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Molecular Insights in Women’s Health: Advances in Gynecological Disease Mechanisms and Therapeutics

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 30 November 2026 | Viewed by 5454

Editor

Dr. Tsung-Hsuan Lai

E-Mail Website
Guest Editor
Cathay General Hospital, School of Medicine, Fu Jen Catholic University, Taipei, Taiwan
Interests: assisted reproductive technologies; female infertility; gynecological minimal invasive surgery; polycystic ovarian syndrome; endometriosis; male infertility; robotic surgery in reproduction and gynecology; AI application in obstetrics; gynecology and infertility; prenatal diagnosis; menopause

Special Issue Information

Dear Colleagues, 

Women’s health represents a cornerstone of medical science, with gynecological disorders significantly affecting quality of life, fertility, and long-term well-being. Advances in molecular biology, diagnostics, and therapeutic strategies have opened new opportunities for early detection, individualized treatment, and preventive care in gynecological diseases.

This Special Issue “Molecular Insights in Women’s Health: Advances in Gynecological Disease Mechanisms and Therapeutics” aims to provide a multidisciplinary platform for high-quality original research articles and comprehensive reviews. This Special Issue will focus on the molecular researches of gynecological diseases and their translation into diagnostics and therapeutics. We welcome original research and reviews addressing:
- Molecular mechanisms and signaling pathways in gynecological conditions such as polycystic ovary syndrome, endometriosis, infertility, menopause, and gynecological cancers.
- Biomarkers and genetic/epigenetic signatures for disease diagnosis, prognosis, and personalized treatment.
- Molecular endocrinology of reproductive function and pregnancy, including novel insights into hormone signaling and regulation.
- Molecular aspects of fertility preservation and regenerative medicine.
- Translational approaches linking molecular discoveries to clinical applications in gynecology and reproductive medicine.
- Emerging molecular technologies including AI-driven molecular diagnostics, omics-based profiling, and novel therapeutic targets.

By emphasizing the molecular perspective, this Special Issue aims to bridge laboratory discoveries and clinical applications, fostering innovations that will improve women’s health outcomes globally.

We look forward to your valuable contributions.

Dr. Tsung-Hsuan Lai
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • ART and IVF
  • prenatal diagnosis
  • infertility
  • minimally invasive surgery
  • robotic surgery
  • PCOS
  • endometriosis
  • menopause
  • AI

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Published Papers (6 papers)

