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

基本信息

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
项目类别：
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

项目摘要

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：宫内生长受限 (IUGR) 影响 7-9% 的妊娠。它与早产有关出生、死产和多种新生儿疾病，包括神经损伤，低血糖和呼吸窘迫。即使成年后，出生时患有 IUGR 的婴儿也减少了瘦体重和代谢疾病的倾向。初步数据表明，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生来就是为了控制母亲。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机制影响。最重要的假设是，肌肉生长抑制素抑制营养物质输送到正在生长的细胞。通过减少胎盘营养物质运输并从结构上限制胎儿的效率母胎界面，从而限制胎儿肌肉骨骼的生长。为了测试这一点，胎盘将比较葡萄糖和氨基酸转运以及母胎代谢组学肌生长抑制素减少和控制的水坝。二、胎盘组织学检查肌生长抑制素缺陷母鼠以确定肌生长抑制素的减少是否会刺激滋养层侵袭和母胎血液空间发育。该项目的成功完成将展示如何母体肌生长抑制素减少可促进胎盘效率和胎儿生长。