Characterising placental macrophages and inflammation in placental pathology

• Main Author: Sharps, Megan
• Format: Dissertation
• Language: English
• Published: University of Manchester 2022

Placental dysfunction underlies multiple pregnancy complications, including fetal growth restriction and stillbirth. Recently, there has been growing interest in the role of inflammation in these conditions. Placental macrophages (Hofbauer cells) remove debris from apoptotic cells, produce growth factors to aid vasculogenesis and protect against infections. Macrophages can be either inflammatory or anti-inflammatory. This programme of research investigated the hypothesis that there will be altered numbers of Hofbauer cells in placentas in pregnancy complications alongside changes in the inflammatory profile and phenotype of the macrophages. Using imaging mass cytometry to assess markers of Hofbauer cell phenotype demonstrated they remain M2 in phenotype across gestation; with homogenous expression of CD163 and CD206 but heterogeneous expression of CD209. Cell clusters containing Hofbauer cells neighbour vascular endothelial cells. Using this novel technology, these data corroborate previous research performed using traditional approaches such as immunohistochemistry. In infants with a decreased growth rate, there were significantly more placental macrophages, accompanied by a pro-inflammatory shift in both the placenta and the maternal environment. These changes were not observed in infants with ≤3rd individualised birthweight centile. Placental villous explant models to mimic placental dysfunction were used to assess whether the insults affected macrophage number and phenotype. There was a significant increase in the number of macrophages in the villous explants cultured in a hypoxic environment. There was no difference in the number of macrophages following LPS treatment, but there was the presence of pro-inflammatory macrophages, which were not observed in the explants in cultured in control conditions. During the COVID-19 pandemic, it was unclear if maternal SARS-CoV-2 infection would have effects on the placenta. A systematic review was conducted; in the included studies, there was little evidence of vertical transmission, but there was an increase in the presence of both maternal and fetal vascular malperfusion. Analysis of placentas of women who had current and prior SARS-CoV-2 infection found there were significantly more macrophages in the placentas of women who had recovered from COVID-19, but without changes in the number of T or B cells. None of the placentas tested positive for the SARS-CoV-2 and there was no associated placental histopathological changes. This research demonstrates that the number of placental macrophages are increased in certain conditions with placental dysfunction; alongside a switch to a pro-inflammatory placental environment. It remains unclear why this increase occurs and whether macrophages are contributing to or causing the inflammation. The role of placental inflammation and whether this offers a novel therapeutic pathway to modify placental dysfunction merits further investigation.