high fat diet induced developmental defects in the mouse oocyte meiotic aneuploidy and fetal growth retardationbrain defects高脂肪饮食诱导小鼠卵母细胞减数分裂发育缺陷非整倍性和胎儿生长retardationbrain缺陷.pdfVIP

High Fat Diet Induced Developmental Defects in the Mouse: Oocyte Meiotic Aneuploidy and Fetal Growth Retardation/Brain Defects 1. 2. 1 1 1 1 Kerri M. Luzzo , Qiang Wang , Scott H. Purcell , Maggie Chi , Patricia T. Jimenez , Natalia Grindler , 3 1 Tim Schedl , Kelle H. Moley * 1 Washington University School of Medicine, Department of Obstetrics and Gynecology, St. Louis, Missouri, United States of America, 2 State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China, 3 Washington University School of Medicine, Department of Genetics, St. Louis, Missouri, United States of America Abstract Background: Maternal obesity is associated with poor outcomes across the reproductive spectrum including infertility, increased time to pregnancy, early pregnancy loss, fetal loss, congenital abnormalities and neonatal conditions. Furthermore, the proportion of reproductive-aged woman that are obese in the population is increasing sharply. From current studies it is not clear if the origin of the reproductive complications is attributable to problems that arise in the oocyte or the uterine environment. Methodology/Principal Findings: We examined the developmental basis of the reproductive phenotypes in obese animals by employing a high fat diet mouse model of obesity. We analyzed very early embryonic and fetal phenotypes, which can be parsed into three abnormal developmental processes that occur in obese mothers. The first is oocyte meiotic aneuploidy that then leads to early embryonic loss. The second is an abnormal process distinct from meiotic aneuploidy that also leads to early e