title: Maternal nutrient restriction in guinea pigs leads to fetal growth restriction with evidence for chronic hypoxia.
abstract: BackgroundWe determined whether maternal nutrient restriction (MNR) in guinea pigs leading to fetal growth restriction (FGR) impacts markers for tissue hypoxia, implicating a mechanistic role for chronic hypoxia.MethodsGuinea pigs were fed ad libitum (Control) or 70% of the control diet before pregnancy, switching to 90% at mid-pregnancy (MNR). Near term, hypoxyprobe-1 (HP-1), a marker of tissue hypoxia, was injected into pregnant sows. Fetuses were then necropsied and liver, kidney, and placental tissues were processed for erythropoietin (EPO), EPO-receptor (EPOR), and vascular endothelial growth factor (VEGF) protein levels, and for HP-1 immunoreactivity (IR).ResultsFGR-MNR fetuses were 36% smaller with asymmetrical growth restriction compared to controls. EPO and VEGF protein levels were increased in the female FGR-MNR fetuses, providing support for hypoxic stimulus and linkage to increased erythropoiesis, but not in the male FGR-MNR fetuses, possibly reflecting a weaker link between oxygenation and erythropoiesis. HP-1 IR was increased in the liver and kidneys of both male and female FGR-MNR fetuses as an index of local tissue hypoxia, but with no changes in the placenta.ConclusionChronic hypoxia is likely to be an important signaling mechanism for the decreased fetal growth seen with maternal undernutrition and appears to be post-placental in nature.
authors.affiliation: Department of Obstetrics and Gynecology, University of Western Ontario, London, Ontario, Canada.|Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Elias
authors.affiliation: Department of Obstetrics and Gynecology, University of Western Ontario, London, Ontario, Canada.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Maki
authors.affiliation: Department of Obstetrics and Gynecology, University of Western Ontario, London, Ontario, Canada.
authors.forename: Brad
authors.initials: B
authors.lastname: Matushewski
authors.affiliation: Biotron Experimental Climate Change Research Centre, University of Western Ontario, London, Ontario, Canada.
authors.forename: Karen
authors.initials: K
authors.lastname: Nygard
authors.affiliation: Department of Obstetrics and Gynecology, University of Western Ontario, London, Ontario, Canada.|Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada.|Children's Health Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
authors.forename: Timothy R H
authors.initials: TRH
authors.lastname: Regnault
authors.affiliation: Department of Obstetrics and Gynecology, University of Western Ontario, London, Ontario, Canada.|Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada.|Department of Pediatrics, University of Western Ontario, London, Ontario, Canada.|Children's Health Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada.
authors.forename: Bryan S
authors.initials: BS
authors.lastname: Richardson
mesh_terms: D000818:Animals; D015331:Cohort Studies; D004921:Erythropoietin / Q000378:metabolism; D005260:Female; D047109:Fetal Development; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D006168:Guinea Pigs; D000860:Hypoxia / Q000503:physiopathology*; D007150:Immunohistochemistry; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D008431:Maternal-Fetal Exchange; D009593:Nitroimidazoles / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D009593:Nitroimidazoles; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin; C033815:pimonidazole