Effect of Maternal Myostatin on Placental Support of Fetal Growth

摘要： 胎儿宫内生长受限(IUGR)影响7-9%的妊娠。它与早产有关 分娩、死产和包括神经损伤在内的多个新生儿疾病， 低血糖和呼吸窘迫。即使作为成年人，出生时患有IUGR的婴儿也减少了 体重偏瘦，有代谢性疾病的倾向。初步数据显示，在老鼠模型中， 肌肉生长抑素降低的母亲所生的胎儿比基因匹配的胎儿更大 天生就是用来控制母亲的。此外，作为成年人，他们有更大的肌肉和更大的骨骼 生物力学强度。当前项目的目标是阐明这一现象的机制 效果。最重要的假设是，肌肉生长抑制素抑制营养物质向生长的输送。 通过减少胎盘营养物质的运输和在结构上限制胎盘的效率 母胎界面，从而限制胎儿肌肉骨骼的生长。为了测试这一点，胎盘 葡萄糖和氨基酸转运，以及母婴代谢组学之间的比较 肌肉抑制素-减少和控制大坝。第二，胎盘组织学检查将采用肌肉生长抑素 缺乏确定肌肉生长抑素减少是否刺激滋养层细胞侵袭和 母胎血液空间发育。该项目的成功完成将展示如何 降低母体肌肉生长抑制素可促进胎盘效率和胎儿生长发育。

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.