PXD062087-1

PXD062087 is an original dataset announced via ProteomeXchange.

Title	The Role of Maternal Obesity in Offspring Cardiovascular Development and Congenital Heart Defects
Description	Background: Congenital heart disease (CHD) is a leading cause of death in newborns, yet many of its molecular mechanisms remain unknown. Both maternal obesity and diabetes increase the risk of CHD in offspring, with recent studies suggesting these conditions may have distinct teratogenic mechanisms. The global prevalence of obesity is rising, and while maternal obesity is a known risk factor for fetal CHD, the specific mechanisms are largely unexplored. Methods: We used a murine model of diet-induced maternal obesity, without diabetes, to produce dams that were overweight but had normal blood glucose levels. Embryos were generated and their developing hearts analyzed. Transcriptome analysis was performed using single-nuclei (snRNAseq) and bulk RNA sequencing (RNA-seq). Global and phospho-enriched proteome analysis was performed using tandem-mass tag mass spectroscopy (TMT-MS). Immunobloting and histologic evaluation were also performed. Results: Analysis revealed disrupted oxidative phosphorylation and reactive oxygen species formation, with reduced antioxidant capacity, evidenced by downregulation of genes Sod1 and Gp4x, and disrupted Hif1a signaling. Evidence of oxidative stress, cell death signaling, and alteration in Rho GTPase and actin cytoskeleton signaling was also observed. Genes involved in cardiac morphogenesis, including Hand2, were downregulated, and fewer mature cardiomyocytes were present. Histologic analysis confirmed increased cardiac defects in embryos exposed to maternal obesity. Conclusion: These findings demonstrate maternal obesity alone can result in cardiac defects through mechanisms similar to those associated with maternal hyperglycemia. This study provides valuable insights into the role of maternal obesity, a growing and modifiable risk factor, in the development of the most common birth defect, CHD.
HostingRepository	PRIDE
AnnounceDate	2025-06-30
AnnouncementXML	Submission_2025-06-29_16:11:52.208.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD062087
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Emma Doud
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Eclipse

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-20 11:48:00	ID requested
⏵ 1	2025-06-29 16:11:53	announced

McMullan A, Zwierzynski JB, Jain N, Haneline LS, Shou W, Kua KL, Hota SK, Durbin MD, Role of Maternal Obesity in Offspring Cardiovascular Development and Congenital Heart Defects. J Am Heart Assoc, 14(9):e039684(2025) [pubmed]

10.6019/PXD062087;

10.1161/jaha.124.039684;

submitter keyword: cardiac development,Congenital heart disease, gene-environment interaction, maternal obesity

Amber Mosley
contact affiliation	Indiana University School of Medicine, USA
contact email	almosley@iu.edu
lab head
Emma Doud
contact affiliation	Indiana University School of Medicine
contact email	edoud@iu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD062087
     1. Label: PRIDE project
     2. Name: The Role of Maternal Obesity in Offspring Cardiovascular Development and Congenital Heart Defects