P-430 The placentation defects are associated with the abnormal proangiogenic signaling of Hofbauer cells driven by advanced maternal age
Authors: Wang H , Zhuo S , Chen X 
Published: July 2024

Abstract

Study question
Does the abnormality of Hofbauer cells, a subtype of macrophages, in the placental villi cause abnormal placental development in advanced pregnant women?

Summary answer
Maternal age has a significant impact on the proangiogenic capacity of Hofbauer cells in the placental villi.

What is known already
Hofbauer cells, a population of macrophages that existed in the placental villi, are known to be related to the transmission of pathogens in the materno-fetal interface. In addition, it has been known that Hofbauer cells can express some cytokines, such as VEGF-A and IL-8, being able to promote angiogenesis. Advanced maternal age has a higher probability to cause placental abnormalities. Whether this is related to alterations in the pro-angiogenic capacity of Hofbauer cells is not clear.

Study design, size, duration
To investigate the relationship between the angiogenic capacity of Hofbauer cells and maternal age, we compared the difference in strength of proangiogenetic signaling of Hofbauer cells between advanced maternal age and young maternal age in the single cell level, and identified the genes in Hofbauer cells that are most affected by advanced maternal age, which was further validated by immunofluorescence and in vitro tube formation assay.

Participants/materials, setting, methods
We collected six placental tissues (3 advanced maternal age and 3 young maternal age) across mid- and later-gestational trimesters and performed scRNA-seq, cytometry analysis, and tube formation assay. In addition, we performed immunofluorescence to validate the findings in the scRNA-seq data.

Main results and the role of chance
We report that the number of macrophages in the placenta of advanced maternal age is significantly lower than in the placenta of younger counterpart, and Hofbauer cell, a fetal-derived macrophage within the placental villi, has obvious down-regulation of proangiogenic signal in advanced maternal age, which is closely associated with the occurrence of placentation defects. Since some key angiogenic factors, such as HIF1A, appear to be more important in the early stages of placental development, placental malformations associated with them may occur more frequently in the early stage of gestation.

Limitations, reasons for caution
Although we tentatively identified the effect of advanced pregnancy on the angiogenesis-promoting capacity of Hofbauer cells, it is unclear about the dynamic course of angiogenesis signaling of Hofbauer cells throughout the whole gestation. It is necessary to understand the effects of Hofbauer cells on placental development at different gestational trimesters.

Wider implications of the findings
The investigations of this study into the proangiogenesis of Hofbauer cells are useful to develop potential placental interventions to ameliorate poor birth outcomes. In addition, it lays the foundation for further understanding the underlying molecular mechanism regulating the proangiogenic function of Hofbauer cells in detail.

Trial registration number
not applicable