ENDOMETRIAL MICROENVIRONMENT DYSFUNCTION: SYSTEMATIC REVIEW ON GENOMIC REPROGRAMMING, IMMUNOLOGY AND IMPACTS ON INFERTILITY
DOI:
https://doi.org/10.56238/levv17n59-024Keywords:
Endometrial Receptivity, Infertility, Epigenetics, EndometriosisAbstract
Objective: The overall objective of this study is to analyze the scientific production on Endometrial Microenvironment Dysfunction (EMD), identifying the molecular, epigenetic, and systemic mechanisms that culminate in female infertility. Methodology: This is a systematic review focused on understanding EMD as a cause of reproductive failure. The research was guided by the question: "What are the pathophysiological bases of endometrial microenvironment dysfunction and its impact on uterine receptivity?". Searches were conducted in scientific databases using combined descriptors: (Endometrial receptivity) AND (Endometriosis) AND (Epigenetics) and (Chronic endometritis) AND (Microbiome) AND (Infertility). 33 high-impact articles were selected for detailed analysis. Results: EMD is characterized by genomic reprogramming (mutations in the ARID1A and KRAS genes) and epigenetic silencing of master genes such as HOXA10. It was identified that obesity (hyperleptinemia) and dysbiosis (CD138+ chronic endometritis) act as insults that alter the implantation window. Pathological angiogenesis via VEGF-A and estrogen-mediated uNK cell cytotoxicity create a hostile environment for the embryo. Conclusion: It is concluded that endometrial dysplasia of the brain (EDB) is a multifactorial condition that requires a transition to precision medicine. Early diagnosis via non-invasive biomarkers (exosomes and miRNAs) and the development of immunomodulatory and non-hormonal therapies are fundamental to restoring fertility and improving the reproductive prognosis of patients.
Downloads
References
BELLVER, J. et al. Endometrial gene expression in the window of implantation is altered in obese women especially in association with polycystic ovary syndrome. Fertility and Sterility, v. 95, n. 7, p. 2335-2341, 2011.
BRICHANT, G. et al. New Therapeutics in Endometriosis: A Review of Hormonal, Non-Hormonal, and Non-Coding RNA Treatments. International Journal of Molecular Sciences, v. 22, n. 19, 10498, 2021.
CAI, X. et al. Phytoestrogens for the Treatment of Endometriosis: Findings and Issues. Pharmaceuticals, v. 14, n. 6, 548, 2021.
CAMBONI, A.; MARBAIX, E. Ectopic Endometrium: The Pathologist’s Perspective. International Journal of Molecular Sciences, v. 22, n. 20, 10974, 2021.
CHEN, L.-H. et al. A Lifelong Impact on Endometriosis: Pathophysiology and Pharmacological Treatment. International Journal of Molecular Sciences, v. 25, n. 4, 2283, 2024.
CLIMA, K. et al. Chronic endometritis — is it time to clarify the diagnostic criteria? Ginekologia Polska, v. 94, n. 2, p. 152–157, 2023.
DON, E. E. et al. Endometrial Angiogenesis of Abnormal Uterine Bleeding and Infertility in Patients with Uterine Fibroids: A Systematic Review. International Journal of Molecular Sciences, v. 24, n. 8, 7011, 2023.
FREGER, S.; LEONARDI, M.; FOSTER, W. G. Exosomes and their cargo are important regulators of cellular function in endometriosis. Reproductive BioMedicine Online, v. 43, n. 3, p. 370-380, 2021.
GHASEMI, F. et al. Dysregulation of microRNAs as Potential Biomarkers for Early Diagnosis of Endometriosis. Biomedicines, v. 10, n. 10, 2558, 2022.
GIUDICE, L. C. et al. Endometriosis in the era of precision medicine and impact on sexual and reproductive health across the lifespan and in diverse populations. FASEB Journal, v. 37, n. 9, e23128, 2023.
GONNELLA, F. et al. The Molecular Link between Obesity and the Endometrial Environment: A Port of Entry for Female Infertility. International Journal of Molecular Sciences, v. 23, n. 10, 5558, 2022.
GUO, C.; ZHANG, C. Role of intestinal microbiota in the pathogenesis of endometriosis: a review. Frontiers in Microbiology, v. 15, 1363455, 2024.
HAMOUDA, R. K. et al. The Comorbidity of Endometriosis and Systemic Lupus Erythematosus: A Systematic Review. Cureus, v. 15, n. 7, e42382, 2023.
KITAYA, K.; YASUO, T. Similarities and Disparities between Endometriosis and Chronic Endometritis: Therapeutic Potential of Novel Antibiotic Treatment Strategy against Ectopic Endometrium. International Journal of Molecular Sciences, v. 24, n. 3, 2059, 2023.
PROVOST, M. P. et al. Pregnancy outcomes decline with increasing body mass index: analysis of 239,127 fresh autologous in vitro fertilization cycles from the 2008–2010 Society for Assisted Reproductive Technology registry. Fertility and Sterility, v. 105, n. 3, p. 663-669, 2016.
RAVEL, J.; MORENO, I.; SIMÓN, C. Bacterial vaginosis and its association with infertility, endometritis, and pelvic inflammatory disease. American Journal of Obstetrics and Gynecology, v. 224, n. 5, p. 487-499, 2021.
VANNUCCINI, S. et al. Hormonal treatments for endometriosis: The endocrine background. Reviews in Endocrine and Metabolic Disorders, v. 23, n. 2, p. 333-355, 2022.
YANG, S. et al. An NK Cell–Estrogen Regulatory Axis in Endometriosis, Related Infertility and Miscarriage. International Journal of Molecular Sciences, v. 25, n. 6, 3362, 2024.
ZERVOU, M. I. et al. Association of endometriosis with Sjögren's syndrome: Genetic insights (Review). International Journal of Molecular Medicine, v. 53, n. 20, 2024.
