Uterine receptor activation in response to uterotonic agents in late-pregnancy rat myometrium following pretreatment with oxytocin: an in vitro study

Background: Long term exposure to oxytocin reduces the ability of myometrium to respond to oxytocin, leading to oxytocin receptor (OXTR) desensitization. In this study we analyzed the response to other uterotonics such as prostaglandin, as well as investigating prostaglandin E2 receptors (EP3) and p...

Full description

Saved in:
Bibliographic Details
Main Authors: Li-Mei Liao, Jian-Ying Hu, Ting-Ting Wang, Shao-Qiang Huang
Format: Article
Language:English
Published: IMR Press 2021-06-01
Series:Clinical and Experimental Obstetrics & Gynecology
Subjects:
Online Access:https://www.imrpress.com/journal/CEOG/48/3/10.31083/j.ceog.2021.03.2303
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849324894220713984
author Li-Mei Liao
Jian-Ying Hu
Ting-Ting Wang
Shao-Qiang Huang
author_facet Li-Mei Liao
Jian-Ying Hu
Ting-Ting Wang
Shao-Qiang Huang
author_sort Li-Mei Liao
collection DOAJ
description Background: Long term exposure to oxytocin reduces the ability of myometrium to respond to oxytocin, leading to oxytocin receptor (OXTR) desensitization. In this study we analyzed the response to other uterotonics such as prostaglandin, as well as investigating prostaglandin E2 receptors (EP3) and prostaglandin F2α receptors (FP). We hypothesized that compensatory mechanisms would increase the expression and activation of FP and EP3 following OXTR desensitization. Methods: Myometrium from late-pregnancy rats was collected in order to assess mRNA expression levels for OXTR, FP, and EP3 using RT-PCR. This was done after 2 hours of pretreatment with 10-6 M oxytocin to induce OXTR desensitization, or equilibration in physiological salt solution (PSS). Myometrium was exposed to increasing concentrations of uterotonic agents (10-10 to 10-5 M) following 2 hours of pretreatment with 10-6 M oxytocin (experimental group) or with PSS (control group). Myometrium from the experimental group was washed with PSS and OXTR expression was assessed using Western blot and RT-PCR. Results: mRNA expression levels for EP3, FP and OXTR were not statistically different between the experimental (OXTR desensitization) and control groups. Compared to the control group, the (mean ± SD) contractile potency of carboprost (pEC50: 7.74 ± 0.56 vs 6.81 ± 0.25, P = 0.03) and maximal contractility of misoprostol (Emax(ratio): 4.44 ± 3.60 vs 1.32 ± 0.22, P = 0.02) were significantly increased in the OXTR desensitization group, while the contractility of oxytocin was significantly reduced (Emax(ratio): 1.62 ± 0.27 vs 2.82 ± 0.98, P = 0.015). No significant differences in myometrial OXTR expression were observed between the PSS, carboprost and misoprostol groups following OXTR desensitization. Discussion: Following OXTR desensitization of myometrium, FP and EP3 activation increased in a compensatory manner, but not FP and EP3 receptor expression.
format Article
id doaj-art-dbd313bb2a3c4ec8a2d7e5de70c324ef
institution Kabale University
issn 0390-6663
language English
publishDate 2021-06-01
publisher IMR Press
record_format Article
series Clinical and Experimental Obstetrics & Gynecology
spelling doaj-art-dbd313bb2a3c4ec8a2d7e5de70c324ef2025-08-20T03:48:35ZengIMR PressClinical and Experimental Obstetrics & Gynecology0390-66632021-06-0148350050810.31083/j.ceog.2021.03.2303S0390-6663(21)00121-4Uterine receptor activation in response to uterotonic agents in late-pregnancy rat myometrium following pretreatment with oxytocin: an in vitro studyLi-Mei Liao0Jian-Ying Hu1Ting-Ting Wang2Shao-Qiang Huang3Department of Anaesthesia, Obstetrics & Gynecology Hospital, Fudan University, 200090 Shanghai, ChinaDepartment of Anaesthesia, Obstetrics & Gynecology Hospital, Fudan University, 200090 Shanghai, ChinaDepartment of Anaesthesia, Obstetrics & Gynecology Hospital, Fudan University, 200090 Shanghai, ChinaDepartment of Anaesthesia, Obstetrics & Gynecology Hospital, Fudan University, 200090 Shanghai, ChinaBackground: Long term exposure to oxytocin reduces the