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Research

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16 pages, 11346 KB  
Article
Differential Effects of Mesenchymal Stem Cell- and Natural Killer Cell-Derived Extracellular Vesicles on Cisplatin Responsiveness in Endometrial Cancer Cells
by Ren-Jun Hsu, Cheng-Shuo Huang, Ming-Kung Yeh, Zheng-Zong Lai, Cheng-Ping Yu, Jar-Yi Ho and Fung-Wei Chang
Int. J. Mol. Sci. 2026, 27(13), 5842; https://doi.org/10.3390/ijms27135842 - 28 Jun 2026
Viewed by 468
Abstract
Cisplatin (cis-diamminedichloroplatinum(II) [DDP]) is a key chemotherapeutic agent for advanced endometrial cancer; however, chemoresistance substantially limits its clinical benefit. Extracellular vesicles (EVs) mediate intercellular communication and influence tumour cell behaviour and therapeutic response. We investigated whether mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) and [...] Read more.
Cisplatin (cis-diamminedichloroplatinum(II) [DDP]) is a key chemotherapeutic agent for advanced endometrial cancer; however, chemoresistance substantially limits its clinical benefit. Extracellular vesicles (EVs) mediate intercellular communication and influence tumour cell behaviour and therapeutic response. We investigated whether mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) and natural killer cell-derived extracellular vesicles (NK-EVs) modulate cisplatin responsiveness in endometrial cancer cells (RL95-2 and HEC-1A). MSC-EVs and NK-EVs were isolated and characterised using nanoparticle tracking analysis, scanning electron microscopy, and EV marker profiling. MSC-EVs and NK-EVs reduced RL95-2 and HEC-1A cell viability in a dose-dependent manner, with MSC-EVs exhibiting substantial effects at lower particle concentrations. In a cisplatin-resistant HEC-1A (HEC-1A DDP-R) model, MSC-EVs were associated with greater reductions in cell viability under cisplatin treatment conditions, whereas NK-EVs showed comparatively modest effects. Mechanistic analyses demonstrated altered expression of apoptosis- and cell cycle–related proteins, including increased cleaved poly(ADP-ribose) polymerase and cleaved caspase-3 levels and reduced cyclin A and cyclin D1 expression following MSC-EV treatment. Annexin V-fluorescein isothiocyanate/propidium iodide flow cytometry demonstrated increased apoptotic cell populations after MSC-EV treatment, with MSC-EV + DDP co-treatment resulting in the highest apoptotic fraction in chemoresistant HEC-1A cells. Collectively, these findings indicate that MSC-EVs are associated with altered cellular responses to cisplatin in chemoresistant endometrial cancer cells, accompanied by changes in apoptosis-related protein expression, apoptotic cell populations, and cell-cycle regulators. Further investigation is required to determine their mechanistic role and therapeutic potential in overcoming chemoresistance. Full article
(This article belongs to the Special Issue Molecular Insights in Women’s Health: Advances in Gynecological Disease Mechanisms and Therapeutics)
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15 pages, 2759 KB  
Article
Primed Avian Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Restore Granulosa Cell Homeostasis in a CTX-Induced POI-like Dysfunction Model Under Human Menopausal Gonadotropin Stimulation
by Hsiang-Chun Dong, Kuo-Min Su, Chi-Kang Lin, Hui-Rong Cheng, Chih-Hsiang Yin and Fung-Wei Chang
Int. J. Mol. Sci. 2026, 27(11), 4934; https://doi.org/10.3390/ijms27114934 - 29 May 2026
Viewed by 549
Abstract
Premature ovarian insufficiency (POI) is a heterogeneous disorder, and cyclophosphamide (CTX)-induced ovarian injury represents an acquired POI-like condition rather than the full clinical spectrum of POI. In this study, CTX was used to establish a granulosa cell dysfunction model to evaluate whether primed [...] Read more.
