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.

总结： 宫内生长受限（IUGR）影响7-9%的妊娠。它与早产有关 分娩、死产和多种新生儿疾病，包括神经功能障碍， 低血糖和呼吸窘迫即使是成年后，患有IUGR的婴儿也会减少 瘦体重和易患代谢性疾病初步数据显示，在小鼠模型中， 肌肉生长抑制素减少的母亲所生的胎儿比基因型匹配的胎儿长得更大 天生就是控制欲强的母亲此外，作为成年人，他们有更大的肌肉和骨骼 生物力学强度本项目的目标是阐明这一机制， 效果最重要的假设是，肌肉生长抑制素抑制营养输送到生长的 通过减少胎盘营养物质的运输和结构限制的效率， 母胎界面，从而限制胎儿肌肉骨骼生长。为了验证这一点，胎盘 葡萄糖和氨基酸转运，母胎代谢组学将比较 肌肉生长抑制素减少的母鼠和对照母鼠。第二，将在肌肉生长抑制素中检查胎盘组织学。 缺乏肌生长抑制素的母鼠，以确定肌生长抑制素减少是否刺激滋养层侵袭， 母胎血腔发育。项目的成功完成将展示如何 母体肌肉生长抑制素减少可促进胎盘效率和胎儿生长。