Fig 1.
Histological changes and immunohistochemical labeling for pericyte markers in normal placentas showing significantly increased expressions of α-SMA and PDGFR-β along the vascular maturation and lumen formation.
At week 4 of gestation (GW4), chorionic villi do not exhibit signs of vasculogenesis (a). Expression of α-SMA is confined to the chorionic plate (b, arrows), but not expressed in the villous stroma (b, inlet). PDGFR-β (c) and Desmin (d) are not expressed in the villous stroma. During weeks 5–6 of gestation (GW5-6), when the stroma begins to form angiogenic cell cords (e, arrows), expression of α-SMA begins to extend from chorionic plate (CP) to the villous stroma (f, inlet), but expression of α-SMA, PDGFR-β and desmin is not detected in angiogenic cell cords (arrows in f, g, h). After week 7, when the villous stroma forms mature blood vessels with lumens (i), expression of α-SMA (j and n) and PDGFR-β (k and o) markedly increases in the villous stroma forming a reticular network and encircles blood vessels (arrows in j, n, k, and o). Desmin is slightly increased in the villous stroma at week 10 (p), but is not detected in vascular structures during the entire study period (arrows in h, l, and p).
Fig 2.
Histological changes and immunohistochemical labeling for pericyte markers in CHMs at various gestational ages.
The villi have a basophilic stroma and immature vascular structures (a, arrows) that lack a distinct lumen and do not contain hematopoietic components. Note many karyorrhectic debris in vascular structure as well as in the stroma. α-SMA expression is either not expressed (b) or is weakly (c) to moderately expressed in the villous stroma, regardless of gestational age, but not in immature vascular structures (c, arrows). In one sample, α-SMA was aberrantly detected in vascular structures (d, arrows), but not detected in the surrounding villous stroma. PDGFR-β is diffusely and strongly expressed in the villous stroma in all samples, regardless of gestational age (e), but vascular expression of PDGFR-β was rarely seen (e, arrows). Desmin shows variable levels of expression in the villous stroma, but is not detected in vascular structures (f, arrows).
Fig 3.
Graphical analysis of the expression levels of pericyte markers in normal placentas and CHMs.
α -SMA expression in the villous stroma (a) and stromal vessels (b) is consistently lower in CHMs than in normal placentas, regardless of gestational age. (c-d), PDGFR expression in the villous stroma (c) and around stromal vessels (d) increases linearly with gestational age in normal placentas, whereas its expression does not change with gestational age in CHM, although the difference is not statistically significant. (e-f), Desmin expression in the villous stroma of normal placentas increases linearly with gestational age up to 8 weeks, whereas it does not markedly change in CHMs (e). Desmin expression is not detected in stromal vessels of normal placentas or CHMs at any gestational age (f). (*p<0.05; **p<0.01; ***p<0.001).
Fig 4.
Conventional transmission electron microscopy of stromal vessels in chorionic villi of normal placentas (a-d) and CHMs (e-f) between weeks 6 and 11 of gestation.
In chorionic villi of normal placentas at week 6 of gestation, immature angiogenic cell cords only contain endothelial cells, not pericytes (a). Neither a distinct vascular lumen nor a basal lamina around endothelial cells has formed. At week 7 (b), a well developed stromal vessel is lined with endothelial cells that are attached by pericytes. This vessel has a distinct lumen that contains immature hematopoietic components (b). At week 11 (c-d), mature stromal vessel contain mature or nucleated red blood cells and are lined with endothelial cells and mature pericytes. The endothelial cells and pericytes share a basal lamina. By contrast, CHMs contain immature vascular structures at week 8 (e) and week 11 (f) that are composed of degenerating endothelial cells without pericytes. Neither basal lamina nor distinct pericytes have developed. (E, endothelial cells; PC, pericyte; A, apoptotic cells).