Date of Award

2008

Degree Type

Thesis

Degree Name

Master of Science

Program

Physiology and Pharmacology

Supervisor

Tom Kennedy

Second Advisor

Liz Ross

Third Advisor

Gerry Barbe

Abstract

It was recently proposed that prostacyclin (PGI2), acting upon peroxisome proliferator- activated receptor delta (PPARδ), which then heterodimerizes with retinoid-X-receptor alpha (RXRct), initiates decidualization in mice. However, the roles of these nuclear receptors in the early events of decidualization, such as the pre-requisite increase in endometrial vascular permeability (EVP) for the decidual cell reaction, are still unclear. This present study characterized the expressions of the receptors in the artificially stimulated rat endometrium and infused selective ligands for PPARδ and RXRα to elucidate the roles of the receptors during early decidualization in rats. It is hypothesized that PPARδ and RXRα significantly contribute to the early events in decidualization. Endometria from sensitized rats were collected at 2, 4, 8, 16, or 32 hours after deciduogenic stimulation and non-stimulated endometria collected at 0, 8, or 32 hours for PCR, western blot, or immunohistochemistry analyses. No changes in mRNA levels were observed. PPARδ protein levels remained constant at all time points while RXRα levels were highest at 16 hours. PPARδ and RXRα were localized in the glandular and luminal epithelia at all time points. Intraluminal infusions of L165041 (PPARδ agonist) or DHA (RXRα agonist) did not increase EVP or induce appreciable decidualization while PGE2 (EP receptor) infusion markedly increased both parameters. This study proposes that PGE2, presumably acting upon the EP receptors is the main pathway, while PPARδ and RXRα may only play minor roles, in the early events of decidualization.

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