Omics · study · 2026
PDHA1 Crotonylation Is Essential for Endometrial Metabolic Reprogramming and Decidualization in Normal Pregnancy
Listed in NCBI GEO
Endometrial decidualization is essential for pregnancy.
Description
Impaired decidualization is a hallmark of preeclampsia (PE), yet the underlying mechanisms remain unclear. Herewe show that uterine pyruvate dehydrogenase E1 subunit α (PDHA1) K385 crotonylation (K385cr) is crucial in metabolic reprogramming and decidualization.
In PE women, decidual PDHA1 K385cr is markedly reduced. In mice, Pdha1 K385cr deficiency causes endometrial metabolic dysregulation, poor decidualization, and a PE-like phenotype. Mechanistically, crotonylation promotes PDHA1 phosphorylation, inhibiting pyruvate dehydrogenase activity and enhancing glycolysis and NAD+ generation.
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In turn, NAD+ increases SIRT2-mediated FOXO1 deacetylation and nuclear translocation, upregulating decidual gene expression. In Pdha1 K385cr deficient mice, treatment of the NAD⁺ precursor β-NMN enhances the NAD⁺-SIRT2 FOXO1 pathway and decidualization, alleviating the PE-like phenotype. Our results indicate that PDHA1 K385cr is a key metabolic regulator in the pregnant uterus and that impaired PDHA1 K385cr may contribute to PE, suggesting that enhancing the NAD⁺-SIRT2-FOXO1 pathway may be exploited for PE intervention.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE327nnn/GSE327790 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE327790 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1452785 ncbi.nlm.nih.gov/bioproject/PRJNA1452785 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
Provenance · 1 source records, 7 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE327790 | 15 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |