مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Inflammation and Infertility: Immunopathological Mechanisms, Diagnostic Challenges, and Emerging Therapies
Inflammation and Infertility: Immunopathological Mechanisms, Diagnostic Challenges, and Emerging Therapies
Kasra Taherzadeh,1Saba Safdarpour,2,*
1. Faculty of Modern Sciences, Islamic AzadUniversity of Medical Sciences, Tehran, Iran 2. Faculty of Modern Sciences, Islamic AzadUniversity of Medical Sciences, Tehran, Iran
Introduction: Almost 15 percent of women of reproductive age experience infertility around the world; this percentage is steadily increasing because chronic or dysregulated inflammation in the reproductive system seems to be a major contributing factor. Although physiological response of inflammatory events is normal during some of the processes like ovulation, implantation and tissue remodeling, pathological activation is silent systemic and it can disrupt ovarian functions and endometrial receptivity and embryo development. Examples of such diseases include endometriosis, PCOS, autoimmune disease, and exposure to endocrine-disrupting chemicals, where inflammation has been found to cause reproductive failure. However, the immunopathological basis behind infertility is not fully comprehended. This review is an attempt to clarify the new molecular processes through which inflammation plays a role in inducing infertility, highlighting recent immunopathologic pathways, e.g., activation of inflammasomes, crosstalk between toll-like receptors (TLRs), and the modulation of formation of extracellular vesicles-based immune responses. It also points out the drawbacks of the existing inflammatory indicators in reproductive medicine and considers the new targeted therapies, which hit the imbalances in inflammatory signaling, but not wholesale immunosuppression.
Methods: The PubMed, Scopus, and Embase databases were used to conduct a detailed study of the literature (2005-2025). These were original articles, meta-analyses, and clinical trials, which have been peer-reviewed on inflammatory markers, immigration cell dynamics, and tissue-level alterations in infertile individuals. The most decisive evaluation was provided on in vitro trophoblast and granulosa cells model, reproductive tract biopsies, and animal models (e.g., endometriosis and LPS-induced). The research that focuses on NLRP3 inflammasome signaling, TLR2/4 expression in the endometrial tissue and genes, and exosomal microRNA involvement in the recruitment of immune cells were specifically addressed.
Results: Previously undocumented evidence indicates that ectopic activation of NLRP3 inflammasome multiplexes in the ovary and endometrium could antagonize the folliculogenesis process, damage the quality of oocytes, and prevent the implantation process due to the process of pyroptosis and release of IL-1b. Hyper-activation of TLR4 on granulosa and stromal cells by over-expression activates to hyper-respond to the microbial or damage associated molecular patterns (DAMPs) therefore creating an inflammatory microenvironment that is not supportive of implant. Also, microbiomes of activated macrophages and endometrial cells under stress produce exosomes containing microRNAs (e.g., miR-155, miR21) capable of inhibiting the functions of Tregs and driving Th1 polarization, which compromises maternal immune tolerance. Classical markers tested by a diagnostic, including CRP level or serum cytokines, are not very sensitive when determining localized inflammation, and new markers of inflammation, including EV-derived RNA patterns or inflammasome tissue-specific signatures, would be useful.
Conclusion: The concept of infertility must change so that not only a hormonal or anatomical problem is taken into consideration but also inflammatory-immune disorders. New areas of immunopathology include innate hyperactivation of inflammasomes, hyperresponsiveness of TLRs, and extracellular vesicle-mediated immune tone applied to reduced knowledge on infertility. The future diagnostics and therapies will have to combine these molecular discoveries in order to enable earlier diagnosis and specific immunomodulation. A practical approach to this problem is the creation of specific anti-inflammatory drugs that have fewer systemic inflammatory effects with high reproductive competence like NLRP3 inhibitors or EV based therapies.