Placental Hypoxia During Early Pregnancy Causes Maternal Hypertension and Placental Insufficiency in the Hypoxic Guinea Pig Model.
Chronic placental hypoxia is one of the root causes of placental insufficiencies that result in pre-eclampsia and maternal hypertension. Chronic hypoxia causes disruption of trophoblast (TB) development, invasion into maternal decidua, and remodeling of maternal spiral arteries. The pregnant guinea pig shares several characteristics with humans such as hemomonochorial placenta, villous subplacenta, deep TB invasion, and remodeling of maternal arteries, and is an ideal animal model to study placental development. We hypothesized that chronic placental hypoxia of the pregnant guinea pig inhibits TB invasion and alters spiral artery remodeling. Time-mated pregnant guinea pigs were exposed to either normoxia (NMX) or three levels of hypoxia (HPX: 16%, 12%, or 10.5% O2) from 20 day gestation until midterm (39-40 days) or term (60-65 days). At term, HPX (10.5% O2) increased maternal arterial blood pressure (HPX 57.9 ± 2.3 vs. NMX 40.4 ± 2.3, P < 0.001), decreased fetal weight by 16.1% (P < 0.05), and increased both absolute and relative placenta weights by 10.1% and 31.8%, respectively (P < 0.05). At midterm, there was a significant increase in TB proliferation in HPX placentas as confirmed by increased PCNA and KRT7 staining and elevated ESX1 (TB marker) gene expression (P < 0.05). Additionally, quantitative image analysis revealed decreased invasion of maternal blood vessels by TB cells. In summary, this animal model of placental HPX identifies several aspects of abnormal placental development, including increased TB proliferation and decreased migration and invasion of TBs into the spiral arteries, the consequences of which are associated with maternal hypertension and fetal growth restriction.
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland, Baltimore, Maryland lthompson1@umm.edu.|University of Maryland School of Medicine, Baltimore, Maryland.
Loren P
LP
Thompson
Animal Biosciences and Biotechnology Laboratory, USDA-ARS, Beltsville, Maryland.|Animal and Avian Science, University of Maryland, College Park, Maryland.
Laramie
L
Pence
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland, Baltimore, Maryland.|University of Maryland School of Medicine, Baltimore, Maryland.
Gerald
G
Pinkas
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland, Baltimore, Maryland.|University of Maryland School of Medicine, Baltimore, Maryland.
Hong
H
Song
Animal Biosciences and Biotechnology Laboratory, USDA-ARS, Beltsville, Maryland btelugu@umd.edu.|Animal and Avian Science, University of Maryland, College Park, Maryland.
Bhanu P
BP
Telugu
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D006168:Guinea Pigs; D046110:Hypertension, Pregnancy-Induced / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D000860:Hypoxia / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D053552:Keratin-7 / Q000378:metabolism; D009929:Organ Size / Q000502:physiology; D010920:Placenta / Q000378:metabolism* / Q000503:physiopathology; D010927:Placental Insufficiency / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D010929:Placentation; D011247:Pregnancy; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D066253:Vascular Remodeling / Q000502:physiology
D053552:Keratin-7; D018809:Proliferating Cell Nuclear Antigen
animal model; hypoxia; maternal hypertension; placental insufficiency; pregnancy