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

Meng Wang, Wang M, Yungai Xiang, Xiang Y, Zhang D, Dan Zhang, Xujing Geng, Geng X, Xiting Han, Han X, Peipei Guo, Guo P, Le Zhang, Zhang L, Li Tan, Li Jun Tan
Biology of reproduction · 2025 · vol. 113(4) , pp. 794–802 · doi:10.1093/biolre/ioaf126 · PMID:40518930 · W4411327719
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FKBP5 downregulation in adenomyosis endometrium increases endometrial stromal cell proliferation and migration while impairing decidualization by activating AKT signaling.

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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 insulin-like growth factor binding protein-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 protein kinase B/AKT (PKB/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.

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Condition tags

adenomyosis

MeSH descriptors

Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis Adenomyosis

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Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

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SciLite annotations

organisms 2
noordeloos 2009062 noordeloos 2009062
chemicals 1
oxygen

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