206: Melanocortin binding activity in term and preterm human placenta

term and preterm human placenta J. Newton, Minying Cai, Hua Xu, Kathryn Reed University of Arizona, Obstetrics and Gynecology, Tucson, AZ, University of Arizona, Chemistry, Tucson, AZ, University of Arizona, Pediatrics, Tucson, AZ OBJECTIVE: The purposes of this study were to compare melanocortin binding activity and melanocortin receptor subtype expression in human placenta samples collected in four clinical settings: preterm notin-labor, preterm labor, term not-in-labor, and term labor. STUDY DESIGN: Following IRB approval, placenta samples were collected at delivery in each of the four clinical settings listed above. Melanocortin binding activity using 125I-NDP-MSH was determined with 1 mg of total membrane protein from each sample. Competition binding assays between the non-selective 125I-NDP-MSH and -MSH analogs that have highly specific receptor subtype agonist activity were used to identify receptor subtype activity. Lastly, 500 ng of total placental RNA was used as original template for quantitative RT-PCR using validated TaqMan probes for melanocortin receptors 1 and 3 (MC1R and MC3R). Average MSH binding activities were compared between groups using two-tailed Students t-test. Relative expression of MC1R and MC3R were compared using the Pfaffl method. RESULTS: Human placenta samples express MSH-binding activity. This activity is significantly higher in the setting of labor compared to not-in-labor, both at term and preterm. Competition binding assays with highly selective receptor agonists showed that MC3R is the predominant melanocortin receptor in human placenta. In the quantitative RT-PCR studies, both MC1R and MC3R are detected at varying expression levels. While MC1R was expressed at a relatively constant level in this sample set, MC3R expression levels were significantly higher in term labor samples compared to preterm not-in-labor samples. CONCLUSION: Melanocortin receptors, which have important physiologic functions including roles in energy homeostasis and inflammation, are expressed in human placenta. The key melanocortin receptor in placental MSH binding activity appears to be the MC3R subtype based on both the RT-PCR and competitive binding assays. Finally, the level of melanocortin binding activity and MC3R gene expression varies with gestational age and in the setting of term and preterm labor. 207 Role of foramen ovale in the regulation of fetal cardiac output: a fetal sheep study with acute ductus arteriosus occlusion Jason Hashima, David Sahn, Muhammad Ashraf, Vanessa Rogers, Stephen Langley, Lowell Davis, Roger Hohimer, Juha Rasanen Oregon Health and Science University, Obstetrics and Gynecology, Portland, OR, Oregon Health and Science University, Pediatric Cardiology, Portland, OR, Oregon Health and Science University, Pediatric Surgery, Portland, OR, Oregon Health & Science University, Maternal Fetal Medicine, Portland, OR OBJECTIVE: We hypothesized that during acute fetal ductus arteriosus (DA) occlusion (DO) foramen ovale (FO) volume blood flow increases, in order to maintain adequate systemic cardiac output. STUDY DESIGN: Nine ewes with singleton pregnancies underwent surgery at 120-126 gestational days (term 145 days) for the placement of a vascular occluder around fetal DA. Fetal carotid artery and jugular vein were cannulated. After a 5-day recovery, fetal heart rate (FHR), right (RVCO) and left (LVCO) ventricular cardiac outputs were measured by ultrasonography. Pulmonary (Qp) and foramen ovale (Qfo) volume blood flows, and systemic CO (combined cardiac output-Qp) were calculated at baseline, 15 and 60 minutes after DO, and 15 minutes after release of DO. Fetal mean arterial (mABP) and central venous (CVP) pressures, and pO2 and oxygen saturation were monitored. RESULTS: All the data are presented as means (SD). * p 0.05, compared with baseline. CONCLUSION: Acute DO in fetal sheep leads to decreased RVCO and increased LVCO, however systemic CO decreases. The rise in LVCO is caused by increased Qp with no change in the Qfo. Fetal CVP increases and arterial oxygen saturation decreases during DO. These findings suggest that fetal foramen ovale has a limited capacity to increase its volume blood flow, at least in response to acutely increased right ventricular afterload. Poster Session I Clinical Obstetrics, Medical-Surgical-Disease, Neonatology, Physiology-Endocrinology www.AJOG.org