CSH RNA Interference Reduces Global Nutrient Uptake and Umbilical Blood Flow Resulting in Intrauterine Growth Restriction

Autor: Russell V. Anthony, Amelia R Tanner, Asghar Ali, Quinton A Winger, Victoria C Kennedy, Cameron S Lynch, Paul J. Rozance
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
Male
Placenta
Uterus
nutrient uptake
Intrauterine growth restriction
Hemodynamics
Somatomammotropin
0302 clinical medicine
Pregnancy
blood flow
Biology (General)
Insulin-Like Growth Factor I
RNA
Small Interfering
Spectroscopy
reproductive and urinary physiology
Fetal Growth Retardation
Chemistry
Gestational age
General Medicine
Fetal Blood
Computer Science Applications
medicine.anatomical_structure
embryonic structures
Female
RNA Interference
Signal Transduction
intrauterine growth restriction
QH301-705.5
030209 endocrinology & metabolism
Gestational Age
Catalysis
Article
Inorganic Chemistry
Andrology
03 medical and health sciences
Fetus
chorionic somatomammotropin
medicine
Animals
Physical and Theoretical Chemistry
QD1-999
Molecular Biology
Sheep
uterus
urogenital system
Organic Chemistry
fungi
Transplacental
Ultrasonography
Doppler
Nutrients
medicine.disease
Placental Lactogen
030104 developmental biology
Blastocyst
Glucose
Hormone
Zdroj: International Journal of Molecular Sciences
Volume 22
Issue 15
International Journal of Molecular Sciences, Vol 22, Iss 8150, p 8150 (2021)
ISSN: 1422-0067
DOI: 10.3390/ijms22158150
Popis: Deficiency of the placental hormone chorionic somatomammotropin (CSH) can lead to the development of intrauterine growth restriction (IUGR). To gain insight into the physiological consequences of CSH RNA interference (RNAi), the trophectoderm of hatched blastocysts (nine days of gestational age
dGA) was infected with a lentivirus expressing either a scrambled control or CSH-specific shRNA, prior to transfer into synchronized recipient sheep. At 90 dGA, umbilical hemodynamics and fetal measurements were assessed by Doppler ultrasonography. At 120 dGA, pregnancies were fitted with vascular catheters to undergo steady-state metabolic studies with the 3H2O transplacental diffusion technique at 130 dGA. Nutrient uptake rates were determined and tissues were subsequently harvested at necropsy. CSH RNAi reduced (p ≤ 0.05) both fetal and uterine weights as well as umbilical blood flow (mL/min). This ultimately resulted in reduced (p ≤ 0.01) umbilical IGF1 concentrations, as well as reduced umbilical nutrient uptakes (p ≤ 0.05) in CSH RNAi pregnancies. CSH RNAi also reduced (p ≤ 0.05) uterine nutrient uptakes as well as uteroplacental glucose utilization. These data suggest that CSH is necessary to facilitate adequate blood flow for the uptake of oxygen, oxidative substrates, and hormones essential to support fetal and uterine growth.
Databáze: OpenAIRE
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