163: fetal gender-specific placental “endocannabinoidome” in maternal obesity
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Poster Session I Ultrasound, Fetus, Genetics www.AJOG.org
We recently found that human trophoblast nanovesicles (exosomes)contain C19MC miRNAs, which can deliver C19MC miRNAs tonon-placental recipient cells and attenuate viral infection (PNAS2013). Here we hypothesized that C19MC miRNAs constitute anovel maternal-fetal signaling system.STUDY DESIGN: RNAseq, microarrays and qPCR were used toquantify miRNA expression in triads of placenta and maternal-fetalplasma, obtained at delivery of term healthy women (n¼30). Ul-tracentrifugation and fractionation, verified by nanoparticle trackingdevice, were used to analyze exosomes from primary human tro-phoblasts. To analyze miRNA trafficking to maternal and fetal tissueswe engineered a transgenic mouse in which we introduced a 160 kbsegment of human genomic DNA containing the C19MC cluster.RESULTS: Placenta-specific miRNA species, such as miR-517-3p,which we demonstrated to have an anti-viral activity, were found inboth the maternal and fetal circulation, exhibiting an extraordinaryspecies correlation (p <2.2e-16). Isolated trophoblastic exosomesalso contain these miRNAs. Our “humanized” C19MC transgenicmouse lines constitutively expressed a low level of C19MC miRNAs.In contrast, during pregnancy C19MC miRNAs were found mainlyin the placenta, and expression was >100-fold higher than in anyother tissue (p<0.0001). Importantly, breeding of wild-type femaleswith C19MC transgenic males confirmed high miRNA expression intransgenic placentas and also revealed the expression of C19MCmiRNAs primarily in the circulation of wild type mothers, as well asin the fetal blood.CONCLUSION: Our data define an unprecedented, non-hormonalsystem of miRNA communication between the placenta and feto-maternal compartments, which may serve to limit the maternal-fetalspread of viruses.
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Fetal gender-specific placental “endocannabinoidome”in maternal obesityNatalia Schlabritz-Loutsevitch1, Jacques Samson1, Sonali Gupta1,Mauro Schenone1, Brian Brocato1, Danielle Tate1, Raisa Krutilina1,Cezary Skobowiat2, Andrzej Slominski2, Bob Moore3,Giancarlo Mari11University of Tennessee Health Science Center, Obstetrics and Gynecology,Memphis, TN, 2University of Tennessee Health Science Center, Pathology,Memphis, TN, 3University of Tennessee Health Science Center,Pharmacology, Memphis, TNOBJECTIVE: Endocannabinoids (ECBs) represent a group of lipidsignaling molecules, derived from polyunsaturated fatty acids. ECBsregulation is critical for embryo development and pregnancymaintenance. Dysregulation of peripheral ECBs is a hallmark ofobesity. We previously reported the changes in placental “endo-cannabinoidome” in obese non-human primates (Brocato et al.,2013). There are no data available regarding placental ECBs systemin maternal obesity (MO) in human pregnancy. In light of theepidemic proportion of MO, these data are urgently needed. Thegoal of this study was to evaluate the expression of key enzymes andreceptors of ECBs in placentas of the male fetuses, exposed to MO.STUDY DESIGN: Four non-obese and three obese patients withoutpregnancy-related complications and diabetes were included intothis study based on their pre-pregnancy BMI (24.1 �2 kg/m2 and39.1 �7 kg/m2). Placentas were collected at the time of cesareandelivery at term. The Western Blot analyses and immunohisto-chemistry were performed with the commercially available anti-bodies. Data were analyzed using two tailed Student’s t-test,
S94 American Journal of Obstetrics & Gynecology Supplement to JANUARY 2
significance was set at p<0.05. The study was approved by theinstitutional review board (10-01129-XP).RESULTS: The expressions of ECBs receptors: CB1 and CB2 andN-arachidonoyl-phosphatidylethanolamine, cleaved by phospholi-pase D (NAPE-PLD) were significantly decreased in MO (Fig.1).The expressions of fatty acid amide hydrolase (FAAH) andmonoacyl glycerol lipase (MAGL) were not different between twogroups.CONCLUSION: The decreased expression of NAPE PLD-the enzyme,involved in the synthesis of ECBs ligand- anandamide (AEA), mightresult in the decreased AEA concentrations, as documented inthe adipose tissue from obese subjects and pregnant non-human primates (Brocato et al., 2013). Taking in considerationthe reported inhibitory role of AEA on the myometrial contractionand down regulation of placental CB1 receptors in labor, ourdata might hold the key to the mechanisms, leading to pretermdeliveries in MO.
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Midtrimester isolated polyhydramnios in monochorionicdiamniotic multiple gestationsAndrew Chon1, Lisa Korst2, Arlyn Llanes2, David Miller2,Joseph Ouzounian2, Ramen Chmait21Kaiser Permanente Los Angeles, Department of Obstetrics and Gynecology,Los Angeles, CA, 2Keck School of Medicine, University of SouthernCalifornia, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Los Angeles, CAOBJECTIVE: The natural history of monochorionic diamniotic mul-tiple gestations complicated by midtrimester isolated poly-hydramnios (iPoly), in which one amniotic sac has polyhydramniosbut the other has normal amniotic volume, remains unclear. Theobjective of this study was to identify risk factors for development ofovert twin-twin transfusion syndrome (TTTS) in patients diagnosedwith midtrimester iPoly.STUDY DESIGN: Patients referred for possible TTTS between 16 and26 weeks’ gestation were studied (2006-2013). The diagnosis of iPolywas established if the maximum vertical pocket of amniotic fluidmeasured �8 cm in the recipient’s sac and >2 cm in the donor’s sacat the consultative ultrasound.RESULTS: Of 628 consecutive patients referred for possible TTTS,11.8% (74) were diagnosed with iPoly; 1 remained undelivered.The overall perinatal survival of at-least-one twin in the 73 iPoly
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