ability of myometrium to respond to oxytocin, leading to oxytocin receptor (OXTR) desensitization. In this study we analyzed the response to other uterotonics such as prostaglandin, as well as investigating prostaglandin E2 receptors (EP3) and prostaglandin F2α receptors (FP). We hypothesized that compensatory mechanisms would increase the expression and activation of FP and EP3 following OXTR desensitization. Methods: Myometrium from late-pregnancy rats was collected in order to assess mRNA expression levels for OXTR, FP, and EP3 using RT-PCR. This was done after 2 hours of pretreatment with 10-6 M oxytocin to induce OXTR desensitization, or equilibration in physiological salt solution (PSS). Myometrium was exposed to increasing concentrations of uterotonic agents (10-10 to 10-5 M) following 2 hours of pretreatment with 10-6 M oxytocin (experimental group) or with PSS (control group). Myometrium from the experimental group was washed with PSS and OXTR expression was assessed using Western blot and RT-PCR. Results: mRNA expression levels for EP3, FP and OXTR were not statistically different between the experimental (OXTR desensitization) and control groups. Compared to the control group, the (mean ± SD) contractile potency of carboprost (pEC50: 7.74 ± 0.56 vs 6.81 ± 0.25, P = 0.03) and maximal contractility of misoprostol (Emax(ratio): 4.44 ± 3.60 vs 1.32 ± 0.22, P = 0.02) were significantly increased in the OXTR desensitization group, while the contractility of oxytocin was significantly reduced (Emax(ratio): 1.62 ± 0.27 vs 2.82 ± 0.98, P = 0.015). No significant differences in myometrial OXTR expression were observed between the PSS, carboprost and misoprostol groups following OXTR desensitization. Discussion: Following OXTR desensitization of myometrium, FP and EP3 activation increased in a compensatory manner, but not FP and EP3 receptor expression.https://www.imrpress.com/journal/CEOG/48/3/10.31083/j.ceog.2021.03.2303myometrial contractionoxytocin receptorpge receptorpgf2α receptoruterotonics
spellingShingle Li-Mei Liao
Jian-Ying Hu
Ting-Ting Wang
Shao-Qiang Huang
Uterine receptor activation in response to uterotonic agents in late-pregnancy rat myometrium following pretreatment with oxytocin: an in vitro study
Clinical and Experimental Obstetrics & Gynecology
myometrial contraction
oxytocin receptor
pge receptor
pgf2α receptor
uterotonics
title Uterine receptor activation in response to uterotonic agents in late-pregnancy rat myometrium following pretreatment with oxytocin: an in vitro study
title_full Uterine receptor activation in response to uterotonic agents in late-pregnancy rat myometrium following pretreatment with oxytocin: an in vitro study
title_fullStr Uterine receptor activation in response to uterotonic agents in late-pregnancy rat myometrium following pretreatment with oxytocin: an in vitro study
title_full_unstemmed Uterine receptor activation in response to uterotonic agents in late-pregnancy rat myometrium following pretreatment with oxytocin: an in vitro study
title_short Uterine receptor activation in response to uterotonic agents in late-pregnancy rat myometrium following pretreatment with oxytocin: an in vitro study
title_sort uterine receptor activation in response to uterotonic agents in late pregnancy rat myometrium following pretreatment with oxytocin an in vitro study
topic myometrial contraction
oxytocin receptor
pge receptor
pgf2α receptor
uterotonics
url https://www.imrpress.com/journal/CEOG/48/3/10.31083/j.ceog.2021.03.2303
work_keys_str_mv AT limeiliao uterinereceptoractivationinresponsetouterotonicagentsinlatepregnancyratmyometriumfollowingpretreatmentwithoxytocinaninvitrostudy
AT jianyinghu uterinereceptoractivationinresponsetouterotonicagentsinlatepregnancyratmyometriumfollowingpretreatmentwithoxytocinaninvitrostudy
AT tingtingwang uterinereceptoractivationinresponsetouterotonicagentsinlatepregnancyratmyometriumfollowingpretreatmentwithoxytocinaninvitrostudy
AT shaoqianghuang uterinereceptoractivationinresponsetouterotonicagentsinlatepregnancyratmyometriumfollowingpretreatmentwithoxytocinaninvitrostudy