304 SPO Abstracts

43 DIETARY POlYlllSAlUIATED FATTY ACID (PUFA) PREVENTS IlALFORIIATlIJIS IN OFFSPRIIIG OF DIARETIC RATS_ Reece EA, I/u YIC, Borenstein M, Aksoy N, Sloskey G, Depts_ of DB/GYN, Pulmonary Medicine, School of Pharmacy, T"""le Univ. School of Medicine, Philadelphia, PA. OBJECTIVE: Altered metabol ic fuels IIIIIOIlg poorly controlled diabetics is associated with an increased malformation rate. Conversely, recent studies have demonstrated that preconception glycemic control results in a decreased rate of mal formations. However, Meticulous family plaming is necessary in order to effect this benefit. We have reported previously, that arachi' donic acid (M) supplementation to hyperglycemic culture media, in which ..mryos were grown during organogenesis, significantly reduces the mal formation rate. In the current experiments we used a dietary source of M which could serve as a pharmacologic prophylaxis to obviate the teratogenic effects of hyperglycemia. S1U)Y DESIGN: SO-day-old Sprague-Dawley rats were II18ted, and following conception, 65 ~/kg of streptozocin was injected intravenously on pregnancy day 6 to induce experimental diabetes and allowed glucose levels to remain above 350 ~/dl (normal = 150 ~/dl). Rats were fed a normal diet, and via medicine dropper 0.5 ml of safflower oil or primrose oil (PUFA and a source of M) was adninistered orally twice daily. Maternal blood was obtained from rats during organogenesis for biochemical analysis. On pregnancy day 12, rats were sacrificed and ..mryos and yolk sacs were explanted, examined morphologically and biochemically. RESlA.TS: Using safflower oil, the incidence of neural tube defects was significantly reduced from 21.9% to 6.2X (p <0.001), while primrose oil was associated with e reduction from 21.9% to 15. IX (p >0.05). The M level was shown to increase by almost two-folds with safflower oil (0.76 to 6.12), but was only marginally increased with primrose oil (0.17 to 0.55). Additional studies are in progress: Assays for prostaglandins, their metabol ites and myoinositol and IIIOrphologic studies. CXIICLUSIIJIS: These data confirm our previous findings that diabetic ..mryopathy is associated with a deficiency state in essential fatty acid. Furthermore, the use of a dietary PUFA which specifically increases M levels. may serve as a pharo macolosic prophylaxis against diabetes' induced consenital mal formations.

January 1993 Am J Obstet Gynecol

44 KETOACIDS ATTENUATE Z.('H]DEOXYGLUCOSE UPTAKE IN HUMAN TROPHOBLASTS ISOLA TED FROM FIRST TRIMESTER CHORIONIC VILLI. P. Shubert", M.B. Landon, S.G. Gabbe, and D.A. Knissx, Department of Obstetrics & Gynecology (Division ofMaternal·FelalMedicine). The Ohio State University College of Medicine. Columbus. Ohio. OBJECTIVE: This study tested the hypothesis that ketoacids (acetoacetic acid and I\-hydroxybutyrate) may alter uptake of nutrients by the placenta and, thereby, contribute to compromised availability offetal fuels. Glucose uptake was examined in an in vitro model of first trimester human trophoblasts.

STUDY DESIGN: Trophoblasts were grown in monolayer culture as established cell lines after isolation from chorionic villi by CVS for genetic assessment of the fetus. The cells were grown for 2 days in FI2IDMEM+15% fetal bovine serum before initiation of experiments. For glucose uptake experiments, the cells were grown overnight in serum-free medium, rinsed with glucose-free HEPES­buffered saline and incubated for I hr at 37°C with acetoacetic acid (5 mmol/L), after which 2-('H]deoxyglucose (2.['H]DG) uptake was measured by incubating cells with 2.['H]DG (0.1 mmol/L) for 5 min at 37°C. After rinsing the cells, they were solubilized· with NaOH and radioactivity was measured by liquid scintillation spectrometry. The effect of ketoacids on basal and stimulated 2-[lH]DG uptake was measured by incubating cells with acetoacetic acid in the presence or absence of insulin·like growth factor-I (lGF·I, 100 ng/mL). RESUL TS: When cells were incubated with 5 mmol/L acetoacetate (24 hrs) followed by a 60·min incubation in the presence or absence of 100 ng/mL IGF·I, there was a decrease in both basal and IGF·I·stimulated 2·('HJDG uptake (46% decrease vs. basal~ 59% decrease vs. IGF-I-stimulated uptake). Similar findings were noted after a I-hr incubation with acetoacetate (46% decrease vs. basal; 61% decrease vs. IGF-stimulated uptake). CONCLUSIONS: These data indicate that ketoacids can attenuate both basal and IGF·I·stimulated 2.('H]DG uptake in placental trophoblast·like cells isolated from first trimester chorionic villi. This trophoblast cell culture system may serve as a useful model system for studies of the mechanism of altered glucose utilization in response to ketosis and may provide information on the role of placental glucose transport in diabetic ketoacidosis.