Premature ovarian insufficiency (POI) is a heterogeneous disorder, and cyclophosphamide (CTX)-induced ovarian injury represents an acquired POI-like condition rather than the full clinical spectrum of POI. In this study, CTX was used to establish a granulosa cell dysfunction model to evaluate whether primed avian mesenchymal stem cell-derived small extracellular vesicles (primed AMSC-sEVs) could restore granulosa cell homeostasis under human menopausal gonadotropin (hMG) stimulation, a clinically relevant gonadotropin context used in ovarian stimulation. Human granulosa cells were exposed to CTX and subsequently treated with hMG, naïve AMSC-sEVs, or primed AMSC-sEVs. Cell viability, mitochondrial membrane potential, AMH and FSHR expression, and hormone secretion were examined. CTX reduced cell viability, mitochondrial membrane potential, AMH and FSHR expression, and AMH/estradiol secretion, confirming the establishment of a POI-like granulosa cell dysfunction state. hMG partially restored selected functional markers but showed limited effects on cell viability and mitochondrial recovery. In contrast, primed AMSC-sEVs markedly restored granulosa cell viability, mitochondrial membrane potential, AMH and FSHR expression, and endocrine output, with stronger effects than naïve AMSC-sEVs. Co-treatment with hMG did not consistently enhance the restorative effects of primed AMSC-sEVs beyond those achieved by primed AMSC-sEVs alone. These findings indicate that primed AMSC-sEVs primarily act by restoring granulosa cell and mitochondrial homeostasis, thereby supporting the cellular competence required for gonadotropin responsiveness in an acquired POI-like condition. Full article
(This article belongs to the Special Issue Molecular Insights in Women’s Health: Advances in Gynecological Disease Mechanisms and Therapeutics)
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25 pages, 2277 KB  
Article
Exosome-Enriched Hub Gene Networks Identify Diagnostic Biomarkers and Repurposable Therapeutic Targets in Endometriosis
by Meng-Hsiu Tsai, Shao-Ping Weng, Li-Jen Su and Tsung-Hsuan Lai
Int. J. Mol. Sci. 2026, 27(6), 2572; https://doi.org/10.3390/ijms27062572 - 11 Mar 2026
Viewed by 1253
Abstract
Endometriosis is a heterogeneous chronic inflammatory disorder associated with substantial diagnostic delay and limited therapeutic options, highlighting the need of robust non-invasive biomarkers and actionable molecular targets to complement existing low-sensitivity tests. To identify conserved pathogenic mechanisms with translational potential, here, we uniformly [...] Read more.
Endometriosis is a heterogeneous chronic inflammatory disorder associated with substantial diagnostic delay and limited therapeutic options, highlighting the need of robust non-invasive biomarkers and actionable molecular targets to complement existing low-sensitivity tests. To identify conserved pathogenic mechanisms with translational potential, here, we uniformly reprocessed three independent the Gene Expression Omnibus (GEO) microarray cohorts (GSE7305, GSE25628, and GSE11691) and applied a strict, directionally consistent intersection strategy to identify conserved transcriptional signals. We identified 262 consensus differentially expressed genes enriched for immunity/inflammation, cell adhesion and migration, and angiogenesis, consistent with key biological hallmarks of lesion establishment and persistence. Protein–protein interaction topology prioritized 11 highly connected hub genes (VCAM1, CCL2, MCAM, CD14, CD24, FGFR1, SIRPA, CSF1R, S100A9, S100A8, and LY96) that likely act as an integrated immune-adhesion-angiogenesis axis. Notably, 63/262 (24%) of the consensus genes were annotated to the extracellular exosome compartment, supporting their translational relevance as liquid-biopsy candidates. Finally, connectivity mapping using the LINCS L1000 framework nominated small-molecule perturbagens predicted to reverse the endometriosis-associated signature, providing a rational starting point for drug-repurposing experiments. In conclusion, this study elucidates a conserved immune–adhesion–angiogenesis axis driven by an 11-gene hub network in endometriosis. These core regulators represent promising candidates for the development of non-invasive liquid biopsies and precision, non-hormonal therapeutics. Full article
(This article belongs to the Special Issue Molecular Insights in Women’s Health: Advances in Gynecological Disease Mechanisms and Therapeutics)
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Review

