230: Antenatal maternal hypoxic stress: adaptations of the placental renin-angiotensin system

OBJECTIVE: Antenatal Maternal Hypoxia (AMH) can result in pathophysiologic changes in both mother and fetus including alterations in placental morphology and gene regulation. We previously reported alterations in placental renin-angiotensin system (RAS) genes in a small animal model of placental insufficiency. The objective of this study was to test the hypothesis that antenatal maternal hypoxic stress in pregnant mice leads to alterations in the placental RAS similar to those observed with placental insufficiency. STUDY DESIGN: Pregnant FVB/NJ mice dams were exposed to 10.5% O2 for 48 hours, from 15.5 to 17.5 day post coitum (n=5) and compared to controls (n=5). mRNA and protein expression of several RAS genes in the placenta were measured. p < 0.05 was considered significant. RESULT(S): 1) Placental angiotensinogen (AGT) mRNA was undetectable in both groups; however, AGT protein expression was present and increased significantly with AMH compared to controls. 2) In AMH, although ReninmRNAlevels were reduced, protein expression was increased in association with increased miRNA 199b, (yielding increased renin translation). 3) In AMH, placental angiotensin converting enzyme (ACE)-1 mRNA was unaltered; however, protein expression increased significantly, in association with decreased miRNA 27a (yielding increased ACE-1 translation). 4) In AMH placenta, ACE-2 mRNA was significantly reduced, whereas protein expression was significantly greater, in association with reduced miRNA 429. 5) In AMH placenta, angiotensin II type (AT)-1a receptor mRNA expression was unaltered and AT-1a receptor protein expression was unchanged; AT-2 receptor mRNA and proteins were undetectable in both groups. CONCLUSION(S): In the normal murine placenta, several components of RAS are present, and in response to AMH, several of these elements undergo important changes. In addition, differential expression of RAS mRNA and proteins indicate post-transcriptional regulatory mechanisms involved with hypoxic stress and warrant further investigation.