Contribution of Prostaglandin Transporter OATP2A1/SLCO2A1 to Placenta-to-Maternal Hormone Signaling and Labor Induction

Mai Inagaki; Tomohiro Nishimura; Takeo Nakanishi; Hiroaki Shimada; Saki Noguchi; Shin-Ichi Akanuma; Masanori Tachikawa; Ken-Ichi Hosoya; Ikumi Tamai; Emi Nakashima; Masatoshi Tomi

doi:10.1016/j.isci.2020.101098

Contribution of Prostaglandin Transporter OATP2A1/SLCO2A1 to Placenta-to-Maternal Hormone Signaling and Labor Induction

iScience. 2020 May 22;23(5):101098. doi: 10.1016/j.isci.2020.101098. Epub 2020 Apr 27.

Authors

Affiliations

¹ Faculty of Pharmacy, Keio University, Minato-ku, Tokyo 105-8512, Japan.
² Faculty of Pharmacy, Takasaki University of Health and Welfare, Takasaki, Gunma 370-0033, Japan; Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa 920-1192, Japan.
³ Faculty of Pharmacy, Kindai University, Higashiosaka, Osaka 577-8502, Japan.
⁴ Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan.
⁵ Graduate School of Biomedical Sciences, Tokushima University, Tokushima 770-8505, Japan.
⁶ Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa 920-1192, Japan.
⁷ Faculty of Pharmacy, Keio University, Minato-ku, Tokyo 105-8512, Japan. Electronic address: tomi-ms@pha.keio.ac.jp.

Abstract

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, PGE₂ 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.

Keywords: Endocrinology; Molecular Biology.