title: Assessment of in vivo fetal growth and placental vascular function in a novel intrauterine growth restriction model of progressive uterine artery occlusion in guinea pigs.
abstract: Intra-uterine growth restriction (IUGR) is associated with short and long-term metabolic and cardiovascular alterations. Mice and rats have been extensively used to study the effects of IUGR, but there are notable differences in fetal and placental physiology relative to those of humans that argue for alternative animal models. This study proposes that gradual occlusion of uterine arteries from mid-gestation in pregnant guinea pigs produces a novel model to better assess human IUGR. Fetal biometry and in vivo placental vascular function were followed by sonography and Doppler of control pregnant guinea pigs and sows submitted to surgical placement of ameroid constrictors in both uterine arteries (IUGR) at mid-gestation (35 days). The ameroid constrictors induced a reduction in the fetal abdominal circumference growth rate (0.205 cm day(-1) ) compared to control (0.241 cm day(-1) , P < 0.001) without affecting biparietal diameter growth. Umbilical artery pulsatility and resistance indexes at 10 and 20 days after surgery were significantly higher in IUGR animals than controls (P < 0.01). These effects were associated with a decrease in the relative luminal area of placental chorionic arteries (21.3 ± 2.2% vs. 33.2 ± 2.7%, P < 0.01) in IUGR sows at near term. Uterine artery intervention reduced fetal (∼30%), placental (∼20%) and liver (∼50%) weights (P < 0.05), with an increased brain to liver ratio (P < 0.001) relative to the control group. These data demonstrate that the ameroid constrictor implantations in uterine arteries in pregnant guinea pigs lead to placental vascular dysfunction and altered fetal growth that induces asymmetric IUGR.
authors.affiliation: Programa de Fisiopatología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Av. Salvador 486, Providencia, 7500922, Santiago, Chile.
authors.forename: Emilio A
authors.initials: EA
authors.lastname: Herrera
authors.affiliation: Programa de Fisiopatología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Av. Salvador 486, Providencia, 7500922, Santiago, Chile.
authors.forename: René
authors.initials: R
authors.lastname: Alegría
authors.affiliation: División de Obstetricia y Ginecología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, 8330024, Chile.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Farias
authors.affiliation: División de Pediatría, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Farah
authors.initials: F
authors.lastname: Díaz-López
authors.affiliation: División de Obstetricia y Ginecología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, 8330024, Chile.|División de Pediatría, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Cherie
authors.initials: C
authors.lastname: Hernández
authors.affiliation: División de Pediatría, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Uauy
authors.affiliation: Departments of Obstetrics and Gynaecology and Physiology and Pharmacology, Western University, London, Ontario, Canada.|Lawson Health Research Institute and Children's Health Research Institute, London, Ontario, Canada.
authors.forename: Timothy R H
authors.initials: TR
authors.lastname: Regnault
authors.affiliation: División de Obstetricia y Ginecología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 391, Santiago, 8330024, Chile.|División de Pediatría, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Paola
authors.initials: P
authors.lastname: Casanello
authors.affiliation: División de Pediatría, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Bernardo J
authors.initials: BJ
authors.lastname: Krause
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology / Q000503:physiopathology*; D006168:Guinea Pigs; D021041:Placental Circulation; D011247:Pregnancy; D055988:Uterine Artery / Q000473:pathology / Q000601:surgery*; D055357:Uterine Artery Embolization / Q000009:adverse effects / Q000379:methods*