Epigenetic Modification via H3K4me3 and H3K9ac in Human Placenta is Reduced After SARS-CoV-2 Infection During Pregnancy

Background/Objectives: Histone modifications play a key role in the regulation of gene transcription, with alterations in these modifications influencing trophoblast invasion and migration, crucial for placental development. Previously, we observed reduced trimethylated histone H3K4me3 and acetylated H3K9ac levels in the placentas of women with preeclampsia, associated with impaired transcriptional access. This study aims to investigate the impact of SARS-CoV-2 infection on histone modifications in placentas. Methods: Immunohistochemical Staining and Double-staining Immunofluorescence were performed on placentas of patients during after a SARS-CoV-2 infection during pregnancy as well as vaccinated and not vaccinated controls. Results: Our findings reveal that both H3K4me3 and H3K9ac are significantly reduced in placentas following SARS-CoV-2 infection during pregnancy, with more pronounced alterations observed compared to infections during birth. Additionally, vaccination did not exhibit a stronger effect than infection itself on histone modifications. Conclusions: Reduced H3K9ac and H3K4me3 suggest a more repressive chromatin state, likely silencing key placental genes through increased HDAC activity. These epigenetic changes may impair placental function and lead to pregnancy complications, underscoring the need for further research.