Effect of Maternal Myostatin on Placental Support of Fetal Growth

母体肌生长抑制素对胎盘支持胎儿生长的影响

• 批准号: 10183279
• 负责人: Laura Clamon SCHULZ
• 金额: $ 18.43万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-05 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10183279
• 关键词: Activins; Address; Adult; Adult Children; Affect; Age; Amino Acids; Area; Biomechanics; Birth; Blood Circulation; Blood flow; Cells; Cultured Cells; Data; Development; Embryo; Environment; Excision; Failure; Family; Family member; Fetal Growth; Fetal Growth Retardation; Fetus; GDF8 gene; Genetic; Genotype; Glucose; Glycine; Goals; Growth; Growth Factor; Health; Histology; Human; Hypoglycemia; Impairment; In Vitro; Infant; Insulin Resistance; Isoleucine; Knock-out; Leucine; Ligands; Link; Maternal-Fetal Exchange; Mediating; Metabolic Diseases; Mothers; Mus; Muscle; Musculoskeletal; Neurologic; Nodal; Nutrient; Operative Surgical Procedures; Pathologic; Pharmacology; Placenta; Placental Insufficiency; Placentation; Pregnancy; Pregnant Women; Premature Birth; Respiratory distress; Signal Transduction; Structure; Surface; System; Tensile Strength; Testing; Therapeutic; Thinness; Tissues; Uterus; Wild Type Mouse; bone; bone mass; fetal; fetal blood; glucose transport; improved; in vivo; maternal serum; member; metabolomics; mouse model; neonatal morbidity; novel therapeutics; obesity risk; offspring; receptor; recombinase-mediated cassette exchange; stillbirth; trophoblast

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.

概括： 宫内生长限制（IUGR）会影响7-9％的怀孕。它与早产相关 出生，静止出生和多种新生儿病毒，包括神经系统障碍， 低血糖和呼吸窘迫。即使成年人，患有IUGR的婴儿也减少了 瘦质量和代谢疾病的倾向。初步数据显示，在鼠标模型中 肌抑制素降低的母亲出生的胎儿比基因型匹配的胎儿大得多 天生是为了控制母亲。此外，作为成年人，它们具有更大的肌肉和更大的骨头 生物力学强度。当前项目的目的是阐明此机制 影响。总体假设是，肌抑制素抑制了营养递送到生长 胎儿通过减少胎盘养分的运输和结构限制胎儿的效率 孕产妇界面，从而限制胎儿肌肉骨骼生长。为了测试这一点，胎盘 将比较葡萄糖和氨基酸的转运，以及孕产妇代谢组学 肌抑素减少和控制大坝。其次，将在肌抑素中检查胎盘组织学 缺乏大坝以确定肌生抑素的减少是否刺激滋养细胞的侵袭和 产妇血液空间的发展。成功完成项目将显示如何 孕产妇肌抑制素的减少可以促进胎盘效率和胎儿生长。