The Immuno-Endocrine Feedback Loop for Endometrial Decidualization in Endometriosis

Journal of Reproductive Medicine Gynaecology & Obstetrics Category: Medical Type: Commentary Reproductive Medical Center, The First Affiliated Hospital Of Guangxi Medical University, Nanning, Guangxi, China Tel:+86 7715311689, Fax:+86- 7715356816 Email:[email protected] Received Date: Jan 14, 2026 Accepted Date: Jan 27, 2026 Published Date: Feb 03, 2026 The intricate dialogue between endocrine signaling and immune-inflammatory homeostasis at the maternal-fetal interface remains one of the most complex frontiers in reproductive biology. In the recent review titled “Hormonal imbalance-mediated immune inflammation in endometrial decidualization disorder,” Yu et al., provide a masterly synthesis of how the disruption of this dialogue underpins the pathophysiology of endometriosis-associated infertility [1]. By moving beyond a reductionist view of hormonal deficiency, the authors delineate a self-perpetuating cycle where estrogen dominance and progesterone resistance act as both the drivers and the consequence of a chronic inflammatory state. At the molecular core of this disorder lies a profound breakdown in homeostatic feedback loops. The authors highlight the critical role of the Estrogen-Prostaglandin E2 (PGE2) axis, where the local hyperestrogenism stimulates COX-2 expression, leading to elevated PGE2 levels [2]. This, in turn, acts as a potent stimulus for aromatase activity, further escalating local estrogen production. This feedforward mechanism is not merely an endocrine aberration; it is a primary driver of immune reprogramming. Through the activation of the NF-κB signaling pathway, this environment facilitates the transcriptional silencing of the progesterone receptor B (PR-B) isoform, effectively rendering the endometrium “blind” to the pro-gestational signals required for decidual transformation [3]. The immunological consequences of this hormonal landscape are equally significant. Yu et al., describe a shift in the endometrial microenvironment from receptive tolerance to inflammatory activation. The review synthesize evidence on how the failure of progesterone signaling—compounded by estrogen excess—shifts the maternal-fetal interface toward a pro-inflammatory state. This is characterized by the dominance of M1 macrophages over M2, a Th1-biased helper T-cell response, and the accumulation of cytotoxic uterine Natural Killer cells. These shifts collectively disrupted the immune tolerance required for successful decidualization, providing a clear explanation for why standard assisted reproductive technologies often come out with lower success rates in patients with severe endometriosis [4]. From a clinical perspective, this synthesis offers a compelling rationale for multi- modal therapeutic strategies. The authors identify promising strategies such as the use of Dienogest —not merely as a hormonal suppressant, but as a dual-action agent that restores the PR-B/PR-α ratio while inhibiting aromatase-mediated inflammation [5]. Furthermore, the discussion of emerging technologies, specifically single-cell RNA sequencing and endometrial organoids, signals a transition toward precision medicine. These tools allow for the mapping of individual immune and hormonal signatures, potentially dictating personalized fertility treatments in the future [6]. In summary, Yu et al., have successfully framed endometriosis-associated infertility as a systemic failure of the immuno-endocrine dialogue. By integrating the disparate threads of endocrinology, immunology, and molecular biology into a unified narrative, this work provides a vital framework for understanding the “endometrial factor.” This review stands as an essential resource for researchers and clinicians seeking to translate complex molecular interactions into improved reproductive outcomes. - Yu J, Qin R, Huang P, Hang F, Guo Y, et al. (2025) Hormonal imbalance-mediated immune inflammation in endometrial decidualization disorder. - Ota H, Igarashi S, Sasaki M, Tanaka T (2001) Distribution of cyclooxygenase-2 in eutopic and ectopic endometrium in endometriosis and adenomyosis. Hum Reprod 16: 561-566. - Zhao W, Wang Y, Liu J, Yang Q, Zhang S, et al. (2023) Progesterone Activates the Histone Lactylation-Hif1α-glycolysis Feedback Loop to Promote Decidualization. Endocrinology 165: bqad169. - Önalan G, Tohma YA, Zeynelo?lu HB (2018) Effect of etanercept on the success of assisted reproductive technology in patients with endometrioma. Gynecol Obstet Invest 83: 358-364. - Wang C, Zhao M, Zhang WQ, Huang MY, Zhu C, et al. (2020) Comparative analysis of mouse decidualization models at the molecular level. Genes (Basel) 11: 935. - Liu S, Li X, Gu Z, Wu J, Jia S, et al. (2025) Single-cell and spatial transcriptomic profiling revealed niche interactions sustaining growth of endometriotic lesions. Cell Genom 5: 100737. Citation: Liao M, Qin A (2026) The Immuno-Endocrine Feedback Loop for Endometrial Decidualization in Endometriosis. HSOA J Reprod Med Gynaecol Obstet 11: 211. Copyright: © 2026 Ming Liao, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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