High 3-hydroxybutyrate concentrations in the placenta-produced amniotic fluid in the human uterus

In this study, we report first high concentrations of a ketone body, 3-hydroxybutyrate (3HB) in the amniotic fluid in humans. Although 3HB concentrations in the maternal blood are approximately 0.1, those in the amniotic fluid are approximately 0.6 mM. High placental 3HB production is potentially key for producing and maintaining high 3HB levels in the amniotic fluid. The rate-limiting enzyme, mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), is highly expressed in the cells of the chorionic plate and responsible for 3HB production. Therefore, high HMGCS2 expression maintenance is supposed to be pivotal for maintaining the 3HB supply for the human fetus. Here, we propose that humans display two pathways, an amniotic fluid- and another umbilical vein-mediated, for supplying 3HB to the human fetus. These supply pathways are supposedly essential for human brain development during the late phase of pregnancy. Graphical abstractHuman fetuses are supported by 3HB from the amniotic fluid for their brain development. HIGHLIGTS3-Hydroxybutyrate concentrations are high in the amniotic fluid in the human uterus. The chorionic plate of the placenta highly expresses 3-hydroxy-3-methylglutaryl-CoA synthase 2. Human fetuses may be supplied with 3HB for brain development through the amniotic fluid.