Mechanism Sharing Between Genetic and Gestational Hypoxia-Induced Cardiac Anomalies

Frontiers in Cardiovascular Medicine
Olivia MoumneHideko Kasahara

Abstract

Background: Cardiac development is a dynamic process both temporally and spatially. These complex processes are often disturbed and lead to congenital cardiac anomalies that affect approximately 1% of live births. Disease-causing variants in several genetic loci lead to cardiac anomalies, with variants in transcription factor NKX2-5 gene being one of the largest variants known. Gestational hypoxia, such as seen in high-altitude pregnancy, has been known to affect cardiac development, yet the incidence and underlying mechanisms are largely unknown. Methods and Results: Normal wild-type female mice mated with heterozygous Nkx2-5 mutant males were housed under moderate hypoxia (14% O2) or normoxia (20.9% O2) conditions from 10.5 days of gestation. Wild-type mice exposed to hypoxia demonstrate excessive trabeculation, ventricular septal defects, irregular morphology of interventricular septum as well as atrial septal abnormalities, which overlap with those seen in heterozygous Nkx2-5 mutant mice. Genome-wide transcriptome done by RNA-seq of a 2-day hypoxic exposure on wild-type embryos revealed abnormal transcriptomes, in which approximately 60% share those from Nkx2-5 mutants without hypoxia. Gestational hypoxia reduced the expres...Continue Reading

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Citations

Jan 5, 2020·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Lawrence X CaiHideko Kasahara
Sep 25, 2019·Cold Spring Harbor Perspectives in Biology·Jacinta Isabelle Kalisch-SmithDuncan Burnaby Sparrow
Feb 23, 2019·Development·Julie L M MoreauSally L Dunwoodie
Mar 25, 2021·Scientific Reports·Cassandra F DollHideko Kasahara

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Methods Mentioned

BETA
dissect
RNA-seq

Software Mentioned

SPSS
Image J
Permut Matrix
Samstat
FastQ
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