Maternal obesogenic diet disrupts mid-gestation decidual immune and vascular homeostasis without impairing spiral artery remodelling

Bellissimo, C. J.; Yeo, E.; Ribeiro, T. A.; Jazwiec, P. A.; Ellewela, C.; Bains, J.; Ashkar, A. A.; Beristain, A. G.; Bowdish, D. M. E.; Sloboda, D. M.

doi:10.1101/2024.09.10.612284

bioRxiv · 10.1101/2024.09.10.612284

Maternal obesogenic diet disrupts mid-gestation decidual immune and vascular homeostasis without impairing spiral artery remodelling

Bellissimo, C. J.·Yeo, E.·Ribeiro, T. A.·Jazwiec, P. A.·Ellewela, C.·Bains, J.·Ashkar, A. A.·Beristain, A. G.·Bowdish, D. M. E.·Sloboda, D. M.

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Abstract

Excess maternal adiposity (i.e., overweight and obesity) during pregnancy has been linked to impaired uteroplacental perfusion, compromised placental development, and a higher risk of adverse pregnancy outcomes. Owing to the nature of chronic inflammation and immune dysregulation accompanying excess adiposity, disruption of leukocyte-mediated tissue remodelling and immunoregulation within the decidua have emerged as likely drivers contributing to suboptimal placental function in pregnancies impacted by maternal overweight or obesity. However, the impacts of excess adiposity on major populations of innate lymphoid cells (ILCs) and macrophages which orchestrate these processes and the environment that these cells occupy remain vastly understudied. Here, we used a mouse model of chronic high-fat, high-sucrose (HFHS) diet-feeding to characterize the impacts of an obesogenic milieu on decidual immune dynamics during placental development at mid-gestation (E10.5). HFHS pregnancies exhibited marked increases in total decidual leukocyte abundance, driven by population-level increases in tissue-resident and conventional NK cells, and MHC-II+ macrophages. This was not associated with abnormalities in implantation site morphology or decidual spiral artery remodelling but was coincident with histological patterns of local inflammation. In line with this, expression of canonical proinflammatory cytokines and chemokines were moderately upregulated in bulk decidual tissue of HFHS dams. This was accompanied by more potent elevations in multiple mediators of angiogenesis, endothelial activation, and coagulation in HFHS decidual tissue. Collectively, these findings point towards pathological vascular inflammation and possibly dysregulated decidual angiogenesis in the first half of pregnancy as factors predisposing to reduced placental efficiency, malperfusion, and inflammation seen in pregnancies affected by maternal overweight and obesity.

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Bellissimo, C. J., Yeo, E., Ribeiro, T. A., Jazwiec, P. A., Ellewela, C., Bains, J., Ashkar, A. A., Beristain, A. G., Bowdish, D. M. E., Sloboda, D. M.. 2024-09-12. Maternal obesogenic diet disrupts mid-gestation decidual immune and vascular homeostasis without impairing spiral artery remodelling. https://doi.org/10.1101/2024.09.10.612284

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