Richard Jones1, Juan Peña1, Elana Mystal1, Carmen Marsit2, Men-Jean Lee3, Joanne Stone4, Luca Lambertini1,4. 1. Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 2. Department of Environmental Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA. 3. Department of Obstetrics and Gynecology, Mount Sinai Beth Israel Hospital, New York, NY, USA. 4. Department of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Abstract
Introduction: Intrauterine growth restriction (IUGR) is a major pregnancy complication with significant postnatal implications. IUGR is characterized by high placental oxidative stress (OS) and increased mitochondrial DNA (mtDNA) abundance that altogether alter the placental metabolism. Such alterations may be captured by changes in the expression of mitochondrial-encoded oxidative phosphorylation genes and glycolysis-regulatory genes.Study design: We aimed here to determine the association between the placental expression of all 13 protein-coding mitochondrial-encoded genes and seven key nuclear glycolysis-regulatory genes, PDK1, PDK2, PDK3, PDK4, PKLR, PKM, OGT, with IUGR, within a case-control study including 50 IUGR and 100 control pregnancies. We additionally assessed placental mtDNA abundance and OS. Results: Three mitochondrial genes, MT-ND5, MT-ND6, and MT-ATP6 were found negatively associated with IUGR, while one glycolysis-regulatory gene, PDK1 was positively associated with IUGR. mtDNA abundance and OS were positively associated with IUGR. Our study confirmed the existing data on IUGR inducing increased placental OS and mtDNA abundance. Further, our data highlighted the significant involvement of mitochondria and glucose metabolism in the OS-challenged IUGR placentas, which might modulate the placental expression of genes affecting the OXPHOS and promoting glycolysis.Brief rationale: By using banked placenta samples available at Icahn School of Medicine at Mount Sinai, this study aims at laying the foundation for the characterization of the role of mitochondria epi/genetics in IUGR. IUGR is a highly prevalent pregnancy outcome with long-term effects on the progeny that, at present, has limited tools that can be used for its diagnosis and characterization, thus limiting the efficacy of both clinical and public health interventions. The alterations of mitochondrial copy number, OS and mitochondrial and glycolysis-regulatory gene expression that we detected, together, provide the first evidence that these phenomena are playing an important role in the pathophysiology of IUGR. These findings suggest possible new research paths for the full characterization of mitochondrial biomarkers of IUGR.
Introduction: Intrauterine growth restriction (IUGR) is a major pregnancy complication with significant postnatal implications. IUGR is characterized by high placental oxidative stress (OS) and increased mitochondrial DNA (mtDNA) abundance that altogether alter the placental metabolism. Such alterations may be captured by changes in the expression of mitochondrial-encoded oxidative phosphorylation genes and glycolysis-regulatory genes.Study design: We aimed here to determine the association between the placental expression of all 13 protein-coding mitochondrial-encoded genes and seven key nuclear glycolysis-regulatory genes, PDK1, PDK2, PDK3, PDK4, PKLR, PKM, OGT, with IUGR, within a case-control study including 50 IUGR and 100 control pregnancies. We additionally assessed placental mtDNA abundance and OS. Results: Three mitochondrial genes, MT-ND5, MT-ND6, and MT-ATP6 were found negatively associated with IUGR, while one glycolysis-regulatory gene, PDK1 was positively associated with IUGR. mtDNA abundance and OS were positively associated with IUGR. Our study confirmed the existing data on IUGR inducing increased placental OS and mtDNA abundance. Further, our data highlighted the significant involvement of mitochondria and glucose metabolism in the OS-challenged IUGR placentas, which might modulate the placental expression of genes affecting the OXPHOS and promoting glycolysis.Brief rationale: By using banked placenta samples available at Icahn School of Medicine at Mount Sinai, this study aims at laying the foundation for the characterization of the role of mitochondria epi/genetics in IUGR. IUGR is a highly prevalent pregnancy outcome with long-term effects on the progeny that, at present, has limited tools that can be used for its diagnosis and characterization, thus limiting the efficacy of both clinical and public health interventions. The alterations of mitochondrial copy number, OS and mitochondrial and glycolysis-regulatory gene expression that we detected, together, provide the first evidence that these phenomena are playing an important role in the pathophysiology of IUGR. These findings suggest possible new research paths for the full characterization of mitochondrial biomarkers of IUGR.
Authors: Colette N Miller; Janice A Dye; Andres R Henriquez; Erica J Stewart; Katelyn S Lavrich; Gleta K Carswell; Hongzu Ren; Danielle L Freeborn; Samantha J Snow; Mette C Schladweiler; Judy H Richards; Prasada R S Kodavanti; Anna Fisher; Brian N Chorley; Urmila P Kodavanti Journal: Mol Metab Date: 2020-10-05 Impact factor: 7.422
Authors: Miguel A Ortega; Miguel A Sáez; Oscar Fraile-Martínez; Miguel A Álvarez-Mon; Cielo García-Montero; Luis G Guijarro; Ángel Asúnsolo; Melchor Álvarez-Mon; Julia Bujan; Natalio García-Honduvilla; Juan A De León-Luis; Coral Bravo Journal: Int J Med Sci Date: 2022-01-01 Impact factor: 3.738