Effect of Maternal Myostatin on Placental Support of Fetal Growth

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Summary: Intrauterine growth restriction (IUGR) affects 7-9% of pregnancies. It is associated with preterm birth, still birth and multiple neonatal morbidities including neurological impairments, hypoglycemia, and respiratory distress. Even as adults, infants born with IUGR have reduced lean mass, and a propensity to metabolic disease. Preliminary data show that, in a mouse model, fetuses born to mothers with reduced myostatin grow larger than genotype-matched fetuses born to control mothers. Furthermore, as adults, they have larger muscles and greater bone biomechanical strength. The goal of the current project is to elucidate the mechanism of this effect. The overarching hypothesis is that myostatin inhibits nutrient delivery to the growing fetus by reducing placental nutrient transport and structurally limiting the efficiency of the maternal-fetal interface, thereby restricting fetal musculoskeletal growth. To test this, placental glucose and amino acid transport, and maternal-fetal metabolomics will be compared between myostatin-reduced and control dams. Second, placental histology will be examined in myostatin deficient dams to determine whether myostatin reduction stimulates trophoblast invasion and maternal-fetal blood space development. Successful completion of the project will show how maternal myostatin reduction can promote placental efficiency and fetal growth.