Contribution of Prostaglandin Transporter OATP2A1/SLCO2A1 to Placenta-to-Maternal Hormone Signaling and Labor Induction
Contribution of Prostaglandin Transporter OATP2A1/SLCO2A1 to Placenta-to-Maternal Hormone Signaling and Labor Induction
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DOI：
10.1016/j.isci.2020.101098
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发表时间：
2020-05-22
期刊：
影响因子：
5.8
通讯作者：
Tomi, Masatoshi
中科院分区：
文献类型：
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作者：
Inagaki, Mai;Nishimura, Tomohiro;Tomi, Masatoshi
我们评估了有机阴离子转运多肽2A 1（OATP 2A 1/SLCO 2A 1），一种高亲和力的前列腺素（PGs）载体，对分娩过程的贡献。在妊娠第15.5天（GD），OATP 2A 1与15-羟基- PG脱氢酶共定位于小鼠胎盘结合区，并通过将PG递送至细胞质促进PG降解。与Slco 2a 1（-/-）雄性交配的Slco 2a 1（+/-）雌性动物在GD 18.5时经常显示循环孕酮升高和分娩延迟。在GD 18.5，通过RU 486处理的孕激素受体抑制阻断了分娩延迟。在结合区，PGE（2）刺激胎盘催乳素II（PL-II）的产生，导致GD18.5时Slco 2a 1（-/-）胎盘中PL-II的表达增加。在GD15.5时给予吲哚美辛抑制了携带Slco 2a 1（-/-）胚胎的母鼠在GD18.5时PL-II的过度产生，这促进了孕酮的戒断并纠正了延迟分娩。这些结果表明，OATP 2A 1在妊娠中期减少细胞外PGE 2与通过抑制PL-II产生的孕酮戒断相关，从而触发分娩发作。
We 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 with Slco2a1 (-/-) 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, PGE(2) stimulated placental lactogen II (PL-II) production, resulting in higher expression of PL-II in Slco2a1 (-/-) placenta at GD18.5. Indomethacin treatment at GD15.5 suppressed the PL-II overproduction at GD18.5 in Slco2a1 (-/-) embryo-bearing dams, which promoted progesterone withdrawal and corrected the delayed parturition. These results suggest that extracellular PGE2 reduction by OATP2A1 at mid-pregnancy would be associated with progesterone withdrawal by suppressing PL-II production, triggering parturition onset.