Lifetime consequences of abnormal fetal pancreatic development.
There is ample evidence that an adverse intrauterine environment has harmful consequences for health in later life. Maternal diabetes and experimentally induced hyperglycaemia result in asymmetric overgrowth, which is associated with an increased insulin secretion and hyperplasia of the insulin-producing B-cells in the fetuses. In adult life, a reduced insulin secretion is found. In contrast, intrauterine growth restriction is associated with low insulin secretion and a delayed development of the insulin-producing B-cells. These perinatal alterations may induce a deficient adaptation of the endocrine pancreas and insulin resistance in later life. Intrauterine growth restriction in human pregnancy is mainly due to a reduced uteroplacental blood flow or to maternal undernutrition or malnutrition. However, intrauterine growth restriction can be present in severe diabetes complicated by vasculopathy and nephropathy. In animal models, intrauterine growth retardation can be obtained through pharmacological (streptozotocin), dietary (semi-starvation, low protein diet) or surgical (intrauterine artery ligation) manipulation of the maternal animal. The endocrine pancreas and more specifically the insulin-producing B-cells play an important role in the adaptation to an adverse intrauterine milieu and the consequences in later life. The long-term consequences of an unfavourable intrauterine environment are of major importance worldwide. Concerted efforts are needed to explore how these long-term effects can be prevented. This review will consist of two parts. In the first part, we discuss the long-term consequences in relation to the development of the fetal endocrine pancreas and fetal growth in the human; in the second part, we focus on animal models with disturbed fetal and pancreatic development and the consequences for later life.
Holemans
K
K
Department of Obstetrics and Gynaecology, Katholieke Universiteit Leuven, UZ Gasthuisberg, Herestraat, 49, 3000 Leuven, Belgium. kathleen.holemans@uz.kuleuven.ac.be
Aerts
L
L
Van Assche
F A
FA
D000818:Animals; D031204:Caloric Restriction; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007515:Islets of Langerhans / Q000002:abnormalities* / Q000378:metabolism / Q000503:physiopathology*; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena / Q000502:physiology*; D011502:Protein-Energy Malnutrition / Q000378:metabolism / Q000503:physiopathology