Association of elevated ACSL4 expression with impaired endometrial receptivity in endometriosis and restoration by ACSL4 inhibitor PRGL493

Xu L, Lei Xu, Hong Wei, Wei H, Wei Hong, Yun-Ju Shang, Shang Y, Yuhong Shang, Qing Yang, Yang Q
Journal of Reproductive Immunology · 2025 · vol. 171 , pp. 104630 · doi:10.1016/j.jri.2025.104630 · PMID:40763450 · W4412676075
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Elevated ACSL4 expression in endometriosis impairs endometrial receptivity, but treatment with ACSL4 inhibitor PRGL493 restores receptivity markers and ameliorates ultrastructural defects in both mouse models and human organoids.

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Abstract

This study investigated the role of ACSL4 in endometrial receptivity disorders in endometriosis (EMs) and evaluated PRGL493, an ACSL4 inhibitor, as a potential therapeutic target. Bioinformatic analysis identified ACSL4 as a potential key regulator among ferroptosis and receptivity-related genes. Clinical samples from EMs patients showed significantly higher endometrial ACSL4 expression and lower receptivity marker expression (αVβ3, OPN, HOXA10) compared to controls. In a mouse EMs model, PRGL493 treatment reduced lesion volume, decreased lipid peroxidation, increased pinopode formation, and improved expression of receptivity markers. Similarly, in human endometrial organoids from EMs patients, PRGL493 ameliorated ultrastructural abnormalities, including mitochondrial condensation, decreased secretory granules, and endoplasmic reticulum expansion, and restored receptivity marker expression to levels comparable to the control. These findings demonstrate that ACSL4 overexpression is associated with endometrial receptivity disorders in EMs and that ACSL4 overexpression is a key pathological feature linked to endometrial receptivity impairment in EMs. Targeting ACSL4 with PRGL493 ameliorates receptivity defects, suggesting its therapeutic potential for EMs-associated infertility.

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Condition tags

endometriosis

MeSH descriptors

Coenzyme A Ligases Coenzyme A Ligases Coenzyme A Ligases Coenzyme A Ligases Coenzyme A Ligases Coenzyme A Ligases Coenzyme A Ligases Coenzyme A Ligases Coenzyme A Ligases Coenzyme A Ligases Coenzyme A Ligases Coenzyme A Ligases Coenzyme A Ligases Coenzyme A Ligases Coenzyme A Ligases Coenzyme A Ligases Coenzyme A Ligases Coenzyme A Ligases Coenzyme A Ligases Coenzyme A Ligases

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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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