Szilvia Szabo1, Katalin Karaszi2, Roberto Romero3, Eszter Toth4, Andras Szilagyi4, Zsolt Gelencser4, Yi Xu5, Andrea Balogh4, Gabor Szalai4, Petronella Hupuczi6, Beata Hargitai7, Tibor Krenacs8, Eva Hunyadi-Gulyas9, Zsuzsanna Darula9, Katalin A Kekesi10, Adi L Tarca11, Offer Erez12, Gabor Juhasz13, Ilona Kovalszky8, Zoltan Papp6, Nandor Gabor Than14. 1. Systems Biology of Reproduction Lendulet Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary; Department of Morphology and Physiology, Faculty of Health Sciences, Semmelweis University, Budapest, Hungary. Electronic address: csorgo.szilvi@gmail.com. 2. Systems Biology of Reproduction Lendulet Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary; First Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary. Electronic address: tika0604@gmail.com. 3. Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, Maryland, and Detroit, MI, USA; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, USA; Detroit Medical Center, Detroit, MI, USA; Department of Obstetrics and Gynecology, Florida International University, Miami, FL, USA. 4. Systems Biology of Reproduction Lendulet Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary. 5. Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, Maryland, and Detroit, MI, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA. 6. Maternity Private Clinic of Obstetrics and Gynecology, Budapest, Hungary. 7. West Midlands Perinatal Pathology Centre, Cellular Pathology Department, Birmingham Women's and Children's NHS FT, Birmingham, United Kingdom. 8. First Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary. 9. Institute of Biochemistry, Biological Research Centre, Szeged, Hungary. 10. Department of Physiology and Neurobiology, ELTE Eotvos Lorand University, Budapest, Hungary; Laboratory of Proteomics, Institute of Biology, ELTE Eotvos Lorand University, Budapest, Hungary. 11. Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, Maryland, and Detroit, MI, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA; Department of Computer Science, Wayne State University College of Engineering, Detroit, MI, USA. 12. Perinatology Research Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, United States Department of Health and Human Services, Bethesda, Maryland, and Detroit, MI, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA; Maternity Department "D," Division of Obstetrics and Gynecology, Soroka University Medical Center, School of Medicine, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel. 13. Laboratory of Proteomics, Institute of Biology, ELTE Eotvos Lorand University, Budapest, Hungary; CRU Hungary Ltd., God, Hungary. 14. Systems Biology of Reproduction Lendulet Research Group, Institute of Enzymology, Research Centre for Natural Sciences, Budapest, Hungary; First Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary; Maternity Private Clinic of Obstetrics and Gynecology, Budapest, Hungary. Electronic address: than.gabor@ttk.hu.
Abstract
INTRODUCTION: Placental Protein 1 (PP1), PP8, and PP22 were isolated from the placenta. Herein, we aimed to identify PP1, PP8, and PP22 proteins and their placental and trophoblastic expression patterns to reveal potential involvement in pregnancy complications. METHODS: We analyzed PP1, PP8, and PP22 proteins with LC-MS. We compared the placental behaviors of PP1, PP8, and PP22 to the predominantly placenta-expressed PP5/TFPI-2. Placenta-specificity scores were generated from microarray data. Trophoblasts were isolated from healthy placentas and differentiated; total RNA was isolated and subjected to microarray analysis. We assigned the placentas to the following groups: preterm controls, early-onset preeclampsia, early-onset preeclampsia with HELLP syndrome, term controls, and late-onset preeclampsia. After histopathologic examination, placentas were used for tissue microarray construction, immunostaining with anti-PP1, anti-PP5, anti-PP8, or anti-PP22 antibodies, and immunoscoring. RESULTS: PP1, PP8, and PP22 were identified as 'nicotinate-nucleotide pyrophosphorylase', 'serpin B6', and 'protein disulfide-isomerase', respectively. Genes encoding PP1, PP8, and PP22 are not predominantly placenta-expressed, in contrast with PP5. PP1, PP8, and PP22 mRNA expression levels did not increase during trophoblast differentiation, in contrast with PP5. PP1, PP8, and PP22 immunostaining were detected primarily in trophoblasts, while PP5 expression was restricted to the syncytiotrophoblast. The PP1 immunoscore was higher in late-onset preeclampsia, while the PP5 immunoscore was higher in early-onset preeclampsia. DISCUSSION: PP1, PP8, and PP22 are expressed primarily in trophoblasts but do not have trophoblast-specific regulation or functions. The distinct dysregulation of PP1 and PP5 expression in either late-onset or early-onset preeclampsia reflects different pathophysiological pathways in these preeclampsia subsets.
INTRODUCTION:Placental Protein 1 (PP1), PP8, and PP22 were isolated from the placenta. Herein, we aimed to identify PP1, PP8, and PP22 proteins and their placental and trophoblastic expression patterns to reveal potential involvement in pregnancy complications. METHODS: We analyzed PP1, PP8, and PP22 proteins with LC-MS. We compared the placental behaviors of PP1, PP8, and PP22 to the predominantly placenta-expressed PP5/TFPI-2. Placenta-specificity scores were generated from microarray data. Trophoblasts were isolated from healthy placentas and differentiated; total RNA was isolated and subjected to microarray analysis. We assigned the placentas to the following groups: preterm controls, early-onset preeclampsia, early-onset preeclampsia with HELLP syndrome, term controls, and late-onset preeclampsia. After histopathologic examination, placentas were used for tissue microarray construction, immunostaining with anti-PP1, anti-PP5, anti-PP8, or anti-PP22 antibodies, and immunoscoring. RESULTS:PP1, PP8, and PP22 were identified as 'nicotinate-nucleotide pyrophosphorylase', 'serpin B6', and 'protein disulfide-isomerase', respectively. Genes encoding PP1, PP8, and PP22 are not predominantly placenta-expressed, in contrast with PP5. PP1, PP8, and PP22 mRNA expression levels did not increase during trophoblast differentiation, in contrast with PP5. PP1, PP8, and PP22 immunostaining were detected primarily in trophoblasts, while PP5 expression was restricted to the syncytiotrophoblast. The PP1 immunoscore was higher in late-onset preeclampsia, while the PP5 immunoscore was higher in early-onset preeclampsia. DISCUSSION: PP1, PP8, and PP22 are expressed primarily in trophoblasts but do not have trophoblast-specific regulation or functions. The distinct dysregulation of PP1 and PP5 expression in either late-onset or early-onset preeclampsia reflects different pathophysiological pathways in these preeclampsia subsets.