Balancing Decidualization, Autophagy, and Cellular Senescence for Reproductive Success in Endometriosis Biology

Hiroshi Shigetomi, Miki Nishio, Motohide Nishio, Mai Umetani, Shogo Imanaka, Hiratsugu Hashimoto, Hiroshi Kobayashi
International journal of molecular sciences · 2025 · vol. 26(18) , pp. 9125 · doi:10.3390/ijms26189125 · PMID:41009686 · W4414308503
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⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

This review explores how disrupted decidualization, autophagy, and cellular senescence, particularly the p53-AMPK-mTOR axis, contribute to endometriosis progression and infertility.

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Abstract

Endometriosis is a chronic disease characterized by the ectopic presence of endometrial cells that evade apoptosis and survive and proliferate under harsh environmental conditions. It is closely associated with infertility and pregnancy-related complications. This review focuses on the molecular pathophysiology of endometriosis, particularly the disruption of the p53-AMPK-mTOR signaling axis, and highlights the dysregulation of decidualization and cellular senescence, incorporating recent findings in reproductive physiology. A comprehensive literature search was conducted using PubMed and Google Scholar without temporal restrictions. Endometriotic cells adapt to the hostile peritoneal environment through resistance to apoptosis and alterations in autophagy. In the early stages, autophagy activation may promote cell survival; however, as the disease progresses, autophagic activity tends to decline. Aberrant activation of mTOR signaling is implicated in this process, contributing to the suppression of autophagy, impaired decidualization, and promotion of cellular senescence, ultimately facilitating lesion progression and infertility. Indeed, in the eutopic endometrium of patients with endometriosis, progesterone resistance, elevated inflammatory cytokines, and epigenetic abnormalities are known to reduce endometrial receptivity. Moreover, suppression of autophagy leads to excessive cellular senescence and secretion of the senescence-associated secretory phenotype (SASP), thereby interfering with proper decidualization. Maintaining an appropriate balance between decidualization and cellular senescence is essential for reproductive function. Future development of therapeutic strategies targeting these processes is expected to help overcome infertility associated with endometriosis.

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Condition tags

mesh:D004715endometriosisinfertility

MeSH descriptors

Autophagy Autophagy Autophagy Autophagy Autophagy Autophagy Autophagy Autophagy Autophagy Cellular Senescence Cellular Senescence Cellular Senescence Cellular Senescence Cellular Senescence Cellular Senescence Cellular Senescence Cellular Senescence Cellular Senescence Decidua Decidua

Citation neighborhood

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.

References (100)

Source provenance

europepmc
last seen: 2026-06-04T01:30:01.192114+00:00
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