The downregulation of FKBP5 contributes to the pathogenesis of adenomyosis and is associated with impaired endometrial receptivity†.

Abstract

Adenomyosis is characterized by the infiltration of endometrial glands and stroma into the myometrium which affects about 35% women at reproductive age. Women affected by adenomyosis always experience issues such as defective decidualization, reduced endometrial receptivity, disrupted embryo-maternal communication, and challenges with implantation. However, the underlying mechanism remains obscure. We analyzed three gene expression profiling datasets (GSE244236, GSE190580 and GSE157718) and identified that FKBP5 was significantly reduced in endometrium from patients with adenomyosis. Primary endometrial stromal cells (ESCs) from patients had increased proliferation, reduced apoptosis and elevated migration capacity. Knockdown FKBP5 in ESCs upregulated proliferation, repressed apoptosis, and impaired the secretion of prolactin and IGFBP-1 during in vitro decidualization. Meanwhile, repressing FKBP5 in ESCs promoted oxygen consumption rate, extracellular acidification rate, and ATP production. Mechanically, knockdown FKBP5 in ESCs activated AKT signaling by promoting its phosphorylation at Ser-473. FKBP5 was downregulated in patients with adenomyosis which contributed to impaired ESCs function and the process of decidualization providing a candidate target for adenomyosis treatment.