title: In utero development of fetal thirst and appetite: potential for programming.
abstract: Thirst and appetite-mediated ingestive behavior develop and are likely programmed in utero, thus preparing for newborn and adult ingestive behavior. Fetal swallowing activity is markedly different from that of the adult, as spontaneous fetal swallowing occurs at a markedly (six-fold) higher rate compared with spontaneous adult drinking activity. This high rate of fetal swallowing is critical for the regulation of amniotic fluid volume and the development of the fetal gastrointestinal tract. Disordered fetal swallowing has been associated with both a decrease (oligohydramnios) and increase (polyhydramnios) in amniotic fluid volume. Both conditions are associated with a significant increase in perinatal morbidity and mortality, and limited treatment modalities are currently available. The mechanisms underlying the high rate of human fetal swallowing are regulated, in part, by tonic activity of central angiotensin II, glutamate N-methyl-D-aspartate receptors, and neuronal nitric oxide synthase. Fetal hypertonicity-mediated dipsogenesis is likely programmed in utero, as offspring of water-restricted ewes demonstrate a programmed syndrome of plasma hypertonicity, with significant hematologic and cardiovascular alterations. Similar to dipsogenic mechanisms, peripheral and central fetal orexic mechanisms also develop in utero, as demonstrated by increased fetal swallowing after both oral sucrose infusion and central injection of neuropeptide Y. The role of leptin in regulating fetal ingestive behavior is interesting because, contrary to actions in adults, leptin does not suppress fetal ingestive behavior. Teleologically, this may be of value during the newborn period, as unopposed appetite stimulatory mechanisms may facilitate rapid fetal and newborn weight gain. An adverse intrauterine environment, with altered fetal orexic factors during the critical developmental period of fetal life, may alter the normal setpoints of appetitive behavior and potentially lead to programming of adulthood hyperphagia and obesity. Further research is needed to delineate the mechanistic relationship between the intrauterine environment and the development of the setpoints of adult appetite and thirst.
authors.affiliation: Perinatal Research Laboratories, Harbor/UCLA Medical Center, UCLA School of Medicine, Los Angeles, California, USA. melhaddad@gcrc.rei.edu
authors.forename: M A
authors.initials: MA
authors.lastname: El-Haddad
authors.forename: M
authors.initials: M
authors.lastname: Desai
authors.forename: D
authors.initials: D
authors.lastname: Gayle
authors.forename: M G
authors.initials: MG
authors.lastname: Ross
mesh_terms: D000818:Animals; D001066:Appetite; D003679:Deglutition; D005314:Embryonic and Fetal Development; D005260:Female; D005333:Fetus / Q000502:physiology*; D006801:Humans; D020738:Leptin / Q000502:physiology; D009478:Neuropeptide Y / Q000502:physiology; D016104:Oligohydramnios; D006831:Polyhydramnios; D011247:Pregnancy; D012996:Solutions; D013395:Sucrose / Q000008:administration & dosage; D013894:Thirst
chemical_list: D020738:Leptin; D009478:Neuropeptide Y; D012996:Solutions; D013395:Sucrose