Tying the placenta in knots - understanding nuclear aggregates in the syncytiotrophoblast

Abstract

Background Aggregations of nuclei within the syncytiotrophoblast cell layer of the placenta are increased in pre-eclampsia and intrauterine growth restriction (IUGR). Syncytial nuclear aggregates (SNAs) are described using various terms including: knots, sprouts and intervillous bridges. The authors aimed to investigate the structure of SNAs. Methods Placental villous tissue was fi xed and wax-embedded (n=7). Serial sections were stained with H&E. SNAs were defi ned as close groups of 10+ nuclei which protrude from, but do not touch another villus and intervillous bridges as groups of 10+ nuclei which touched another villus. The authors investigated the relative proportion of each. Apoptosis was assessed by staining for cytokeratin M30 and TUNEL. Cytoskeletal proteins including cytokeratin, α-, β-and γ-actin, α-and β-tubulin were detected by immunofl uorescence. Results 52.3% SNAs were intervillous bridges (IQR 48.8-54.4%), 18.6% were syncytial knots (14.1-35.1%) and 21.2% were other structures (12.6-33.0%). Between 73.5% and 80% of SNAs do not contain apoptotic nuclei, as tested by M30 and TUNEL respectively. Electron microscopy showed cytoskeletal proteins are found close to and sometimes encircling SNAs. Immunofl uorescence showed cytokeratin to be associated with SNAs. α-tubulin, β-tubulin, β-actin and γ-actin were found in syncytiotrophoblast but not SNAs. Conclusion The majority of SNAs are intervillous bridges. Cytoskeletal proteins were found in and close to SNAs suggesting a role in nuclear aggregation. Fewer SNAs than expected contained dying fragments of trophoblast. Further research is needed to understand how nuclei move into SNAs and why they are increased in placental pathologies such as IUGR.