Hofbauer cell function in the term placenta associates with adult cardiovascular and depressive outcomes

Hofbauer cell function in the term placenta associates with adult cardiovascular and depressive outcomes

Nature Communications

10.1038/s41467-023-42300-8

https://doi.org/10.1038/s41467-023-42300-8

Eamon Fitzgerald, Mojun Shen, Hannah Ee Juen Yong, Zihan Wang, Irina Pokhvisneva, Sachin Patel, Nicholas O’Toole, Shiao-Yng Chan, Yap Seng Chong, Helen Chen, Peter D. Gluckman, Jerry Chan, Patrick Kia Ming Lee, Michael J. Meaney

placenta, Cardiovascular, depression, Hofbauer cell, inflammation

14 November 2023

Fitzgerald, E., Shen, M., Yong, H. E. J., Wang, Z., Pokhvisneva, I., Patel, S., O’Toole, N., Chan, S.-Y., Chong, Y. S., Chen, H., Gluckman, P. D., Chan, J., Lee, P. K. M., & Meaney, M. J. (2023). Hofbauer cell function in the term placenta associates with adult cardiovascular and depressive outcomes. Nature Communications, 14(1). https://doi.org/10.1038/s41467-023-42300-8

Pathological placental inflammation increases the risk for several adult disorders, but these mediators are also expressed under homeostatic conditions, where their contribution to adult health outcomes is unknown. Here we define an inflammation-related expression signature, primarily expressed in Hofbauer cells of the term placenta and use expression quantitative trait loci to create a polygenic score (PGS) predictive of its expression. Using this PGS in the UK Biobank we conduct a phenome-wide association study, followed by Mendelian randomization and identify protective, sex-dependent effects of the placental module on cardiovascular and depressive outcomes. Genes differentially regulated by intra-amniotic infection and preterm birth are over-represented within the module. We also identify aspirin as a putative modulator of this inflammation-related signature. Our data support a model where disruption of placental Hofbauer cell function, due to preterm birth or prenatal infection, contributes to the increased risk of depression and cardiovascular disease observed in these individuals.

Attribution 4.0 International (CC BY 4.0)

This research is supported by core funding from: Institute for Human Development and Potential
Grant Reference no. :

Funding for this study was provided through funding of the Depression Task Force of the Hope for Depression Research Foundation to MJM.

https://oar.a-star.edu.sg/communities-collections/articles/21982

2041-1723

Institute for Human Development and Potential

https://doi.org/10.1038/s41467-023-42300-8