PSVIII-B-18 Sustained Maternofetal Inflammation at mid-Gestation Causes Intrauterine Growth Restriction of the Sheep Fetus That is Characterized by Poor Muscle Mass and Asymmetric Body Composition Near Term

Abstract Induction of maternofetal inflammation for two wk at 0.7 gestation was previously shown to cause fetal intrauterine growth restriction (IUGR) in sheep. However, the impact of sustained maternofetal inflammation during peak placental development and growth at mid-gestation has not been explored. Therefore, our objective was to determine the effects of sustained maternofetal inflammation during this period on subsequent fetal growth. Pregnant ewes were injected every 3rd day from the 50th to 65th d of gestation (dGA; term=150 dGA) with saline (control; n=10) or bacterial lipopolysaccharide endotoxin to induce maternofetal inflammation and IUGR (MI-IUGR; n=12). Fetuses were surgically catheterized on dGA 118 to collect daily blood samples and necropsied on dGA 125 to assess growth metrics. From dGA 120 to 125, blood O2, CO2, and HCO3 content was less (P < 0.05) for MI-IUGR fetuses than controls, but blood glucose, lactate, and pH did not differ. Circulating granulocytes and platelets were greater (P < 0.05) and red blood cells were less (P < 0.05) for MI-IUGR fetuses than controls, but circulating monocytes, lymphocytes, and total leukocytes did not differ. At necropsy, MI-IUGR fetuses were 23% lighter (P < 0.05), hindlimbs were 25% smaller (P < 0.05), and cannon bones were 6% shorter (P < 0.05) compared to controls. MI-IUGR fetuses also had reduced (P < 0.05) semitendinosus, flexor digitorum superficialis, and longissimus dorsi masses compared to controls. Heart, liver, and brain masses did not differ between control and MI-IUGR fetuses, but brain/bodyweight and heart/bodyweight were greater (P < 0.05) for MI-IUGR fetuses. We conclude that sustained maternofetal inflammation during peak placental development at mid-gestation led to fetal hypoxemia (but not hypoglycemia), which impaired muscle growth and caused asymmetrical body composition near term. This reflects the growth phenotype in other models of IUGR and indicates at least partial placental insufficiency.