IJMS, Vol. 19, Pages 4061: Histone H3 lysine 9 acetylation is downregulated in GDM Placentas and Calcitriol supplementation enhanced this effect (International Journal of Molecular Sciences)

Despite the ever-rising incidence of Gestational Diabetes Mellitus (GDM) and its implications for long-term health of mothers and offspring, the underlying molecular mechanisms remain to be elucidated. To contribute to this, the present study`s objectives are to conduct a sex-specific analysis of active histone modifications in placentas affected by GDM and to investigate the effect of calcitriol on trophoblast cell`s transcriptional status. The expression of Histone H3 lysine 9 acetylation (H3K9ac) and Histone H3 lysine 4 trimethylation (H3K4me3) was evaluated in 40 control and 40 GDM (20 male and 20 female each) placentas using immunohistochemistry and immunofluorescence. The choriocarcinoma cell line BeWo and primary human villous trophoblast cells were treated with calcitriol (48 h). Thereafter, western blots were used to quantify concentrations of H3K9ac and the transcription factor FOXO1. H3K9ac expression was downregulated in GDM placentas, while H3K4me3 expression was not significantly different. Cell culture experiments showed a slight downregulation of H3K9ac after calcitriol stimulation at the highest concentration. FOXO1 expression showed a dose-dependent increase. Our data supports previous research suggesting that epigenetic dysregulations play a key role in gestational diabetes mellitus. Insufficient transcriptional activity may be part of its pathophysiology and this cannot be rescued by calcitriol.