Syncytial nuclear aggregates as markers for villous maturation in placentas from preterm birth

  • Madita Reimer

Abstract

The syncytiotrophoblast is the multinucleated syncytial layer lining the placental villi. In some areas nuclei form aggregates termed true knots by the process of trophoblast turnover. Thereby, the underlying cytotrophoblast cells proliferate, differentiate and fuse with the overlying synctiotrophoblast cells which have no own generative potency. The nuclei in the syncytiotrophoblast are undergoing apoptosis and form true knots which are shed into the maternal circulation as syncytiotrophoblast microparticles (STBMs). This process ensures that the diffusion distance between maternal and foetal blood is decreased to nourish the growing foetus. Excessive formation of true knots has been reported in placentas of pregnancies complicated by pre-eclampsia. This is a complication of pregnancy characterized by increased maternal blood pressure and induced preterm labour is the only treatment. Pregnancies complicated by chorioamnionitis, a severe inflammation of the foetal membranes due to a bacterial infection, are also at increased risk of preterm labour. The aim of this study is to establish an objective scoring system for placental villous maturation based on true knots, STBMs and syncytial knotting frequency. Our assumption is that the frequency of syncytial knots in placentas complicated by pre-eclampsia are increased. True knots, STBMs and syncytial knotting are assessed by histological examination of placental tissue using a light microscope. In pre-eclamptic placentas the highest numbers of true knots, syncytial knotting and STBMs compared to an idiopathic preterm control group were found. Placentas complicated by chorioamnionitis show a slight decrease of true knots, syncytial knotting and STBMs compared to the idiopathic preterm group and a significant decrease compared to pre-eclamptic placentas. The increase of true knots and syncytial knotting could be a sign for an increased trophoblast turnover during pre-eclampsia. This implies enhanced proliferation, differentiation and apoptosis of the placental epithelium. Chorioamnionitis placentas display lower number of true knots indicating a lower trophoblast turnover which may be part of another anomaly of the placental development. For our scoring system are true knots, STBMs and syncytial knotting convincing markers for analysis of villous maturation in pre-eclampsia. In case of chorioamnionitis other markers may be more useful.

References

Singh V. Textbook of Clinical Embryology: Elsevier Health Sciences APAC; 2014.

Benirschke K, Kaufmann P, Baergen RN. Pathology of the Human Placenta, 5th Edition: Springer; 2006.

Carlson BM. Human Embryology and Developmental Biology. 5 ed: Elsevier Health Sciences; 2012.

Fogarty NM, Mayhew TM, Ferguson-Smith AC, Burton GJ. A quantitative analysis of transcriptionally active syncytiotrophoblast nuclei across human gestation. J Anat. 2011;219(5):601-10.

Huppertz B. Placental villous trophoblast: the altered balance between proliferation and apoptosis triggers pre-eclampsia. Journal für Reproduktionsmedizin und Endokrinologie-Journal of Reproductive Medicine and Endocrinology. 2006;3(2):103-8.

Fox H. The significance of villous syncytial knots in the human placenta. J Obstet Gynaecol Br Commonw. 1965;72:347-55.

Jones CJ, Fox H. Syncytial knots and intervillous bridges in the human placenta: an ultrastructural study. Journal of Anatomy. 1977;124(Pt 2):275-86.

Kubli F, Budliger H. Contribution to the morphology of placental insufficiency. Geburtshilfe Frauenheilkd. 1963;23:37-43.

Tenney B, Parker F. The placenta in toxemia of pregnancy. Am J Obstet Gynecol. 1940;39:1000-5.

Calvert SJ, Jones CJP, Sibley CP, Aplin JD, Heazell AEP. Analysis of syncytial nuclear aggregates in preeclampsia shows increased sectioning artefacts and decreased inter-villous bridges compared to healthy placentas. Placenta. 2013;34(12):1251-4.

Naeye RL. Functionally important disorders of the placenta, umbilical cord, and fetal membranes. Human pathology. 1987;18(7):680-91.

Grether JK, Eaton A, Redline R, Bendon R, Benirschke K, Nelson K. Reliability of placental histology using archived specimens. Paediatr Perinat Epidemiol. 1999;13(4):489-95.

Stark MW, Clark L, Craver RD. Histologic Differences in Placentas of Preeclamptic/Eclamptic Gestations by Birthweight, Placental Weight, and Time of Onset. Pediatric and Developmental Pathology. 2014;17(3):181-9.

Ruiz-Quinonez G, Reza-Lopez SA, Chavez-Corral DV, Sanchez-Ramirez B, Leal-Berumen I, Levario-Carrillo M. Placental maturity, hypertensive disorders of pregnancy and birth weight. Hypertens Pregnancy. 2014;33(2):132-44.

Rayburn W, Sander C, Barr M, Jr., Rygiel R. The stillborn fetus: placental histologic examination in determining a cause. Obstet Gynecol. 1985;65(5):637-41.

Huppertz B, Kaufmann P, Kingdom J. Trophoblast turnover in health and disease. Fetal and Maternal Medicine Review. 2002;13(02):103-18.

Heazell AEP, Moll SJ, Jones CJP, Baker PN, Crocker IP. Formation of Syncytial Knots is Increased by Hyperoxia, Hypoxia and Reactive Oxygen Species. Placenta. 2007;28, Supplement(0):S33-S40.

Morgan TK, Tolosa JE, Mele L, Wapner RJ, Spong CY, Sorokin Y, et al. Placental villous hypermaturation is associated with idiopathic preterm birth. The Journal of Maternal-Fetal & Neonatal Medicine. 2012;26(7):647-53.

Published
2016-12-19