摘要：SummaryWe evaluated the contribution of organic anion transporting polypeptide 2A1 (OATP2A1/SLCO2A1), a high-affinity carrier for prostaglandins (PGs), to the parturition process. At gestational day (GD) 15.5, OATP2A1 is co-localized with 15-hydroxy-PG dehydrogenase in the mouse placental junctional zone and facilitates PG degradation by delivering PGs to the cytoplasm.Slco2a1(+/−) females mated withSlco2a1(−/−) males frequently showed elevated circulating progesterone at GD18.5 and delayed parturition. Progesterone receptor inhibition by RU486 treatment at GD18.5 blocked the delay of parturition. In the junctional zone, PGE2stimulated placental lactogen II (PL-II) production, resulting in higher expression of PL-II inSlco2a1(−/−) placenta at GD18.5. Indomethacin treatment at GD15.5 suppressed the PL-II overproduction at GD18.5 inSlco2a1(−/−) embryo-bearing dams, which promoted progesterone withdrawal and corrected the delayed parturition. These results suggest that extracellular PGE2reduction by OATP2A1 at mid-pregnancy would be associated with progesterone withdrawal by suppressing PL-II production, triggering parturition onset.Graphical AbstractDisplay OmittedHighlights•Placental OATP2A1 promotes PGE2degradation by delivering PGE2to the cytoplasm•Placental PGE2stimulates the PL-II production•Extracellular PGE2decrease by placental OATP2A1 promotes progesterone withdrawal•Feto-placental OATP2A1 is associated with the initiation of parturitionMolecular Biology; Endocrinology
