Biology subjects

DeRuiter, M. C.

Publications and source records attributed to DeRuiter, M. C..

2 recordsLinked to original sources

bioRxiv2025

Haploinsufficiency of eNOS mitigates beneficial effects of maternal exercise on fetal heart development during pregestational diabetes

BackgroundPregestational diabetes (PGD) increases congenital heart defect (CHD) risk over five-fold. Maternal exercise enhances endothelial nitric oxide synthase (eNOS) activity, benefiting embryos, though its causal role remains unclear. This study investigated eNOSs role in maternal exercise-mediated protection of fetal heart development in a PGD mouse model. MethodsPGD was induced in eNOS+/- or wild-type (WT) female mice via streptozotocin before breeding with WT or eNOS+/- males. Pregnant females had access to a running wheel for voluntary exercise or remained sedentary. Fetuses were collected at embryonic day (E) 18.5 for genotyping and CHD assessment. E12.5 hearts were analyzed for proliferation, apoptosis, oxidative stress, and eNOS protein levels. ResultsMaternal exercise normalized litter size and mortality rates in offspring of diabetic eNOS+/- females but did not reduce CHD incidence in offspring of WT or eNOS+/- females with PGD. CHDs included septal defects, double outlet right ventricle, and valve defects. Exercise increased coronary artery density but not capillary density. Proliferation deficits at E12.5 were restored by exercise, yet oxidative stress remained elevated. Maternal exercise in eNOS+/- dams during PGD did not significantly change eNOS protein levels in both eNOS+/+ and eNOS+/- fetal hearts. Offspring genotype did not impact CHD incidence, cell proliferation, apoptosis or oxidative stress. ConclusionsMaternal exercise does not prevent CHDs in PGD offspring of eNOS+/- mice. Its ability to mitigate PGD-induced oxidative stress is eNOS-dependent and essential for improving heart morphology. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=178 SRC="FIGDIR/small/647329v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@4c9e4forg.highwire.dtl.DTLVardef@2d60fforg.highwire.dtl.DTLVardef@13b2d72org.highwire.dtl.DTLVardef@249a0c_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2020

Pulmonary ductal coarctation and left pulmonary artery interruption; pathology and role of neural crest and second heart field during development

ObjectivesIn congenital heart malformations with pulmonary stenosis to atresia an abnormal lateral ductus arteriosus to left pulmonary artery connection can lead to a localised narrowing (pulmonary ductal coarctation) or even interruption We investigated embryonic remodelling and pathogenesis of this area. Material and methods. Normal development was studied in WntCre reporter mice (E10.0-12.5) for neural crest cells and Nkx2.5 immunostaining for second heart field cells. Data were compared to stage matched human embryos and a VEGF120/120 mutant mouse strain developing pulmonary atresia. ResultsNormal mouse and human embryos showed that the mid-pharyngeal endothelial plexus, connected side-ways to the 6th pharyngeal arch artery. The ventral segment formed the proximal pulmonary artery. The dorsal segment (future DA) was solely surrounded by neural crest cells. The ventral segment had a dual outer lining with neural crest and second heart field cells, while the distal pulmonary artery was covered by none of these cells. The asymmetric contribution of second heart field to the future pulmonary trunk on the left side of the aortic sac (so-called pulmonary push) was evident. The ventral segment became incorporated into the pulmonary trunk leading to a separate connection of the left and right pulmonary arteries. The VEGF120/120 embryos showed a stunted pulmonary push and a variety of vascular anomalies. SummarySide-way connection of the DA to the left pulmonary artery is a congenital anomaly. The primary problem is a stunted development of the pulmonary push leading to pulmonary stenosis/atresia and a subsequent lack of proper incorporation of the ventral segment into the aortic sac. Clinically, the aberrant smooth muscle tissue of the ductus arteriosus should be addressed to prohibit development of severe pulmonary ductal coarctation or even interruption of the left pulmonary artery.

developmental biology↗