Hormonal signaling orchestrates the growth, differentiation, and regeneration of female reproductive tissues, modulating the tissue microenvironment, inflammation, stromal activity, and extracellular matrix (ECM). These mechanisms support the physiological remodeling of the ovary, uterus, cervix, and uterine tubes, besides the changes associated with ovarian aging and menopause, where mild and controlled fibrosis occurs. However, dysregulation of these endocrine signals or their interaction with the tissue environment can induce aberrant remodeling, characterized by chronic inflammation, persistent stromal activation, and excessive ECM accumulation. Emerging evidence shows that estrogens and progestogens regulate fibroblast activation, ECM deposition, and cytokine networks within the ovary and endometrium. Pathological fibrosis disrupts tissue architecture and function, contributing to pain, infertility, and therapeutic resistance.

Understanding the mechanistic connections between endocrine dysregulation, fibrotic remodeling, and oncogenic transformation is crucial for unraveling the mechanisms that balance regeneration and reproductive function. This knowledge opens new avenues for therapeutic intervention and disease prevention. This Research Topic aims to integrate current knowledge and stimulate interdisciplinary research on how endocrine factors modulate the remodeling of reproductive tissues across health, aging, and disease. We invite exploration into how endocrine signaling modulates tissue remodeling in female reproductive organs, encompassing basic, translational, and clinical studies. We also encourage submissions that can guide the development of antifibrotic, anti-inflammatory, and regenerative strategies aimed at preserving or restoring the health of the female reproductive system.

We welcome contributions addressing, among others, the following themes in female reproductive tissues:

• Mechanisms by which estrogens, progesterone, and selective hormonal modulators (e.g., estetrol, SERMs, progestins) influence fibroblast activation, ECM synthesis, and tissue stiffness.

• Interactions between endocrine pathways (ER, PR, TGF-β, PI3K/AKT, Hippo, etc.) and fibrogenic or inflammatory signaling networks.

• The role of ECM remodeling and fibrosis in ovarian aging, menopause, and gynecologic pathologies (including endometriosis, endometritis, adenomyosis, leiomyomas, endometrial hyperplasia, gynecologic cancers, and PCOS, among others).

• Novel antifibrotic, anti-inflammatory, or regenerative strategies targeting key endocrine pathways involved in reproductive health.

• Biomarkers and imaging tools to monitor endocrine-mediated changes in tissue architecture.

• Comparative and translational models of endocrine-induced tissue remodeling (e.g., animal models, organoids, biomaterials, or ex vivo systems).

Original research articles, Reviews, and Mini Reviews, among others, are accepted.

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Endocrine Dysregulation and Tissue Microenvironment Remodeling in Female Reproductive Health