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20 pages, 2088 KB  
Review
Technological Advances of Cryopreservation in Ovarian Tissue for Female Children: Exploring the Molecular Insights and Mechanisms
by Hsin-Hung Wu
Int. J. Mol. Sci. 2026, 27(12), 5186; https://doi.org/10.3390/ijms27125186 - 8 Jun 2026
Viewed by 687
Abstract
Ovarian tissue cryopreservation (OTC) has emerged as the only viable fertility preservation strategy for prepubertal girls and adolescent cancer patients facing gonadotoxic treatments. While OTC has transitioned from an experimental procedure to an established clinical practice, the functional longevity of transplanted grafts remains [...] Read more.
Ovarian tissue cryopreservation (OTC) has emerged as the only viable fertility preservation strategy for prepubertal girls and adolescent cancer patients facing gonadotoxic treatments. While OTC has transitioned from an experimental procedure to an established clinical practice, the functional longevity of transplanted grafts remains limited by massive follicle depletion. This review synthesizes recent technological advances in OTC for female children, with a particular focus on the underlying molecular mechanisms and innovative protective strategies. We systematically evaluate pre-cryopreservation assessments, surgical harvesting techniques such as medulla-sparing biopsies, and the comparative efficacy of slow freezing versus vitrification in preserving stromal and follicular integrity. Central to this discussion are the molecular drivers of post-transplantation injury, including ischemia–reperfusion-induced oxidative stress and the iatrogenic over-activation of the PI3K/Akt/mTOR signaling pathway, which leads to follicular “burnout.” Furthermore, we explore targeted pharmacological interventions, such as the dual-drug application of VEGFA and rapamycin, alongside emerging bioengineering frontiers including decellularized extracellular matrix scaffolds and 3D-printed bioprosthetic ovaries. Clinical outcomes are also summarized, highlighting high rates of endocrine recovery (~95%) and promising live birth rates (~28%), predominantly through natural conception. By integrating deep molecular insights with advanced tissue engineering, this review provides a comprehensive framework for optimizing long-term fertility restoration and improving the quality of survivorship for young female cancer survivors. Full article
(This article belongs to the Special Issue Molecular Insights in Women’s Health: Advances in Gynecological Disease Mechanisms and Therapeutics)
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18 pages, 3218 KB  
Review
Adiponectin and Polycystic Ovary Syndrome in Adolescent Girls: A Systematic Review and Meta-Analysis
by Sheran P. W. Fernando and Prakash V. A. K. Ramdass
Int. J. Mol. Sci. 2026, 27(9), 3950; https://doi.org/10.3390/ijms27093950 - 29 Apr 2026
Cited by 1 | Viewed by 624
Abstract
Polycystic ovary syndrome (PCOS) is a prevalent endocrine–metabolic disorder affecting 5.5–11.5% of women of reproductive age. While reduced adiponectin levels have been consistently demonstrated in adult women with PCOS, findings in adolescents remain less clearly defined. A systematic review and meta-analysis was conducted [...] Read more.
Polycystic ovary syndrome (PCOS) is a prevalent endocrine–metabolic disorder affecting 5.5–11.5% of women of reproductive age. While reduced adiponectin levels have been consistently demonstrated in adult women with PCOS, findings in adolescents remain less clearly defined. A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines. PubMed, Embase, Scopus, and Google Scholar were searched from inception to 31 October 2025. Observational studies comparing adiponectin levels in post-pubertal adolescents with PCOS and controls were included. Data were pooled using random-effects meta-analysis in RStudio, with subgroup, sensitivity, heterogeneity, and publication bias analyses conducted. Eighteen studies comprising 1590 participants were analyzed. The pooled analysis demonstrated significantly lower adiponectin levels in adolescents with PCOS compared to controls (mean difference [MD]: −3.19 µg/mL; 95% CI: −4.90 to −1.49; p = 0.0010), with substantial heterogeneity (I2 > 90%). Subgroup analyses by diagnostic criteria, geographic region, study design, and weight status consistently showed reduced adiponectin levels in PCOS, with no significant subgroup differences. In conclusion, adolescents with PCOS exhibit significantly lower adiponectin levels, consistent with findings in adult populations. These results support an early association between adiponectin dysregulation and PCOS, although further longitudinal studies are needed to clarify clinical utility. Full article
(This article belongs to the Special Issue Molecular Insights in Women’s Health: Advances in Gynecological Disease Mechanisms and Therapeutics)
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14 pages, 286 KB  
Review
Glycomic Insights in Gynecological Disease: From Molecular Mechanisms to Precision Diagnostics and Therapeutics
by Róbert Pásztor and Csaba Váradi
Int. J. Mol. Sci. 2026, 27(3), 1490; https://doi.org/10.3390/ijms27031490 - 3 Feb 2026
Cited by 1 | Viewed by 822
Abstract
Gynecological diseases—encompassing polycystic ovary syndrome, endometriosis, infertility, and malignancies—represent a significant global health burden affecting women’s quality of life, reproductive capacity, and long-term health outcomes. While traditional diagnostics rely on protein-based biomarkers, clinical phenotyping, and imaging, these approaches often lack the sensitivity and [...] Read more.
Gynecological diseases—encompassing polycystic ovary syndrome, endometriosis, infertility, and malignancies—represent a significant global health burden affecting women’s quality of life, reproductive capacity, and long-term health outcomes. While traditional diagnostics rely on protein-based biomarkers, clinical phenotyping, and imaging, these approaches often lack the sensitivity and specificity required for early detection and personalized intervention. Glycomics, the comprehensive study of carbohydrate structures on proteins and lipids, represents an emerging molecular frontier in gynecological disease characterization and therapeutics. This review synthesizes current knowledge regarding glycomic dysregulation across gynecological conditions, elucidates how aberrant glycosylation patterns serve as disease-specific biomarkers, and demonstrates key translational applications, such as glycoform-specific CA-125. By integrating glycomics with complementary omics technologies and artificial intelligence-driven analysis, a transformative diagnostic paradigm is emerging that promises earlier detection, improved risk stratification, and precision-guided therapeutics for women with gynecological disorders. Full article
(This article belongs to the Special Issue Molecular Insights in Women’s Health: Advances in Gynecological Disease Mechanisms and Therapeutics)
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