ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Molecular and Cellular Reproduction
This article is part of the Research TopicEditors’ Showcase 2025: Insights in Molecular and Cellular ReproductionView all 8 articles
Evidence for Nuclear KISS-1 Translocation and PI3K/AKT Signaling in Morphometric and Ultrastructural Analysis of Human Endometriosis
Provisionally accepted
- School of Medicine, Cumhuriyet University, Sivas, Türkiye
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Background: Endometriosis is a common estrogen-dependent disease marked by ectopic endometrial growth. Although the PI3K/AKT and kisspeptin pathways are known to regulate endometrial homeostasis, their interplay in disease progression remains unclear. This study investigated the relationship between nuclear Kisspeptin (KiSS-1) localization and PI3K/AKT pathway activity in endometriotic tissues, focusing on stage-specific cellular alterations. Methods: In this prospective study, control, eutopic and ectopic endometrial biopsies were collected from 27 women (18 controls, 9 with ovarian endometriosis). Histopathological assessments were performed using JB4 embedding, immunofluorescence, and transmission electron microscopy. Morphometric analyses were used to quantify structural alterations. Results: In both eutopic and ectopic endometrium from patients with endometriosis, PI3K and AKT expression levels were significantly increased, whereas KiSS-1 expression was reduced and showed nuclear localization in a subset of cells. TEM analysis revealed features consistent with cellular stress, including autophagy-related vesicles, mitochondrial structural disruption, and alterations in nuclear architecture. Morphometric evaluation demonstrated a fibrotic remodeling in ectopic tissue. Specifically, glandular volume decreased, while stromal matrix content increased (p<0.05). Conclusion: These findings suggest a mechanistic link between PI3K/AKT signaling and nuclear KiSS-1 translocation as an adaptive response to chronic hypoxia and inflammation in endometrial cells. This interaction may regulate survival, proliferation, and fibrotic remodeling processes characteristic of endometriosis. This integrated ultrastructural and molecular analysis provides novel insights into the pathophysiological role of nuclear KiSS-1 and its potential as a diagnostic and therapeutic target in endometriosis.
Keywords: Autophagy, Endometriosis, Intranuclear inclusions, JB-4 embedding technique, Kisspeptin, Mitochondrial degeneration, PI3K/Akt signaling pathway, Stromal remodelling
Received: 08 May 2025; Accepted: 08 Dec 2025.
Copyright: © 2025 Hamutoğlu, Kaloğlu, Bulut and Yıldız. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Celal Kaloğlu
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