Poly (ADP-ribose) polymerase-1 (PARP-1) induces human trophoblast syncytialization
type: CreativeWork
description: The fetal component of the human placenta is comprised of cells termed trophoblasts and the proper differentiation of these cells is pivotal for maintaining maternal and fetal health throughout pregnancy. The placental syncytiotrophoblast layer is a key secretory portion of the placenta and is produced through fusion of underlying progenitor cytotrophoblast cells with the multinucleated syncytiotrophoblast layer. The MacPhee laboratory has previously established that fusion or syncytialization of cytotrophoblasts is aided by expression of integrin-linked kinase (ILK), a cytoplasmic adapter protein. Nuclear enzyme Poly ADP-ribose Polymerase-1 (PARP-1) and the transcriptional repressor Snail-1 work with ILK to downregulate epithelial cell-cell adhesion. This process would also be necessary for proper trophoblast syncytialization. Thus, it was hypothesized that PARP-1 would be an important mediator of syncytiotrophoblast development. To test this hypothesis, immunofluorescence analysis of PARP-1 and Snail expression in human chorionic villi from first and second trimester as well as from term pregnancy was conducted. Furthermore, co-localization between PARP-1 and Snail-1 were evaluated. Lastly, human PARP-1 was overexpressed in the BeWo trophoblast derived cell line, under fusion promoting conditions, to directly test the ability of PARP-1 to regulate trophoblast fusion. Throughout the first and second trimester, PARP-1 and Snail were highly expressed and co-localized in villous cytotrophoblast nuclei. In contrast, PARP-1 was rarely detectable in syncytiotrophoblast nuclei, while Snail was highly expressed. Upon transient overexpression of PARP-1 in BeWo cells, fusion was robustly promoted. Furthermore, the mean number of nuclei per syncytium was markedly higher in PARP-overexpressing cells compared to control cells. However, PARP-1 overexpression did not regulate trophoblast hormonal differentiation. In conclusion, PARP-1 does appear to be a key enzyme in the process…
abstract: The fetal component of the human placenta is comprised of cells termed trophoblasts and the proper differentiation of these cells is pivotal for maintaining maternal and fetal health throughout pregnancy. The placental syncytiotrophoblast layer is a key secretory portion of the placenta and is produced through fusion of underlying progenitor cytotrophoblast cells with the multinucleated syncytiotrophoblast layer. The MacPhee laboratory has previously established that fusion or syncytialization of cytotrophoblasts is aided by expression of integrin-linked kinase (ILK), a cytoplasmic adapter protein. Nuclear enzyme Poly ADP-ribose Polymerase-1 (PARP-1) and the transcriptional repressor Snail-1 work with ILK to downregulate epithelial cell-cell adhesion. This process would also be necessary for proper trophoblast syncytialization. Thus, it was hypothesized that PARP-1 would be an important mediator of syncytiotrophoblast development. To test this hypothesis, immunofluorescence analysis of PARP-1 and Snail expression in human chorionic villi from first and second trimester as well as from term pregnancy was conducted. Furthermore, co-localization between PARP-1 and Snail-1 were evaluated. Lastly, human PARP-1 was overexpressed in the BeWo trophoblast derived cell line, under fusion promoting conditions, to directly test the ability of PARP-1 to regulate trophoblast fusion. Throughout the first and second trimester, PARP-1 and Snail were highly expressed and co-localized in villous cytotrophoblast nuclei. In contrast, PARP-1 was rarely detectable in syncytiotrophoblast nuclei, while Snail was highly expressed. Upon transient overexpression of PARP-1 in BeWo cells, fusion was robustly promoted. Furthermore, the mean number of nuclei per syncytium was markedly higher in PARP-overexpressing cells compared to control cells. However, PARP-1 overexpression did not regulate trophoblast hormonal differentiation. In conclusion, PARP-1 does appear to be a key enzyme in the process…
author: Pater, Justin
language: eng
keywords: placenta, trophoblast, syncytialization, preterm birth
date published: 2013-12-04
date modified: 2026-07-24T04:27:06Z
provider: University of Saskatchewan
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Saskatchewan

PropertyValue
property ID: Handle
value: https://hdl.handle.net/10388/ETD-2013-10-1277