title: Syncytial knots (Tenney-Parker changes) in the human placenta: evidence of loss of transcriptional activity and oxidative damage.
abstract: Syncytiotrophoblast is the multinucleated epithelium of the placenta. Although many nuclei are dispersed within the syncytioplasm, others are aggregated into specializations referred to as true and false syncytial knots, and syncytial sprouts. Nuclei within true knots display highly condensed chromatin and are thought to be aged and effete. True knots increase in frequency with gestational age. Excessive formation (Tenney-Parker change) is associated with placental pathology, and a knotting index is used to assess severity. However, this index is potentially confounded by the creation of artifactual appearances (false knots) through tangential sectioning. In addition, knots must be distinguished from syncytial sprouts, which are markers of trophoblast proliferation. Here, we distinguish between sprouts, true knots, and false knots using serial sections and perform IHC for proliferating cell nuclear antigen, upstream binding factor, RNA polymerase II, and 8-oxo-deoxyguanosine as markers of recent incorporation, transcriptional activity, and oxidative damage. Villous explants were exposed to hydrogen peroxide to test the relationship between transcriptional activity and oxidative damage. Sprouts and false knots were found to contain recently incorporated and transcriptionally active nuclei. By contrast, most nuclei within true knots are negative for transcriptional markers but positive for 8-oxo-deoxyguanosine. In vitro, we observed a negative correlation between transcriptional activity and oxidative damage. These findings demonstrate that true knots contain effete damaged nuclei and provide IHC markers for their identification.
authors.affiliation: Centre for Trophoblast Research and the Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Norah M E
authors.initials: NM
authors.lastname: Fogarty
authors.forename: Anne C
authors.initials: AC
authors.lastname: Ferguson-Smith
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Burton
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D015415:Biomarkers / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018384:Oxidative Stress; D010920:Placenta / Q000378:metabolism / Q000473:pathology; D035463:Pol1 Transcription Initiation Complex Proteins / Q000378:metabolism; D011247:Pregnancy; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D015533:Transcriptional Activation; D014327:Trophoblasts / Q000378:metabolism / Q000473:pathology*
chemical_list: D015415:Biomarkers; D035463:Pol1 Transcription Initiation Complex Proteins; D018809:Proliferating Cell Nuclear Antigen; C063844:transcription factor UBF; D000080242:8-Hydroxy-2'-Deoxyguanosine; D012319:RNA Polymerase II; D003849:Deoxyguanosine