title: Pathophysiology, cellular and molecular mechanisms of foetal growth retardation.
abstract: In mammals, size at birth is the outcome of length of gestation and rate of foetal growth. In the absence of premature delivery, foetal size within species is determined principally by foetal growth rate which is dependent on both genetic and epigenetic factors. Failure of either of these mechanisms leads to foetal growth retardation. In mammals, including human infants, foetal growth retardation can occur naturally or pathologically. One major cause for natural foetal growth retardation or runting is the increase in litter size. In many cases, however, the cause of runting is unknown. Parental genotype or antigenic differences between the mother and the developing conceptus may be potential causes. Pathological foetal growth retardation or intrauterine growth retardation (IUGR) is due to genetic causes (chromosomal abnormalities or inherited syndromes) or epigenetic causes (intrauterine infections, toxins and chemicals, maternal diseases of pregnancy affecting the placenta). The underlying pathophysiological processes that occur at the cellular and molecular level in IUGR are still unknown. Reduction in the supply of substrates that are necessary for normal cellular function, and alteration in mediator molecules that regulate cellular growth and differentiation, are important mechanisms. A decrease in growth promoting factors or an increase in growth inhibitory factors may lead to growth failure. Growth factors and their receptors are expressed in the developing embryo (as early as the 1-2-cell stage), placenta and maternal uterine tissues, suggesting that these molecules may play a role in regulating normal growth and differentiation of the conceptus as well as maternal reproductive tissues. The local expression within developing tissues indicates that these factors act in either autocrine or paracrine mechanism. Recent studies using gene targeting to knock out one allele of insulin-like growth factor II (IGF II) gene in mice which resulted in growth retarded pups at birth, strongly support the importance of local IGF II in regulating tissue growth. Foetal growth retardation has also been induced experimentally in several species using one of the following methods: (i) maternal undernutrition, (ii) chronic hypoxia, (iii) prolonged reduction in uterine blood flow, (iv) reduction in placental size, and (v) endocrine alterations. These models provide useful information on the physiological mechanisms underlying a specific type of growth retardation. These in-vivo models and in-vivo tissue culture models can now be analysed by biochemical and molecular biological techniques to unravel the basic mechanisms that underlie foetal growth retardation.
authors.affiliation: MRC Group in Fetal and Neonatal Health and Development, Lawson Research Institute, University of Western Ontario, London, Canada.
authors.forename: V K
authors.initials: VK
authors.lastname: Han
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005314:Embryonic and Fetal Development / Q000235:genetics / Q000502:physiology; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics / Q000503:physiopathology / Q000662:veterinary*; D006133:Growth Substances / Q000502:physiology*; D006734:Horse Diseases / Q000196:embryology* / Q000235:genetics / Q000503:physiopathology; D006736:Horses / Q000196:embryology* / Q000235:genetics / Q000502:physiology*; D006801:Humans; D011247:Pregnancy
chemical_list: D006133:Growth Substances