title: Cytotrophoblast, Not Syncytiotrophoblast, Dominates Glycolysis and Oxidative Phosphorylation in Human Term Placenta.
abstract: The syncytiotrophoblast (SCT) at the maternal-fetal interface has been presumed to be the primary driver of placental metabolism, and the underlying progenitor cytotrophoblast cells (CTB) an insignificant contributor to placental metabolic activity. However, we now show that the metabolic rate of CTB is much greater than the SCT. The oxygen consumption and extracellular acidification rate, a measure of glycolysis, are both greater in CTB than in SCT in vitro (CTB: 96 ± 16 vs SCT: 46 ± 14 pmol O2× min-1× 100 ng DNA-1, p < 0.001) and (CTB: 43 ± 6.7 vs SCT 1.4 ± 1.0 ∆mpH × min-1× 100 ng DNA-1, p < 0.0001). Mitochondrial activity, as determined by using the mitochondrial activity-dependent dye Mitotracker CM-H2TMRosa, is higher in CTB than in SCT in culture and living explants. These data cast doubt on the previous supposition that the metabolic rate of the placenta is dominated by the SCT contribution. Moreover, differentiation into SCT leads to metabolic suppression. The normal suppression of metabolic activity during CTB differentiation to SCT is prevented with a p38 MAPK signaling inhibitor and epidermal growth factor co-treatment. We conclude that the undifferentiated CTB, in contrast to the SCT, is highly metabolically active, has a high level of fuel flexibility, and contributes substantially to global metabolism in the late gestation human placenta.
authors.affiliation: Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR 97239 USA.|Center for Developmental Health, Knight Cardiovascular Institute Oregon Health and Science University, Portland, OR 97239 USA.
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Kolahi
authors.affiliation: Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR 97239 USA.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Valent
authors.affiliation: Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR 97239 USA.|Center for Developmental Health, Knight Cardiovascular Institute Oregon Health and Science University, Portland, OR 97239 USA.|Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR 97239 USA.
authors.forename: Kent L
authors.initials: KL
authors.lastname: Thornburg
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D064688:Metabolic Flux Analysis; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D011725:Pyridines / Q000494:pharmacology; D047929:Term Birth; D014327:Trophoblasts / Q000166:cytology / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D005230:Fatty Acids, Nonesterified; D007093:Imidazoles; D011725:Pyridines; D004815:Epidermal Growth Factor; D000255:Adenosine Triphosphate; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580