Placenta-Specific Genes, Their Regulation During Villous Trophoblast Differentiation and Dysregulation in Preterm Preeclampsia
by
Andras Szilagyi 1,†
, Zsolt Gelencser 1,†, Roberto Romero 2,3,4,5,6,7, Yi Xu 2,8, Peter Kiraly 1, Amanda Demeter 1, Janos Palhalmi 1, Balazs A. Gyorffy 9, Kata Juhasz 1, Petronella Hupuczi 10, Katalin Adrienna Kekesi 9,11, Gudrun Meinhardt 12, Zoltan Papp 10,13, Sorin Draghici 14, Offer Erez 2,8,15, Adi Laurentiu Tarca 2,5,8, Martin Knöfler 12 and Nandor Gabor Than 1,2,8,10,16,*
Andras Szilagyi 1,†, Zsolt Gelencser 1,†, Roberto Romero 2,3,4,5,6,7, Yi Xu 2,8, Peter Kiraly 1, Amanda Demeter 1, Janos Palhalmi 1, Balazs A. Gyorffy 9, Kata Juhasz 1, Petronella Hupuczi 10, Katalin Adrienna Kekesi 9,11, Gudrun Meinhardt 12, Zoltan Papp 10,13, Sorin Draghici 14, Offer Erez 2,8,15, Adi Laurentiu Tarca 2,5,8, Martin Knöfler 12 and Nandor Gabor Than 1,2,8,10,16,*
1
Systems Biology of Reproduction Lendulet Group, Institute of Enzymology, Research Centre for Natural Sciences, H-1117 Budapest, Hungary
2
Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, MD 20692, and Detroit, MI 48201, USA
3
Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI 48109, USA
4
Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI 48824, USA
5
Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA
6
Detroit Medical Center, Detroit, MI 48201, USA
7
Department of Obstetrics and Gynecology, Florida International University, Miami, FL 33199, USA
8
Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA
9
Laboratory of Proteomics, Institute of Biology, Eotvos Lorand University, H-1117 Budapest, Hungary
10
Maternity Private Clinic of Obstetrics and Gynecology, H-1126 Budapest, Hungary
11
Department of Physiology and Neurobiology, Eotvos Lorand University, H-1117 Budapest, Hungary
12
Department of Obstetrics and Gynecology, Reproductive Biology Unit, Medical University of Vienna, Vienna A-1090, Austria
13
Department of Obstetrics and Gynecology, Semmelweis University, H-1088 Budapest, Hungary
14
Department of Computer Science, Wayne State University College of Engineering, Detroit, MI 48202, USA
15
Department of Obstetrics and Gynecology, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel
16
1st Department of Pathology and Experimental Cancer Research, Semmelweis University, H-1085 Budapest, Hungary
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(2), 628; https://doi.org/10.3390/ijms21020628
Received: 3 December 2019 / Revised: 7 January 2020 / Accepted: 8 January 2020 / Published: 17 January 2020
(This article belongs to the Special Issue Pathogenesis of Pregnancy-Related Complications)
The human placenta maintains pregnancy and supports the developing fetus by providing nutrition, gas-waste exchange, hormonal regulation, and an immunological barrier from the maternal immune system. The villous syncytiotrophoblast carries most of these functions and provides the interface between the maternal and fetal circulatory systems. The syncytiotrophoblast is generated by the biochemical and morphological differentiation of underlying cytotrophoblast progenitor cells. The dysfunction of the villous trophoblast development is implicated in placenta-mediated pregnancy complications. Herein, we describe gene modules and clusters involved in the dynamic differentiation of villous cytotrophoblasts into the syncytiotrophoblast. During this process, the immune defense functions are first established, followed by structural and metabolic changes, and then by peptide hormone synthesis. We describe key transcription regulatory molecules that regulate gene modules involved in placental functions. Based on transcriptomic evidence, we infer how villous trophoblast differentiation and functions are dysregulated in preterm preeclampsia, a life-threatening placenta-mediated obstetrical syndrome for the mother and fetus. In the conclusion, we uncover the blueprint for villous trophoblast development and its impairment in preterm preeclampsia, which may aid in the future development of non-invasive biomarkers for placental functions and early identification of women at risk for preterm preeclampsia as well as other placenta-mediated pregnancy complications.
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Keywords:
development; immune tolerance; metabolism; microarray; omics; transcriptional network
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MDPI and ACS Style
Szilagyi, A.; Gelencser, Z.; Romero, R.; Xu, Y.; Kiraly, P.; Demeter, A.; Palhalmi, J.; Gyorffy, B.A.; Juhasz, K.; Hupuczi, P.; Kekesi, K.A.; Meinhardt, G.; Papp, Z.; Draghici, S.; Erez, O.; Tarca, A.L.; Knöfler, M.; Than, N.G. Placenta-Specific Genes, Their Regulation During Villous Trophoblast Differentiation and Dysregulation in Preterm Preeclampsia. Int. J. Mol. Sci. 2020, 21, 628.
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