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dc.contributor.authorUllah, Rahim
dc.contributor.authorDar, Saira
dc.contributor.authorAhmad, Tanvir
dc.contributor.authorde Renty, Christelle
dc.contributor.authorUsman, Mohammad
dc.contributor.authorDePamphilis, Melvin L.
dc.contributor.authorFaisal, Amir
dc.contributor.authorShahzad-ul-Hussan, Syed
dc.contributor.authorUllah, Zakir
dc.date.accessioned2018-05-21T13:35:46Z
dc.date.available2018-05-21T13:35:46Z
dc.date.issued2018-05-17
dc.identifier.citationUllah R, Dar S, Ahmad T, de Renty C, Usman M, et al. (2018) CDK1 inhibition facilitates formation of syncytiotrophoblasts and expression of human Chorionic Gonadotropin. Placenta 66: 57–64. Available: http://dx.doi.org/10.1016/j.placenta.2018.05.003.
dc.identifier.issn0143-4004
dc.identifier.doi10.1016/j.placenta.2018.05.003
dc.identifier.urihttp://hdl.handle.net/10754/627926
dc.description.abstractAims The human placental syncytiotrophoblast (STB) cells play essential roles in embryo implantation and nutrient exchange between the mother and the fetus. STBs are polyploid which are formed by fusion of diploid cytotrophoblast (CTB) cells. Abnormality in STBs formation can result in pregnancy-related disorders. While a number of genes have been associated with CTB fusion the initial events that trigger cell fusion are not well understood. Primary objective of this study was to enhance our understanding about the molecular mechanism of placental cell fusion. Methods FACS and microscopic analysis was used to optimize Forskolin-induced fusion of BeWo cells (surrogate of CTBs) and subsequently, changes in the expression of different cell cycle regulator genes were analyzed through Western blotting and qPCR. Immunohistochemistry was performed on the first trimester placental tissue sections to validate the results in the context of placental tissue. Effect of Cyclin Dependent Kinase 1 (CDK1) inhibitor, RO3306, on BeWo cell fusion was studied by microscopy and FACS, and by monitoring the expression of human Chorionic Gonadotropin (hCG) by Western blotting and qPCR. Results The data showed that the placental cell fusion was associated with down regulation of CDK1 and its associated cyclin B, and significant decrease in DNA replication. Moreover, inhibition of CDK1 by an exogenous inhibitor induced placental cell fusion and expression of hCG. Conclusion Here, we report that the placental cell fusion can be induced by inhibiting CDK1. This study has a high therapeutic significance to manage pregnancy related abnormalities.
dc.description.sponsorshipThe project was primarily supported by the faculty initiative fund by Lahore University of Management Sciences and part of the work done at NIH was supported by intramural research program of NIH.
dc.publisherElsevier BV
dc.relation.urlhttps://www.sciencedirect.com/science/article/pii/S0143400418302285
dc.rightsNOTICE: this is the author’s version of a work that was accepted for publication in Placenta. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Placenta, [, , (2018-05-17)] DOI: 10.1016/j.placenta.2018.05.003 . © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectCDK1
dc.subjectCyclin
dc.subjectSyncytiotrophoblast
dc.subjectCell fusion
dc.subjectPlacenta
dc.subjecthCG
dc.titleCDK1 inhibition facilitates formation of syncytiotrophoblasts and expression of human Chorionic Gonadotropin
dc.typeArticle
dc.identifier.journalPlacenta
dc.eprint.versionPost-print
dc.contributor.institutionDepartment of Biology, SBA School of Science and Engineering, Lahore University of Management Sciences (LUMS), Opposite Sector U, DHA, Lahore, 54792, Pakistan
dc.contributor.institutionEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892, USA
dc.contributor.institutionFMH College of Medicine & Dentistry, Lahore, Pakistan
kaust.personUllah, Zakir


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