The mRNA expression of prostaglandin E receptors EP2 and EP4 and the changes in glycosaminoglycans in the sheep cervix during the estrous cycle

Transcervical artificial insemination in sheep is limited by the inability to completely penetrate the cervix with an inseminating pipette. Penetration is partially enhanced at estrus due to a degree of cervical relaxation, which is probably regulated by cervical prostaglandin synthesis and extracellular matrix remodeling. Prostaglandin E2 acts via prostaglandin E receptors EP1 to EP4, and EP2 and EP4 stimulate smooth muscle relaxation and glycosaminoglycan synthesis. This study investigated the expression of EP2 and EP4 mRNA and glycosaminoglycans in the sheep cervix during the estrous cycle. Sheep cervices were collected prior to, during, and after the luteinizing hormone (LH) surge and during the luteal phase. The mRNA expression of EP2 and EP4 was determined by in situ hybridization, glycosaminoglycan composition was assessed by Alcian blue staining, and hyaluronan concentration was investigated by ELISA. The expression of EP2 mRNA was greatest prior to the LH surge (P = 0.02), although EP2 and EP4 were expressed throughout the estrous cycle. Hyaluronan was the predominant glycosaminoglycan, and hyaluronan content increased prior to the LH surge (P < 0.05). Cervical EP2 mRNA expression changed throughout the estrous cycle and was greatest prior to the LH surge. We propose that prostaglandin E2 binds to EP2 and EP4 stimulating hyaluronan synthesis, which may cause remodeling of the cervical extracellular matrix, culminating in cervical relaxation.