Trophoblast and knots
Hypoxia (and associated trophoblast damage) is central in current
pathophysiological hypotheses of PE42. In PE,
trophoblast turnover is no longer balanced. Apoptosis is
increased43, differentiation and fusion of the
so-called cytotrophoblast to form the syncytium is
decreased44, while cytotrophoblast proliferation is
reported to be increased or unaltered45-47. Altered
trophoblast function provides a potential clarification of observed
structural abnormalities in PE (Figure1C and 1D).
Moreover, placental hypoxia has been found to promote the aggregation of
syncytial knots 48. Increased syncytial knotting is a
clear hallmark of pre-eclamptic placentas13, 35.
Distinct 3D conformations (Figures 1E-1H) of knots are potentially
related to different pathological mechanisms (i.e., being apoptotic or a
mechanism to sequester effete nuclei and create regions for diffusional
exchange). Especially WLKs were dominantly present on the investigated
EO-PE placenta (Figure 1E). Nonetheless, wave-like apoptotic shedding is
not specific for PE and has been described in stem villi from cases with
severe IUGR, without PE35, 49. Quantification of knots
(shape/volume) could potentially aid in subdivision of pathological,
apoptotic, or non-pathological (including sprouts and bridges) knots
accordingly. To our knowledge, different shapes of knots have been
described50, but quantitative data regarding relative
incidences of alternative knot shapes is lacking. Current developed
methodology provides an approach to quantitatively investigate knots and
their shapes.