Examining the Effects of Gestational Physical Activity and Hofbauer Cell Polarization on Angiogenic Factors.

While gestational physical activity (PA) has demonstrated health benefits for both birthing parent and fetus, the mechanisms still need to be fully understood. Placental macrophages, or Hofbauer cells (HBCs), comprise a heterogenous population containing inflammatory (CD206-) and anti-inflammatory (CD206+) phenotypes. Similar to other tissue-resident macrophages (TRMs), HBCs are potential mediators of angiogenesis due to their secretion of both pro- and anti-angiogenic factors, including FGF2, VEGF, and SPRY2. While PA is associated with an increase in the proportion of VEGF- and FGF2-producing CD206+ macrophages in other tissues, the phenotypes producing FGF2, VEGF, and SPRY2 in the placenta and the associated relationships with gestational PA have not been studied. Using accelerometry, pregnant participants were classified as physically active or inactive in mid- and late-gestation. Term placenta tissue was collected at delivery and used for Western blotting and immunofluorescence to examine the protein expression of FGF2 and SPRY2, and to localize FGF2 in histological samples, respectively. Primary cultures of HBCs were used to examine the phenotypic differences in FGF2, SPRY2, and VEGF production. While no differences in the placental expression of SPRY2, total FGF2, or high-molecular-weight FGF2 were observed based on PA status, active individuals had significantly reduced levels of low-molecular-weight FGF2. Additionally, HBCs of all polarizations produce VEGF, FGF2, and SPRY2, and can form intercellular junctions and multinucleated giant cells. These findings suggest a possible relationship between PA and HBC-driven angiogenesis, providing an avenue for future exploration.

Characterization of Hofbauer cell polarization and VEGF localization in human term placenta from active and inactive pregnant individuals.

Physical activity (PA) during pregnancy is associated with parental and fetal health benefits; however, the mechanisms through which these benefits arise are yet to be fully understood. In healthy pregnancies Hofbauer cells (HBCs) comprise a heterogenous population containing CD206+ and CD206- phenotypes. In healthy pregnancies, CD206+ represent the majority, while dysregulations have been associated with pathological conditions. HBCs have also been identified as potential drivers of angiogenesis. As PA induces changes in macrophage polarization in non-pregnant populations, this novel study examined the relationship between PA and HBC polarization and to identify which HBC phenotypes express VEGF. Participants were classified as active or inactive, and immunofluorescence cell-labelling was used to quantify total HBCs, CD206+ HBCs, and the proportion of total HBCs expressing CD206. Immunofluorescent colocalization assessed which phenotypes expressed VEGF. Protein and mRNA expression of CD68 and CD206 were measured in term placenta tissue using Western blot and RT-qPCR, respectively. Both CD206+ and CD206- HBCs expressed VEGF. The proportion of CD206+ HBCs was elevated in active individuals; however, CD206 protein expression was observed to be lower in active participants. Combined with a lack of significant differences in CD206 mRNA levels, these findings suggest potential PA-mediated responses in HBC polarization and CD206 translational regulation.