Placental network differences among obstetric syndromes identified with an integrated multiomics approach
The placenta is essential for pregnancy, and its dysfunction can harm both mother and fetus. To better understand placental physiology and its disruption in disease, we employ a multiomics approach (transcriptomics, metabolomics, and proteomics) combined with clinical data and histopathology from 321 placentas across conditions: severe fetal growth restriction (FGR), FGR with hypertension (FGR + HDP), severe preeclampsia (PE), and spontaneous preterm delivery (PTD). Cellular deconvolution reveals FGR + HDP placentas have more extravillous trophoblasts than controls (p < 0.0001). After adjusting for fetal sex and gestational age, we build condition-specific interomics networks and detect communities (a.k.a. subnetworks). In a control community, miR-365a-3p is the most connected node, whereas in FGR + HDP placentas, it is hypoxia-induced miR-210-3p. From this community, we identify a signature containing mRNAs implicated in placental dysfunction (e.g. FLT1, FSTL3, HTRA4, LEP, and PHYHIP), which distinguishes FGR + HDP placentas from those with other conditions, illustrating the power of interomics in understanding obstetric syndromes.
Authors
- Samantha N. Piekos (ORCID: https://orcid.org/0000-0002-8119-6724)
- Nathan D. Price (ORCID: https://orcid.org/0000-0002-4157-0267)
- Andrew Baumgartner (ORCID: https://orcid.org/0009-0008-8463-1219)
- Jennifer Hadlock (ORCID: https://orcid.org/0000-0001-6103-7606)
- Tianjiao Chu (ORCID: https://orcid.org/0000-0001-9644-771X)
- Yoel Sadovsky (ORCID: https://orcid.org/0000-0003-2969-6737)
- Leroy Hood (ORCID: https://orcid.org/0000-0001-7158-3678)
- Oren Barak (ORCID: https://orcid.org/0000-0002-7508-825X)
- W. Tony Parks (ORCID: https://orcid.org/0000-0001-7341-3277)
Institutions
- Program for Appropriate Technology in Health (US)
- Buck Institute for Research on Aging (US)
- University of Pittsburgh (US)
- North Seattle College (US)
- Kaplan Medical Center (IL)
- University of Washington Medical Center (US)
- Canada Research Chairs (CA)
- Institute for Systems Biology (US)
- Magee-Womens Research Institute (US)
- Hamilton Thorne (United States) (US)
- Craft Engineering Associates (United States) (US)
- University of Pennsylvania (US)
- Stanford University (US)
Publication Details
- Journal
- Communications Biology
- Published
- 2025-08-18
- DOI
- https://doi.org/10.1038/s42003-025-08631-6
- Primary Topic
- Pregnancy and preeclampsia studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Richard King Mellon Foundation
- Eunice Kennedy Shriver National Institute of Child Health and Human Development