Reduced endometrial expression of histone deacetylase 3 in women with adenomyosis who complained of heavy menstrual bleeding

Lesional fibrosis results in reduced endometrial HDAC3 expression and subsequent disruption in NF-κB signalling and inflammation, leading to adenomyosis-associated HMB.

Compared with controls, the endometrial staining of HDAC3 was significantly lower in women with adenomyosis-associated HMB, concomitant with a greater extent of fibrosis. The stiffness of lesions and neighbouring EMI was significantly higher in the EXB group compared with the MHB group, as was the extent of fibrosis in lesions, their neighboring EMI and endometrium. Expression of HDAC3 was reduced significantly when endometrial epithelial cells were cultured in stiff substrates. Suppression of HDAC3 abrogated the activation and signalling of NF-κB. Mice with induced adenomyosis exhibited reduced Hdac3 staining and elevated fibrosis in endometrium, concomitant with disrupted endometrial repair and more bleeding. Hdac3 inhibition resulted in botched inflammation and increased bleeding. Conclusions: Lesional fibrosis results in reduced endometrial HDAC3 expression and subsequent disruption in NF-κB signalling and inflammation, leading to adenomyosis-associated HMB.