Increased levels of DNA methyltransferases in the placentas of women affected by Placenta Accreta Spectrum lead to aberrant DNA methylation patterns

Abstract

Placenta Accreta Spectrum (PAS) is a serious placental abnormality assosiated with significant maternal death during pregnancy. Due to its invasive characteristics resembling tumor growth, PAS is often associated with tumor-related proteins. While DNA methylation is known to regulate genes involved in development, its potential role in the development of PAS remains unclear. The aim of our study was to investigate the impact of PAS on DNA methylation and DNA methyltransferases (DNMTs). The groups were categorized into three groups: vaginal birth, cesarean delivery, and cesarean delivery with PAS. To measure DNMT protein levels in placental tissue, we employed immunohistochemistry (IHC) and Western blot (WB) techniques. Global DNA methylation levels were assessed using 5-methylcytosine staining. We found that DNMT1, DNMT3A and DNMT3L levels were significantly increased in the placentas of PAS group compared to control counterparts in both WB and IHC analysis. Compatible with DNMTs expressions, global DNA methylation levels were found to be significantly higher in placentas from women with PAS compared to controls. Our results suggest that significant alterations in DNMTs expressions and global DNA methylation within placentas may contribute to the development of Placenta Accreta Spectrum (PAS). To elucidate the precise molecular mechanisms underlying these changes and their role in PAS pathogenesis, further research required.