Metabolic response of syncytiotrophoblast mitochondria to maternal obesity

s / Placenta 34 (2013) A1–A99 A38 or more consecutive early pregnancy losses. Chi square test and multiple logistic regression models were used for statistical analysis. Results: We identified 36 cases of miscarriage and 1780 controls. Percentage of H.pylori seropositive serum was higher in mothers with a new miscarriage (38,9%) than in mothers with physiological pregnancy (26,5%); however the differencewas not significant. When only primigravidaewere considered (14 miscarriages vs 932 physiological pregnancies) the difference was significant (50,0% vs 23,2% respectively) (p 1⁄4 0.017, after adjustment for maternal age and BMI). In our study population we further identified 25 mothers with a history of RM. Interestingly, only 1 (4,0%) RM women were seropositive for H. pylori. Conclusions:H. pylori infection could increase the risk ofmiscarriage infirst pregnancy, but there is no relation between H.pylori seropositivity and RM. http://dx.doi.org/10.1016/j.placenta.2013.06.112 P1.76. METABOLIC RESPONSE OF SYNCYTIOTROPHOBLAST MITOCHONDRIA TO MATERNAL OBESITY James Mele, Alina Maloyan, Leslie Myatt UTHSCSA, San Antonio, TX, USA Background: In adult tissues the chronic inflammation and oxidative stress of obesity is associated with mitochondrial dysfunction. Inflammation and oxidative stress are found in the placenta with increasing maternal adiposity but the effect on mitochondrial energetics and metabolism is unknown. Objective: We tested the hypothesis that metabolic flexibility of syncytiotrophoblast is altered in placentas from women of increased adiposity. Methods: Cytotrophoblasts isolated from placentae collected by c-section at term (no labor) fromwomen (n1⁄433) of BMI range 18-45 were allowed to syncytialize (ST) for 72hr. Mitochondrial functionwas assessed using a XF24 analyzer (Seahorse Bioscience). In separate experiments (n1⁄44 each with ST from lean [LN], overweight [OW] or obese [OB] women) media contained either galactose (10mM) or glucose (17mM) for the final 24hr prior to analysis. In galactose, ST must rely exclusively on mitochondrial respiration for energy. Basal oxygen consumption rate, ATP coupled and maximum respiration; spare capacity, proton leak, nonmitochondrial respiration and coupling efficiency were calculated using ETC inhibitors oligomycin (0.5mM), FCCP (0.75mM) and rotenone (3mM)/antimycin A (1.5mM). Results: Basal, ATP-coupled and maximal respiration and spare capacity of ST decreased significantly (p<0.05, ANOVA) with increasing maternal adiposity. When challenged with galactose, ST from LN women were able to significantly increase basal and ATP-coupled respiration (p1⁄40.01) but with no change in maximal respiration and hence a significant decrease in spare capacity (p1⁄40.02). However there was no response to galactose challenge in respiratory parameters in ST of OW or OB women Conclusions: Mitochondrial dysfunction is evident in ST with increasing maternal adiposity. ST from lean women are metabolically flexible as they can respond tometabolic challenge by increasingoxidative phosphorylation. This response is lost in OWor OBwomen. In vivo this may result in placental and fetal compromise in the obesemotherwhen facedwith further stressors. http://dx.doi.org/10.1016/j.placenta.2013.06.113 P1.77. SEXUAL DIMORPHISM IN THE EFFECT OF MATERNAL ADIPOSITY ON PLACENTAL MIR-210 EXPRESSION Sribalasubashini Muralimanoharan, Chunming Guo, Leslie Myatt, Alina Maloyan UTHSCSA, San antonio, USA Obesity in pregnancy, which leads to developmental programming, is associated with oxidative stress and mitochondrial dysfunction in the placenta. MicroRNAs (miRs) regulate various physiological and pathological events in placenta. We demonstrated increased placental miR-210 with preeclampsia and a causative role for miR-210 in mitochondrial dysfunction in trophoblast. We hypothesized that miR-210 expression is dysregulated in the placenta with increasing maternal adiposity. Placentas of both male and female fetuses were collected from healthy lean (LN: BMI 19-24.9), overweight (OW: BMI 25-29.9) and obese (OB: BMI 30-45) women (n1⁄46 each sex/group) after C-section at term with no labor. Expression of miR-210 and its mitochondrial target genes were analyzed by RT-PCR and Western Blot. No differences in placental miR-210 expressionwere seenwith increasing adiposity inmales. However, in placentas of female fetuses miR-210 expression was upregulated 3-fold in OW and 2fold in OB compared to LN women (p<0.05). Correspondingly miR-210 target genes, Iron Sulfur Cluster assembly proteins, NADH dehydrogenase (ubiquinone) 1a subcomplex 4 and succinate dehydrogenase complex, subunit B, were significantly reduced in female placentas with increasing maternal adiposity (p<0.05). No statistically significant changes in these genes were found in male placentas. No changes in placental HIF-1a, previously shown to regulate miR-210, were detected. Rather, we found a significant increase in NFkB p65 protein expression in both male and female placentas of OW and OB women vs. LN (p<0.05). ChIP analysis confirmed miR-210 expression can be regulated by binding of NFkB p65 to miR-210 promoter. We found a 2-fold increase in p65 binding to the miR210 promoter in female but not male placentas of OW and OB vs. LN women (p<0.05). In summary, we show a sexual dimorphism in placental miR-210 expressionwith increasing maternal adiposity, whichmay at least be partially regulated by the NFkB pathway. Supported by NIH HD075297. http://dx.doi.org/10.1016/j.placenta.2013.06.114 P1.78. GENOME-SCALE ANALYSIS OF THE INFLUENCE OF MATERNAL ADIPOSITY ON THE HUMAN PLACENTAL EPIGENOME Kohzoh Mitsuya , Lu Liu , Jianhua Ruan , Leslie Myatt 1 Center for Pregnancy and Newborn Research, Department of Obstetrics and Gynecology, University of Texas Health Science Center at San Antonio, Texas, USA; Department of Computer Science, University of Texas at San Antonio,