2. Nuclear 3D architecture: syncytial knots have distinct
3D organisations in PE
Distinct nuclear aggregate shapes on villi were identified (Figures 1E -
H). The term knots is often used to describe all nuclear aggregates seen
in villi. However, nuclear aggregates can be subdivided in (apoptotic)
knots, bridges and sprouts. Knots, mostly found towards term, are
condensed nuclear aggregates protruding slightly from the villous
surface36. Bridges are aggregated nuclei that connect
two villi and are thought to provide structural support. Sprouts, mainly
common in young placentas, are the initiating points for new developing
villi37. Sprouts (Figure 1F), bridges (Figure 1G), and
knots (Figure1E and 1H, Figure S3) could be easily distinguished from
one another with 3D information. Prominent nuclear accumulations in term
placenta were frequently bridges. Although bridges can be distinguished
on 2D slices (Figure 1A), their interpretation is imaging-depth
dependent and they are easily misinterpreted as knots without additional
3D information (Figure S3).
EO-PE placentas were characterized by presence of wave-like syncytial
knots (WLKs) (Figure 1E). Although WLKs were most dominantly present on
stem villi (Figure 1H), this pattern was also observed on intermediate
villi (Figure 3A lower red arrow), and in villi from hypertensive
pregnancy (Figure S1D). LO-PE placenta had numerous large,
surface-extending knots (Figure 1H). Knots in term control placenta were
frequently small, regional, mildly protruding (Figure 2E). Additionally,
knots in term control placenta were observed in close relation with
so-called vasculosyncytial membranes (Figure S3), which represent major
areas of feto-maternal
exchange38.