title: Effects of Fetal Sex on Expression of the (Pro)renin Receptor and Genes Influenced by its Interaction With Prorenin in Human Amnion.
abstract: Males are more likely to be born preterm than females. The causes are unknown, but it is suggested that intrauterine tissues regulate fetal growth and survival in a sex-specific manner. We postulated that prorenin binding to its prorenin/renin receptor receptor (ATP6AP2) would act in a fetal sex-specific manner in human amnion to regulate the expression of promyelocytic zinc finger, a negative regulator of ATP6AP2 expression as well as 2 pathways that might influence the onset of labor, namely transforming growth factor β1 (TGFB1) and prostaglandin endoperoxide synthase 2 (PTGS2). Our findings demonstrate that there are strong interactions between prorenin, ATP6AP2, and TGFB1 and that this system has a greater capacity in female amnion to stimulate profibrotic pathways, thus maintaining the integrity of the fetal membranes. In contrast, glucocorticoids or other factors independent of the prorenin/prorenin receptor pathway may be important regulators of PTGS2 in human pregnancy.
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia Mothers and Babies Research Centre, Hunter Medical Research Institute, Newcastle, New South Wales, Australia kirsty.pringle@newcastle.edu.au.
authors.forename: Kirsty G
authors.initials: KG
authors.lastname: Pringle
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia Mothers and Babies Research Centre, Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
authors.forename: Alison
authors.initials: A
authors.lastname: Conquest
authors.affiliation: Mothers and Babies Research Centre, Hunter Medical Research Institute, Newcastle, New South Wales, Australia School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Mitchell
authors.affiliation: Mothers and Babies Research Centre, Hunter Medical Research Institute, Newcastle, New South Wales, Australia School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia.
authors.forename: Tamas
authors.initials: T
authors.lastname: Zakar
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia Mothers and Babies Research Centre, Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
authors.forename: Eugenie R
authors.initials: ER
authors.lastname: Lumbers
mesh_terms: D000650:Amnion / Q000187:drug effects / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008297:Male; D047928:Premature Birth / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012083:Renin / Q000378:metabolism*; D012307:Risk Factors; D012737:Sex Factors; D015398:Signal Transduction; D013997:Time Factors; D046509:Tissue Culture Techniques; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism*; D000093342:Prorenin Receptor
chemical_list: D051546:Cyclooxygenase 2; D003907:Dexamethasone; D005938:Glucocorticoids; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D012083:Renin; D053773:Transforming Growth Factor beta1; D025262:Vacuolar Proton-Translocating ATPases; C458319:ATP6AP2 protein, human; D000093342:Prorenin Receptor; C508960:TGFB1 protein, human; C092037:ZBTB16 protein, human; C496540:PTGS2 protein, human
keywords: amnion; prorenin; prorenin receptor; prostaglandin endoperoxide synthase 2; transforming growth factor