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Published on: January 6, 2023
Distribution and Function of Prostaglandin E2 Receptors in Mouse Uterus: Translational Value for Human Reproduction
Deborah P Fischer1, Anna L Griffiths2, Sylvia Lui2
1Division of Pharmacy and Optometry, School of Health Sciences (D.P.F., K.M.M.) and Division of Developmental Biology and Medicine, School of Medical Sciences (S.L.), Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom; School of Pharmacy, University of Bradford, Bradford, West Yorkshire, United Kingdom (A.L.G., U.J.S.); Bradford Institute for Health Research, Bradford Royal Infirmary, Duckworth Lane, Bradford, West Yorkshire, United Kingdom (D.F.); Obstetrics and Gynaecological Oncology, Yorkshire Clinic, Bradford Road, Bingley, West Yorkshire, United Kingdom (P.J.D.); Department of Bioengineering, Imperial College London, London, United Kingdom (D.F.W.); and JeniVision Inc., Irvine, California, USA (D.F.W.). debbie.fischer@manchester.ac.uk.
Selective E-type prostanoid (EP) receptor agonists show promise for managing uterine conditions. Targeting EP3 receptors in nonpregnant mice offers a valid preclinical model for developing new drugs to prevent uterine hypercontractility.
Area of Science:
- Reproductive biology
- Pharmacology
- Gynecology
Background:
- Prostaglandin E (PGE) analogs are clinically used for cervical ripening and labor induction.
- Selective EP receptor agonists may offer improved induction or management of uterine hypercontractility in conditions like dysmenorrhea and preterm labor.
Purpose of the Study:
- To investigate the functional E-type prostanoid (EP) receptor population in isolated human and mouse uteri.
- To evaluate the therapeutic potential of selective EP receptor agonists for uterine conditions.
- To validate the use of mouse models for preclinical drug discovery.
Main Methods:
- Uterine samples were obtained from nonpregnant and pregnant/laboring mice, and from women undergoing hysterectomy or Cesarean section.
- Superfusion and immersion techniques were used to assess vehicle and agonist effects.
- Selective EP2, EP3/1, and EP4 receptor agonists were administered.
Main Results:
- PGE2 evoked excitatory responses in mouse uteri and relaxation in human uteri.
- Selective EP4 agonists inhibited tissue activity in both species.
- EP2 and EP3/1 agonists attenuated uterine contractions, with EP3 showing more pronounced effects, correlating with high EP3 receptor expression.
Conclusions:
- Nonpregnant mouse uteri serve as a valid preclinical model for EP receptor drug discovery.
- EP3 receptors represent a valuable translational drug target for preventing uterine hypercontractility.
- Pharmacological agents targeting EP3 receptors have significant translational value for term pregnancy and labor management.
