Dataset Information

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

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.

SUBMITTER: Inagaki M

PROVIDER: S-EPMC7225742 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Inagaki Mai M Nishimura Tomohiro T Nakanishi Takeo T Shimada Hiroaki H Noguchi Saki S Akanuma Shin-Ichi SI Tachikawa Masanori M Hosoya Ken-Ichi KI Tamai Ikumi I Nakashima Emi E Tomi Masatoshi M

iScience 20200427 5

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 parturi ...[more]

PMID: 32408168

Similar Datasets

Project description:BackgroundBecause prostaglandins are involved in many (patho)physiological processes, SLCO2A1 was already characterized in several species in an attempt to unravel specific processes/deficiencies. Here, we describe the molecular cloning and characterization of the porcine ortholog in order to evaluate its possible involvement in F4 enterotoxigenic E. coli mediated neonatal diarrhoea, based on a positional candidate gene approach study.ResultsPorcine SLCO2A1 is organized in 14 exons, containing an open reading frame of 1935 bp, encoding a 12-transmembrane organic anion cell surface transporter of 644 aa. The -388 to -5 upstream region comprises a (CpG)48 island containing a number of conserved promoter elements, including a TATA box. A potential alternative promoter region was found in the conserved -973 to -700 upstream region. No consensus polyadenylation signal was discovered in the 3' UTR. Repeat sequences were found in 15% of all the non coding sequences.As expected for a multifunctional protein, a wide tissue distribution was observed. mRNA expression was found in the adrenal gland, bladder, caecum, colon (centripetal coil/centrifugal coil), diaphragm, duodenum, gallbladder, heart, ileum, jejunum, kidney, liver, longissimus dorsi muscle, lung, lymph node, mesenterium, rectum, spleen, stomach, tongue and ureter, but not in the aorta, oesophagus and pancreas.The promoter region and the exons (including the splice sites) of SLCO2A1 were resequenced in 5 F4ab/ac receptor positive and 5 F4ab/ac receptor negative pigs. Two silent and 2 missense (both S --> L at position 360 and 633) mutations were found, but none was associated with the F4ab/ac receptor phenotype. In addition, no phenotype associated differential mRNA expression or alternative/abberant splicing/polyadenylation was found in the jejunum.ConclusionThe molecular cloning and characterization of porcine SLCO2A1 not only contributes to the already existing knowledge about the transporter in general, but enables studies on porcine prostaglandin related processes/deficiencies as patient and/or model. Here we examined its possible involvement as receptor in F4 enterotoxigenic E. coli mediated neonatal diarrhoea. Because no phenotype associated differences could be found in the gene sequence nor in its jejunal transcription profile of F4ab/ac receptor positive/negative pigs, SLCO2A1 can most likely be excluded as receptor for F4 bacteria.

Project description:Objective This study aimed to evaluate maternal and neonatal outcomes by method of cervical ripening for labor induction among low-risk nulliparous individuals.Study design This is a secondary analysis of a multicenter randomized trial of labor induction at 39 weeks versus expectant management in low-risk nulliparous participants. Participants undergoing cervical ripening for labor induction in either group were included. Participants were excluded for preripening membrane rupture, abruption, chorioamnionitis, fetal demise, or cervical dilation ≥3.5 cm. Cervical ripening was defined by the initial method used: prostaglandin only (PGE; referent), Foley with concurrent prostaglandin (Foley-PGE), Foley only (Foley), and Foley with concurrent oxytocin (Foley-oxytocin). Coprimary outcomes were adverse maternal and neonatal composites. Secondary outcomes included cesarean delivery and length of labor and delivery (L&D) stay. Multivariable analysis was used to adjust for patient characteristics.Results Of 6,106 participants included in the trial, 2,376 (38.9%) met criteria for this analysis. Of these, 1,247 (52.4%) had cervical ripening with PGE, 290 (12.2%) had Foley-PGE, 385 (16.2%) had Foley, and 454 (19.1%) had Foley-oxytocin. The maternal composite outcome was similar among participants who received Foley-PGE (24.1%, adjusted relative risk [aRR] = 1.21, 95% confidence interval [CI]: 0.96-1.52), Foley (21.3%, aRR = 1.16, 95% CI: 0.92-1.45), or Foley-oxytocin (19.4%, aRR = 1.04, 95% CI: 0.83-1.29), compared with PGE (19.7%). The neonatal composite outcome was less frequent in participants who received the Foley-PGE (2.4%, aRR = 0.35, 95% CI: 0.16-0.75) or Foley (3.6%, aRR = 0.51, 95% CI: 0.29-0.89) but did not reach statistical significance for participants who received Foley-oxytocin (4.6%, aRR = 0.63, 95% CI: 0.40-1.01) compared with PGE only (6.8%). Participants who received Foley-PGE or Foley-oxytocin had a shorter L&D stay (adjusted mean difference = -1.97 hours, 95% CI: -3.45 to -0.49 and -5.92 hours, 95% CI: -7.07 to -4.77, respectively), compared with PGE.Conclusion In term low-risk nulliparous participants, Foley alone or concurrent with PGE is associated with a lower risk of adverse neonatal outcomes than with PGE alone. Length of L&D stay was the shortest with concurrent Foley-oxytocin.Key points· Adverse maternal outcomes are similar among different methods of cervical ripening in low-risk women.. · Adverse neonatal outcomes are less frequent with use of Foley alone or in combination with PGE.. · The use of Foley alone, or in combination with other agents, appears to be beneficial..

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets