Hofbauer Cell Disruptions Tied to Cardiovascular and Depression Risks

Research led by McGill University in Canada suggests that disruptions in Hofbauer cell function during preterm birth or intra-amniotic infection may contribute to traits associated with increased risk factors for cardiovascular disease and depression in offspring. Despite not finding a direct correlation in outcomes, the study delves into the complex interplay between placental inflammation-related gene expression and adult health outcomes. 

The study, titled “Hofbauer cell function in the term placenta associates with adult cardiovascular and depressive outcomes,” was published in Nature Communications. The researchers employed a rigorous and multi-faceted approach involving various molecular, genetic, and statistical techniques to investigate the impact of placental inflammation-related gene expression on adult health outcomes in non-pathogenic conditions. 

The team utilized cohort data from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study and the UK Biobank. RNA sequencing of 44 placental samples from GUSTO revealed an inflammation-related gene co-expression module enriched in Hofbauer cells. This particular module, known as the cyan module, showed high specificity to placental Hofbauer cells and was enriched with known inflammation-related genes.

To predict this module’s gene expression, the researchers developed a fetoplacental polygenic score (fetoplacental PGS). The fetoplacental PGS was significantly linked to 21 traits in a UK Biobank study, primarily associated with anthropometric or mental health traits. Notably, all anthropometric traits had a positive direction of effect, indicating an increased risk, while all traits within the mental health domain had a negative direction, suggesting a potential protective effect. 

However, the study did not find a correlation between the fetoplacental PGS and polygenic risk scores for depression or cardiovascular disease in the UK Biobank. This unexpected result raises questions about the role of the cyan module and its potential protective effect on these outcomes or suggests a more nuanced or indirect relationship that is not fully understood. 

Interestingly, a sex-dependent feature was identified, revealing a female-specific effect of cyan module genes on a reduced risk of suicidality. This finding adds complexity to the relationship between placental gene expression and mental health outcomes. 

The lack of correlation between traits associated with depression or cardiovascular disease outcomes could be attributed to genetic disparities between the GUSTO and UK Biobank cohorts. The placental biopsies were primarily conducted in individuals of Chinese, Malay, and Indian ethnicities in GUSTO, while the outcomes were derived from the more diverse population of the UK Biobank, covering 500,000 individuals across the United Kingdom.

This difference in population origin and diversity may influence the generalizability and applicability of the study’s findings. The research suggests that disruptions in Hofbauer cell function due to preterm birth or prenatal infections contribute to increased risk factors for depression and cardiovascular disease later in life.

However, the lack of direct correlations in outcomes raises intriguing questions about the role of the cyan module and the complexity of the relationship between placental gene expression and adult health outcomes.

The genetic disparities between cohorts highlight the need for further research to better understand these associations and their implications for diverse populations. Science, always welcoming a mystery, may uncover a more complete understanding as researchers continue to explore these intriguing findings. 

Journal Reference  

Eamon Fitzgerald et al, Hofbauer cell function in the term placenta associates with adult cardiovascular and depressive outcomes, Nature Communications (2023). DOI: 10.1038/s41467-023-42300-8.