title: Detection of expressional changes induced by intrauterine growth restriction in the developing rat pancreas.
abstract: Intrauterine growth retardation (IUGR) is a disorder that can result in permanent changes in the physiology and metabolism of the newborn, which increased the risk of disease in adulthood. Evidence supports IUGR as a risk factor for the development of diabetes mellitus, which could reflect changes in pancreas developmental pathways. We sought to characterize the IUGR-induced alterations of the complex pathways of pancreas development in a rat model of IUGR. We analyzed the pancreases of Sprague Dawley rats after inducing IUGR by feeding a maternal low calorie diet from gestational day 1 until term. IUGR altered the pancreatic structure, islet areas, and islet quantities and resulted in abnormal morphological changes during pancreatic development, as determined by HE staining and light microscopy. We identified multiple differentially expressed genes in the pancreas by RT-PCR. The genes of the insulin/FoxO1/Pdx1/MafA signaling pathway were first expressed at embryonic day 14 (E14). The expressions of insulin and MafA increased as the fetus grew while the expressions of FoxO1 and Pdx1 decreased. Compared with the control rats, the expressions of FoxO1, Pdx1, and MafA were lower in the IUGR rats, whereas insulin levels showed no change. Microarray profiling, in combination with quantitative real-time PCR, uncovered a subset of microRNAs that changed in their degree of expression throughout pancreatic development. In conclusion, our data support the hypothesis that IUGR influences the development of the rat pancreas. We also identified new pathways that appear to be programmed by IUGR.
authors.affiliation: Department of Endocrinology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing 210008, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing 210008, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Endocrinology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing 210008, China.
authors.forename: Yuee
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Department of Endocrinology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing 210008, China ziyangz@126.com.
authors.forename: Ziyang
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Endocrinology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing 210008, China qianqil@163.com.
authors.forename: Qianqi
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001835:Body Weight; D031204:Caloric Restriction; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010179:Pancreas / Q000196:embryology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D000071161:Forkhead Box Protein O1
chemical_list: D018398:Homeodomain Proteins; D007328:Insulin; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D015534:Trans-Activators; C094696:Klrg1 protein, rat; C084010:pancreatic and duodenal homeobox 1 protein; C074639:Foxo1 protein, rat; D000071161:Forkhead Box Protein O1
keywords: Intrauterine growth retardation; insulin/Fox-O1/Pdx1/MafA; let-7d*; miR-21*; miR-23a*; microRNA; pancreas development