Placental Hypoxia During Early Pregnancy Causes Maternal Hypertension and Placental Insufficiency in the Hypoxic Guinea Pig Model

Abstract

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.

Intermittent hypoxia impairs uterine artery function in pregnant mice

“…We speculate that our cyclic hypoxic profile (12% ) was not severe enough to prevent proper trophoblast invasion, as results in a pig model of hypoxia demonstrated that while a hypoxic exposure of 10.2% impaired trophoblast invasion and placental damage, there was little or no effect when was 16% or 12% during pregnancy (Thompson et al . ).…”

Technical Feasibility and Physiological Relevance of Hypoxic Cell Culture Models

“…Humans as well as animals can be exposed to hypobaric (HH) or normobaric hypoxia (NH) in order to study wide variety of diseases, including pulmonary hypertension (20), reoxygenation injury (21), pre-eclampsia (22), hypoxic insult of the brain (23), and diabetic retinopathy (24). While HH, which physically resembles a high-altitude environment, is induced by decreasing atmospheric pressure under 101 325 Pa (1 atm, 760 mm hg) typically in a tightly sealed hypobaric chamber (25), NH exposure is based on the reduction of the partial pressure of oxygen (pO 2 ) at normal atmospheric pressure, which typically occurs through the administration of nitrogen to a face mask (26), hypoxic tent (27), or environmental chamber (22,23).…”

Toxicity Effect by Binahong (Anredera cordifolia) Leaf Extract in Histopathology and Liver Weight of Guinea Pigs (Cavia cobaya)

“…Animal surgical procedures and sampling. C. cobaya has treatmented for 10 days prepartum, then postpartum first day was performed dislocation using overdose anesthesia (Thompson et al, 2016) and was followed by rapid surgery to remove the liver organs. Liver organs was stored in 10% formalin solution to histopathology and toxicity testing (Thompson et al, 2016;Samik and Safitri, 2017).…”

“…The tissue sheets were immersed in eosin hematoxylin for 10 minutes and rinsed with running water (Cakir et al, 2015). Then, 96% alcohol (I), alcohol 96% (II), absolute alcohol (III), absolute alcohol (Nithianantham et al, 2011) was washed for 3 min followed by xylol (Thompson et al, 2016;Cakir et al, 2015;Pradana et al, 2016).…”