title: Fetal adrenal demedullation lowers circulating norepinephrine and attenuates growth restriction but not reduction of endocrine cell mass in an ovine model of intrauterine growth restriction.
abstract: Placental insufficiency is associated with fetal hypoglycemia, hypoxemia, and elevated plasma norepinephrine (NE) that become increasingly pronounced throughout the third trimester and contribute to intrauterine growth restriction (IUGR). This study evaluated the effect of fetal adrenal demedullation (AD) on growth and pancreatic endocrine cell mass. Placental insufficiency-induced IUGR was created by exposing pregnant ewes to elevated ambient temperatures during mid-gestation. Treatment groups consisted of control and IUGR fetuses with either surgical sham or AD at 98 days gestational age (dGA; term = 147 dGA), a time-point that precedes IUGR. Samples were collected at 134 dGA. IUGR-sham fetuses were hypoxemic, hypoglycemic, and hypoinsulinemic, and values were similar in IUGR-AD fetuses. Plasma NE concentrations were ~5-fold greater in IUGR-sham compared to control-sham, control-AD, and IUGR-AD fetuses. IUGR-sham and IUGR-AD fetuses weighed less than controls. Compared to IUGR-sham fetuses, IUGR-AD fetuses weighed more and asymmetrical organ growth was absent. Pancreatic β-cell mass and α-cell mass were lower in both IUGR-sham and IUGR-AD fetuses compared to controls, however, pancreatic endocrine cell mass relative to fetal mass was lower in IUGR-AD fetuses. These findings indicate that NE, independently of hypoxemia, hypoglycemia and hypoinsulinemia, influence growth and asymmetry of growth but not pancreatic endocrine cell mass in IUGR fetuses.
authors.affiliation: School of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, AZ 85721, USA. melissaad@email.arizona.edu.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Davis
authors.affiliation: School of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, AZ 85721, USA. tonymacko@gmail.com.
authors.forename: Antoni R
authors.initials: AR
authors.lastname: Macko
authors.affiliation: School of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, AZ 85721, USA. penrodl@email.arizona.edu.
authors.forename: Leah V
authors.initials: LV
authors.lastname: Steyn
authors.affiliation: School of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, AZ 85721, USA. miranda1@email.arizona.edu.
authors.forename: Miranda J
authors.initials: MJ
authors.lastname: Anderson
authors.affiliation: School of Animal and Comparative Biomedical Sciences, The University of Arizona, Tucson, AZ 85721, USA. limesand@ag.arizona.edu.
authors.forename: Sean W
authors.initials: SW
authors.lastname: Limesand
mesh_terms: D000311:Adrenal Glands / Q000503:physiopathology* / Q000601:surgery; D000818:Animals; D001344:Autopsy; D002395:Catecholamines / Q000009:adverse effects / Q000378:metabolism; D049109:Cell Proliferation / Q000502:physiology; D004195:Disease Models, Animal; D055098:Endocrine Cells / Q000378:metabolism*; D005260:Female; D005317:Fetal Growth Retardation / Q000097:blood* / Q000503:physiopathology; D005333:Fetus / Q000503:physiopathology*; D007003:Hypoglycemia / Q000209:etiology / Q000503:physiopathology; D000860:Hypoxia / Q000209:etiology / Q000503:physiopathology; D050417:Insulin-Secreting Cells / Q000473:pathology; D009638:Norepinephrine / Q000097:blood*; D010927:Placental Insufficiency / Q000503:physiopathology; D011247:Pregnancy; D012756:Sheep
chemical_list: D002395:Catecholamines; D009638:Norepinephrine