Hypoxia in extravillous trophoblasts links maternal obesity and offspring neurobehavior.
| Publication Type | Academic Article |
| Authors | Gunter-Rahman F, Mallett S, White F, Jacques P, Raju R, Hivert M, Lee E |
| Journal | iScience |
| Volume | 28 |
| Issue | 6 |
| Pagination | 112636 |
| Date Published | 05/12/2025 |
| ISSN | 2589-0042 |
| Abstract | While maternal obesity (MO) is associated with neurobehavioral impairment (NBI) in offspring, the underlying mechanisms remain unknown. The placenta is thought to play a role in fetal programming. To elucidate the association between MO and offspring NBI, we performed single-nucleus RNA-seq on maternal- and fetal-facing sides of human term placentas from MO and lean groups. MO placentas showed the upregulation of hypoxia response genes in multiple cell types, and maternal-facing hypoxia gene expression correlated with offspring NBI in an independent birth cohort, Gen3G. Extravillous trophoblasts (EVTs) showed the highest expression of NBI-correlated genes, and EVT NBI-gene expression correlated with hypoxia signatures in two cohorts. Exposing cultured EVTs to hypoxia increased NBI gene expression, and 44% of the association between maternal BMI and NBI-gene expression in EVTs was mediated by hypoxia. Our findings suggest that hypoxia in EVTs is a key process in the neurodevelopmental programming of fetal exposure to MO. |
| DOI | 10.1016/j.isci.2025.112636 |
| PubMed ID | 40502709 |
| PubMed Central ID | PMC12152354 |