Endometrial changes induced by prostaglandin E2 and EP4 receptor agonist in albino rats

ABSTRACT

Prostaglandin E2 [PGE2] plays a vital role in the endometrium at the initial phases of pregnancy in laboratory rodents. PGE2 exerts its effects by coupling to four subtypes of receptors designated as EP1, EP2, EP3, and EP4. Recently, a substance that acts specifically on the EP4 receptor was developed [EP4 receptor agonist=EP4A, APS-999 Na]. Endometrial stromal collagen I, total glycosaminoglycans, hyaluronic acid, and CD44 molecule are commonly subjected to drastic changes at the implantation window. This study was conducted to investigate changes in the expression of these components after administration of PGE2 and the EP4A in rat. Immature female albino rats were injected once with normal saline, 50microg of PGE2, of 50microg of EP4A and killed 24 h later. Light microscopy and immunohistochemistry were used in this study. The study results revealed fraying and disintegration of stromal collagen I; accumulation of matrix glycosaminoglycans and hyaluronic acid after PGE2 as well as EP4A injections compared with the control. In addition, EP4A and PGE2 induced the expression of the molecule CD44 on the endometrial luminal and glandular epithelia Edema of the endometrial stroma was obtained after PGE2 and EP4A treatments. This study revealed that PGE2 and EP4A enhanced endometrial factors that are essential for the success of the implantation process. As long as EP4A produced similar effects to PGE2, it could be concluded that PGE2 mediated these actions partially through the EP4 receptor. PGE2 and EP4A may prove to be promising tools for implantation disorders in the clinical field