Syncytial nuclei accumulate at the villous surface in IUGR while proliferation is unchanged

Abstract

The data of the present study indicate a previously unknown type of regulation of syncytial stability and function, independent of proliferation. We hypothesize that in IUGR, post-proliferative trophoblast nuclei accumulate at the villous surface of peripheral villous branches. This could possibly reflect the presence of an unknown mechanism controlling syncytial function and stability by modulation of syncytial passage time rather than by modulation of proliferative supply.

Reduced Uteroplacental Perfusion Pressure (RUPP) causes altered trophoblast differentiation and pericyte reduction in the mouse placenta labyrinth

“…Proliferation in term human PE and IUGR placentas is well investigated, and it has been suggested that there is no change in trophoblast proliferation 70 , 71 , when evaluated at term. This supports our observations that in response to RUPP, we see no significant change at E18.5 in proliferation.…”

The Density of Cell Nuclei at the Materno-Fetal Exchange Barrier is Sexually Dimorphic in Normal Placentas, but not in IUGR

“…non-proliferative) cell nuclei of villous trophoblast were subject to this effect, the unique bi-layered architecture of villous trophoblast as an epithelium comes into focus. It is clear that most of the PCNA-negative cell nuclei are part of the apical trophoblast layer, the syncytiotrophoblast 35,37 . Syncytiotrophoblast is the central tissue organizing materno-fetal transport and traffic 30 and the present study shows that this is the sexually dimorphic part of villous trophoblast.…”

“…The loss of topologic orientation in 3D which is associated with 2D histology is especially relevant for tree structures which can only be fully interpreted in 3D. This shortcoming was overcome by the introduction of next-generation quantitative 3D histology of the human placenta, which guarantees instantaneous orientation in 3D and connects any identifiable structure like trophoblast cell nuclei to their 3D site of occurrence in the villous tree 35,36 .…”

“…In the present study we used this novel 3D microscopic approach 35,36 to analyze villous trees of clinically normal pregnancies (normal) and placentas of pregnancies with intrauterine growth retardation (IUGR) at a challenging but manageable workload. We focused our study on all nuclei of villous trophoblast (i. e. cyto- and syncytiotrophoblast) occurring in terminal (bT0) and preterminal (bT1) peripheral branches 35,36 , which are a technically feasible target for 3D microscopy. Since differentiation of cyto- and syncytiotrophoblastic nuclei is a genuine 2D-microscopic feature, we used the proliferation marker PCNA as an observer-independent proxy to this.…”

“…Since differentiation of cyto- and syncytiotrophoblastic nuclei is a genuine 2D-microscopic feature, we used the proliferation marker PCNA as an observer-independent proxy to this. Most of the PCNA-positive nuclei will be cytotrophoblast nuclei, while most of the PCNA-negative nuclei will be syncytial 35 . For the first time we show, that the density of PCNA-negative (i.e.…”