title: Syncytial nuclear aggregates in normal placenta show increased nuclear condensation, but apoptosis and cytoskeletal redistribution are uncommon.
abstract: BACKGROUND
  Syncytial nuclear aggregates (SNAs) are increased in pregnancy complications; however, little is known about their origin or function. This study aimed to characterise SNAs in more detail than has been reported previously.
  
  
  METHODS
  Immunohistochemistry and morphological examination at the light and ultrastructural level were used to determine the nature and structure of SNAs.
  
  
  RESULTS
  SNAs comprising bridges and syncytial knots had similar frequency with 974 per mm3 of villous tissue (IQR 717-1193) and 833 per mm3 (IQR 766-1190), respectively while there were approximately four times as many sectioning artefacts than knots and bridges combined. SNAs had increased proportions of condensed nuclei compared to the remaining syncytiotrophoblast (33.3% vs. 8.9%) and decreased proportions of euchromatic nuclei (0.0% vs. 16.2%), as assessed by examination of an electron micrograph archive. SNAs showed little evidence of apoptosis, with weak positivity for the apoptosis markers M30-neoepitope at 16.6% and TUNEL at 10.0%; strong staining was rarely seen for either marker. Immunofluorescence demonstrated rare association of actin (α, β or γ) with SNAs, whereas tubulin was in close proximity to SNAs and cytokeratin was seen within and surrounding SNAs.
  
  
  CONCLUSIONS
  M30-positive SNAs traced through serial sections were significantly more likely to be syncytial knots or sectioning artefacts than bridges. Nuclei within SNAs showed signs consistent with degeneration; however, this is unlikely to be an apoptotic process. There are few changes in configuration of cytoskeletal proteins around SNAs.
  
  
  CONCLUSIONS
  These data suggest that the biogenesis and functional significance of SNAs still require resolution.
authors.affiliation: Institute of Human Development, University of Manchester, Maternal and Fetal Health Research Centre, UK. sarah.coleman@postgrad.manchester.ac.uk
authors.forename: S J
authors.initials: SJ
authors.lastname: Coleman
authors.forename: L
authors.initials: L
authors.lastname: Gerza
authors.forename: C J P
authors.initials: CJ
authors.lastname: Jones
authors.forename: C P
authors.initials: CP
authors.lastname: Sibley
authors.forename: J D
authors.initials: JD
authors.lastname: Aplin
authors.forename: A E P
authors.initials: AE
authors.lastname: Heazell
mesh_terms: D000199:Actins / Q000032:analysis; D017209:Apoptosis; D002467:Cell Nucleus / Q000648:ultrastructure*; D003599:Cytoskeleton / Q000737:chemistry / Q000648:ultrastructure*; D005260:Female; D005455:Fluorescent Antibody Technique; D015726:Giant Cells / Q000648:ultrastructure*; D006801:Humans; D020287:In Situ Nick-End Labeling; D007633:Keratins / Q000032:analysis; D008854:Microscopy, Electron; D010920:Placenta / Q000648:ultrastructure*; D011247:Pregnancy; D014404:Tubulin / Q000032:analysis
chemical_list: D000199:Actins; D014404:Tubulin; D007633:Keratins