Changes in Placental CRH, Urocortins, and CRH-Receptor mRNA Expression Associated with Preterm Delivery and Chorioamnionitis

Abstract

The pathogenesis of preterm delivery (PTD) is not clear, although inflammation/infection play a major role. Corticotropin releasing-hormone (CRH) and Urocortins (Ucns) are involved in the pathophysiology of PTD. This study evaluates trophoblast mRNA expression of CRH, Ucn, Ucn2, Ucn3, and their receptors [CRH-type 1 receptor (CRH-R1), CRH-R2] in infective conditions. To determine whether infection or glucocorticoids contribute to change their placental mRNA expression, the effects of lipopolysaccharide or dexamethasone was evaluated. Placentas were obtained from spontaneous PTD; premature rupture of membranes (pPROM) and pPROM with chorioamnionitis. Placental specimens were collected from women receiving perinatal care at our Division of Obstetrics and Gynecology. Pregnant women delivered preterm were enrolled. mRNA expression was evaluated by RT-PCR. Because CRH and Ucns are involved in immunological functions we evaluated their involvement in PTD with or without infection. CRH, Ucn2, and CRH-R1 mRNA expression were higher, while Ucn and CRHR-2 were lower in pPROM with chorioamnionitis than in PTD and pPROM. Ucn3 mRNA expression was lower in pPROM with and without chorioamnionitis than in PTD. The addition of lipopolysaccharide in trophoblast explants decreased Ucn, Ucn3, and CRH-R2 and increased CRH, Ucn2, and CRH-R1 mRNA expression in a dose-dependent manner. Dexamethasone increased CRH and decreased Ucn2 mRNA expression in a dose dependent manner. Our findings showed a significant impact of pPROM with chorioamnionitis on placental CRH peptides and receptors, suggesting that placental expression of stress-related pathways is activated in infective process.