Date of Award
2009
Degree Type
Thesis
Degree Name
Master of Science
Program
Physiology and Pharmacology
Supervisor
Dr. Thomas Kennedy
Second Advisor
Dr. Stephen Sims
Third Advisor
Dr. Timothy Régnault
Abstract
Inhibition of prostaglandin (PG) production renders the sensitized rat endometrium unresponsive to an implanting blastocyst or an artificial stimulus. Responsiveness can however be restored by the co-administration of PGE2, which binds to the four E prostanoid (EP) receptors; EP1, EP2, EP3, or EP4. Furthermore, the EP2 and EP4 receptors stimulate the production of cAMP, suggested to be important in artificially induced decidualization. To investigate PGE2 function, this study looked at the role of the EP2, EP3, and EP4 receptors and cAMP degrading phosphodiesterase (PDE) enzymes in endometrial sensitization and artificially induced stimulation. The EP4 receptor has significantly (p<0.05) greater protein levels in the maximally sensitized endometrium compared to endometria sensitized with low estrogen (Day 5L). Immunolocalization studies showed that the EP2, EP3, and EP4 receptors were differentially present in the luminal and glandular epithelium and co-localized with the PDE enzymes. The role of the individual receptors in artificially induced decidualization was investigated using specific agonists. Agonists for all three receptors resulted in uterine endometrial vascular permeability (EVP) and decidualization that were significantly (p<0.05) greater than vehicle treated animals. However, L09-2688 (EP4 agonist) showed the greatest effects and was not significantly different from PGE2 using either endpoint. Total PDE activity levels were found to be significantly (p<0.05) reduced in the maximally sensitized endometrium compared to Day 5L endometria. The effect of PDE inhibition on artificially induced decidualization was then determined in Day 5L animals. Compared to vehicle, PDE4 inhibition resulted in significantly (p<0.05) greater EVP, while PDE7B inhibition did not. In contrast, both inhibitors resulted in significantly (p<0.05) increased decidualization compared to vehicle treated animals. Collectively these results indicate that EP4 receptor stimulation and PDE4 enzyme inhibition have the greatest effects on EVP and decidualization following an artificial deciduogenic stimulus.
Recommended Citation
Mather, James Patrick, "Phosphodiesterases and E Prostanoid Receptors in Endometrial Sensitization and Artificially Induced Decidualization" (2009). Digitized Theses. 4240.
https://ir.lib.uwo.ca/digitizedtheses/4240