ABSTRACT
Increasing uterine artery blood flow (UABF) may benefit fetal growth restriction where impaired uteroplacental perfusion prevails. Based on previous short-term results, we examined the long-term effects of adenovirus vector-mediated overexpression of vascular endothelial growth factor-A(165) (VEGF-A(165)) in the uterine artery (UtA). Transit-time flow probes were implanted around both UtAs of mid-gestation pregnant sheep (n=11) to measure UABF. A carotid artery catheter was inserted to measure maternal or fetal hemodynamics. Baseline UABF was measured over 3 days, before injection of adenovirus vector (5 × 10(11) particles) encoding the VEGF-A(165) gene (Ad.VEGF-A(165)) into one UtA and a reporter ß-galactosidase gene (Ad.LacZ) contralaterally. UABF was then measured daily until term. At 4 weeks post injection, the increase in UABF was significantly higher in Ad.VEGF-A(165) compared with Ad.LacZ-transduced UtAs (36.53% vs 20.08%, P=0.02). There was no significant effect on maternal and fetal blood pressure. Organ bath studies showed significantly lesser vasoconstriction (E(max) 154.1 vs 184.7, P<0.001), whereas immunohistochemistry demonstrated a significantly increased number of adventitial blood vessels (140 vs 91, n=26, P<0.05) following Ad.VEGF-A(165) transduction. Local overexpression of VEGF-A(165) in the UtAs of pregnant mid-gestation sheep leads to a sustained long-term increase in UABF, which may be explained by neovascularization and altered vascular reactivity.
Subject(s)
Pregnancy, Animal , Uterine Artery/metabolism , Uterus/blood supply , Vascular Endothelial Growth Factor A/genetics , Adenoviridae/genetics , Animals , Arterial Pressure , Female , Fetal Growth Retardation/physiopathology , Genetic Vectors , Pregnancy , Pregnancy Complications , Regional Blood Flow , Sheep , Vascular Endothelial Growth Factor A/metabolismABSTRACT
Impaired materno-placental perfusion causes two important obstetric complications, fetal growth restriction and preeclampsia. This study investigated whether adenoviral vector-mediated overexpression of vascular endothelial growth factor (VEGF) in the uterine arteries (UtAs) increases uterine artery blood flow (UBF). First-generation adenovirus vectors (5 x 10(11) particles) containing the VEGF gene (Ad.VEGF-A or -D) or the beta-galactosidase reporter gene (Ad.lacZ) were injected into the UtAs of pregnant sheep (n=6) at 88-102 days of gestation (term=145 days). UBF was measured using Doppler sonography before, and 4-7 days after injection. Mean UBF increased significantly from 233+/-156 (s.d.) ml min(-1) to 753+/-415 ml min(-1) following Ad.VEGF-A injection (P=0.005, n=5); Ad.lacZ infection had no significant effect. Organ bath experiments on uterine arterial sections 4-7 days after injection showed that, compared with Ad.lacZ vessels, Ad.VEGF-A-transduced vessels had a reduced contractile response to phenylephrine (E max 148+/-10.9 vs E max 228.2+/-27.5, P<0.05) but increased relaxation with bradykinin (pD2 (-log EC50) values 9.11+/-0.01 vs 8.65+/-0.11, P<0.05). Injection of Ad.VEGF-A into the UtAs increases UBF by enhancing vasodilatation. This may provide the basis for therapy in pregnancies complicated by uteroplacental insufficiency.
Subject(s)
Adenoviridae/genetics , Fetal Growth Retardation/therapy , Genetic Therapy/methods , Genetic Vectors/administration & dosage , Transduction, Genetic/methods , Vascular Endothelial Growth Factor A/genetics , Animals , Arteries , Enzyme-Linked Immunosorbent Assay , Female , Fetal Growth Retardation/physiopathology , Gene Expression , Genetic Vectors/genetics , Injections, Intravenous , Models, Animal , Placental Circulation , Pregnancy , Regional Blood Flow , Reverse Transcriptase Polymerase Chain Reaction , Sheep , Ultrasonography , Uterus/diagnostic imaging , Vascular Endothelial Growth Factor A/analysis , Vasodilation/geneticsABSTRACT
This study was carried out on 968 skull X-rays to determine the incidence of the metopic suture in the Lebanese population. Complete and incomplete metopism was present in 0.82% and 0.93% of cases, respectively, leading to an overall incidence of 1.75%. In both categories, the incidence was relatively higher in males (1.84%) than in females (1.62%). Persons living in rural areas had a higher incidence of complete and incomplete metopism compared to persons living in urban areas, with ratios of 4:1 and 4:2, respectively. Other findings included an absence of frontal sinuses in all but one skull with complete metopism, accessory ossicles in the majority of cases of complete metopism (7/8), and hydrocephalus in one case. Medical records did not reveal any other associated diseases or abnormalities. Despite the low incidence of metopic suture in the Lebanese population, in X-ray diagnosis of fractures of the frontal bone, metopic suture must not be ruled out.
