic cause of hydropic change in complete hydatidiform mole.

Kyu Rae Kim,Chang Ohk Sung,Tae Jeong Kwon,Jungbok Lee,Stanley J Robboy,Annie Ny Cheung

doi:10.1371/journal.pone.0122266

Kyu Rae Kim, Chang Ohk Sung + Show 4 more

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https://doi.org/10.1371/journal.pone.0122266

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Abstract

The pathogenetic mechanism underlying the hydropic change in complete hydatidiform moles (CHMs) is poorly understood. A growing body of data suggests that pericytes play a role in vascular maturation. Since maturation of villous stromal vessels in CHMs is markedly impaired at early stages, we postulated that a defect in pericytes around stromal vessels in chorionic villi might cause vascular immaturity and subsequent hydropic change. To investigate this, we examined several markers of pericytes, namely, α-smooth muscle actin (α-SMA), platelet-derived growth factor receptor-β (PDGFR-β), and desmin, in 61 normally developing placentas and 41 CHMs with gestational ages of 4–12 weeks. The ultrastructure of villous stromal vessels was also examined. Mature blood vessels from normal placentas show patent vascular lumens and formed hematopoietic components in the villous stroma. α-SMA and PDGFR-β expression in the villous stroma gradually increased and extended from the chorionic plate to peripheral villous branches. The labeled cells formed a reticular network in the villous stroma and, after week 7, encircled villous stromal vessels. In comparison, α-SMA and PDGFR-β expression in the villous stroma and stromal vessels of CHMs was significantly lower (p<0.05). Ultrastructurally, endothelial cells in villous stromal vessels in normal placentas were consistently attached by pericytes after week 7 when the vessels formed distinct lumen, whereas the villous stromal vessels in CHMs consisted of linear chains of endothelial cells, often disclosing primitive clefts without hematopoietic cells inside, and neither pericytes nor basal lamina surrounded the endothelial cells at any gestational age studied. This suggests that pericytes recruitment around villous stromal vessels is defective in CHMs and links to the persistent vascular immaturity of the villous stroma in CHMs, which in turns leads to hydropic villi.

Highlights

Swollen chorionic villi are typically the most prominent histological abnormality in a complete hydatidiform mole (CHM)
We have examined the expression of pericyte immunohistochemical markers, namely, α-smooth muscle actin (αSMA), platelet-derived growth factor receptor-β (PDGFR-β), and desmin, in the villous stroma and villous stromal vessels between normal placentas and CHMs
With increasing gestational age of normal placentas, the intensity of staining for α-smooth muscle actin (α-SMA) and PDGFR-β in villous stroma gradually increased, and their expression gradually extended from the chorionic plate to the peripheral villous stroma (Fig 1 and S1A Table)

Summary

Introduction

Swollen chorionic villi are typically the most prominent histological abnormality in a complete hydatidiform mole (CHM). Due to advances in ultrasonography, moles can be suspected much earlier in pregnancy, often by the 6–8th week, but at this time the vesicles are much smaller [1,2] and difficult to diagnose histologically with certainty. This indicates that hydropic change is a progressive phenomenon that develops over time. Apoptotic cells in the villous stroma are common and exceed CHMs of older gestational ages [3,4,5,6,7] Together, these findings are indicative of deficient vasculogenic differentiation. Over a number of weeks, this leads to the formation of the cisterns grossly visible by late gestation

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