C M Duzyj1, I A Buhimschi2, C A Laky3, G Cozzini4, G Zhao2, M Wehrum5, C S Buhimschi6. 1. Department of Obstetrics, Gynecology and Reproductive Sciences, Rutgers University Robert Wood Johnson School of Medicine, New Brunswick, NJ, USA. 2. Center for Perinatal Research, Department of Pediatrics, The Research Institute at Nationwide Children's Hospital, The Ohio State University College of Medicine, Columbus, OH, USA. 3. Maternal Fetal Medicine, Mary Washington Hospital, Fredericksburg, VA, USA. 4. Americorps Communities in Schools Central Texas, Austin, TX, USA. 5. Maternal-Fetal Care Center, Florida Hospital Medical Group, Orlando, FL, USA. 6. Department of Obstetrics & Gynecology, The Ohio State University College of Medicine, Columbus, OH, USA.
Abstract
OBJECTIVE: Placenta accreta is clinically associated with maternal uterine scar. Our objective was to investigate the biochemical contribution of maternal scarring to hyperinvasive trophoblast. We hypothesised that trophoblast over-invasion in placenta accreta is associated with aberrant invasion-site signalling of growth and angiogenic factors known to be involved in wound healing and promotion of cell invasion through the epithelial to mesenchymal cellular programme. DESIGN: Cross-sectional series. SETTING: Yale-New Haven Hospital. POPULATION: Women with histologically confirmed normal and abnormal placentation. METHODS: Placental invasion site tissue sections were immunostained for endoglin and other angiogenic regulators, and transforming growth factor β (TGFβ) proteins. Maternal serum endoglin, and the vascular endothelial growth factor (VEGF) mediators hypoxia-inducible factor-1α (HIF1α) and endostatin, were assessed using immunoassay. MAIN OUTCOME MEASURES: Differences in median H-score by immunostaining and in mean serum level by immunoassay. RESULTS: By immunostaining, placenta accreta samples demonstrated intervillous endoglin shedding and increased trophoblast expression of its cleavage protein matrix metalloproteinase-14. Absent decidual HIF1α and endostatin were observed in areas of VEGF upregulation. TGFβ1 was present in myocytes but not in collagen bundles into which accreta trophoblast invaded. Maternal serum endoglin decreased in praevia and accreta when corrected for gestational age. CONCLUSION: Angiogenic and growth factors at the placental invasion site are altered in accreta, both by decidual absence and within myometrial scar. We postulate this promotes the invasive phenotype of placenta accreta by activating hyperinvasive trophoblast and by dysregulating placental vascular remodelling. FUNDING: Yale Department of Obstetrics, Gynecology and Reproductive Sciences funds. TWEETABLE ABSTRACT: Placenta accreta histology shows dysregulation of angiogenic and growth factors.
OBJECTIVE: Placenta accreta is clinically associated with maternal uterine scar. Our objective was to investigate the biochemical contribution of maternal scarring to hyperinvasive trophoblast. We hypothesised that trophoblast over-invasion in placenta accreta is associated with aberrant invasion-site signalling of growth and angiogenic factors known to be involved in wound healing and promotion of cell invasion through the epithelial to mesenchymal cellular programme. DESIGN: Cross-sectional series. SETTING: Yale-New Haven Hospital. POPULATION: Women with histologically confirmed normal and abnormal placentation. METHODS: Placental invasion site tissue sections were immunostained for endoglin and other angiogenic regulators, and transforming growth factor β (TGFβ) proteins. Maternal serum endoglin, and the vascular endothelial growth factor (VEGF) mediators hypoxia-inducible factor-1α (HIF1α) and endostatin, were assessed using immunoassay. MAIN OUTCOME MEASURES: Differences in median H-score by immunostaining and in mean serum level by immunoassay. RESULTS: By immunostaining, placenta accreta samples demonstrated intervillous endoglin shedding and increased trophoblast expression of its cleavage protein matrix metalloproteinase-14. Absent decidual HIF1α and endostatin were observed in areas of VEGF upregulation. TGFβ1 was present in myocytes but not in collagen bundles into which accreta trophoblast invaded. Maternal serum endoglin decreased in praevia and accreta when corrected for gestational age. CONCLUSION: Angiogenic and growth factors at the placental invasion site are altered in accreta, both by decidual absence and within myometrial scar. We postulate this promotes the invasive phenotype of placenta accreta by activating hyperinvasive trophoblast and by dysregulating placental vascular remodelling. FUNDING: Yale Department of Obstetrics, Gynecology and Reproductive Sciences funds. TWEETABLE ABSTRACT: Placenta accreta histology shows dysregulation of angiogenic and growth factors.
Authors: Jelena Krstic; Alexander Deutsch; Julia Fuchs; Martin Gauster; Tina Gorsek Sparovec; Ursula Hiden; Julian Christopher Krappinger; Gerit Moser; Katrin Pansy; Marta Szmyra; Daniela Gold; Julia Feichtinger; Berthold Huppertz Journal: Biomedicines Date: 2022-05-04