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Cite as: Archiv EuroMedica. 2026. 16; 4. DOI 10.35630/2026/16/Iss.4.18

Received 22 June 2026;
Accepted 7 August 2026;
Published 11 August 2026

CHRONIC TONSILLITIS AS A POTENTIAL SOURCE OF PROSTATIC INFLAMMATION AND MALE REPRODUCTIVE DYSFUNCTION: AN INTEGRATIVE PATHOPHYSIOLOGICAL HYPOTHESIS

Viktor Paramonov¹ , Lev Vysotskiy¹ ,
Egor Paramonov¹ , Pavel Shchennikov¹ ,
Georgiy Potemkin¹ , Aleksey Dugin¹ ,
Andrey Tantsyrev¹ , Artem Albutov¹ , Alexander Derevyanov¹ ,
Yuriy Emelyanov¹

¹ JSC Doctor Paramonov Clinic, Saratov, Russia

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  klinika@dr-paramonov.ru

ABSTRACT

Background

Chronic tonsillitis is associated with persistent microbial and immunoinflammatory stimulation and may be linked to systemic inflammatory activity. Its possible role in prostatic inflammation and male reproductive dysfunction remains insufficiently studied.

Aim

To formulate and pathophysiologically substantiate a hypothesis on the possible association between chronic tonsillitis, prostatic inflammation and male reproductive dysfunction.

Materials and Methods

A narrative conceptual review was conducted using publications identified in PubMed/MEDLINE, Scopus, Web of Science and Google Scholar up to March 31, 2026. The analysis included 89 sources published between 1993 and 2026.

Results

No direct clinical studies were identified that simultaneously evaluated chronic tonsillitis, prostatic inflammation and male reproductive function. The proposed model includes two possible pathways: a direct systemic effect of chronic tonsillar inflammation on the testis and spermatozoa and an indirect effect mediated by chronic prostatic inflammation. Individual components of the model are supported by data on systemic inflammation, oxidative stress, blood testis barrier disruption, altered spermatogenesis, immune dysregulation and chronic prostatic inflammation. The most hypothetical components remain tonsillar prostatic microbial translocation, migration of activated tonsillar lymphocytes, tonsillogenic induction of antisperm antibodies and specific epigenetic changes.

Conclusions

Chronic tonsillitis cannot be regarded as a proven cause of prostatic inflammation or male reproductive dysfunction. The presented model is a testable pathophysiological hypothesis and requires direct prospective clinical and experimental studies.

Keywords: chronic tonsillitis, chronic prostatitis, male reproductive dysfunction, systemic inflammation, oxidative stress, blood testis barrier, microbial translocation.

INTRODUCTION

Chronic tonsillitis is a persistent inflammatory disease of the palatine tonsils, in which long-term bacterial colonization of tonsillar crypts and biofilm formation may support local immune activation [1,11,17]. In addition to local inflammatory changes, chronic tonsillar disease may be associated with systemic inflammatory activity, and reductions in selected inflammatory markers have been reported after tonsillectomy or adenotonsillectomy [18,27,28].

The concept of chronically inflamed tonsils as a potential source of injury to distant organs is based on the theory of tonsillar focal infection and tonsil-induced immunoinflammatory disorders [2,14,15]. Similar mechanisms have been proposed in the pathogenesis of IgA nephropathy, psoriasis, rheumatoid arthritis, and other diseases [2,14,15]. However, the prostate gland and the male reproductive system remain insufficiently investigated as potential target organs of chronic tonsillar inflammation.

Chronic prostatitis and chronic pelvic pain syndrome are characterized by a complex and heterogeneous pathogenesis [3,51]. Infectious, immune, autoimmune, and neuroinflammatory mechanisms all contribute to the development of these conditions [3,4,51,52]. The persistence of clinical manifestations despite the absence of an infectious agent detectable by standard diagnostic methods in a proportion of patients supports the hypothesis that systemic inflammatory signals originating from distant chronic inflammatory foci may play a role. However, in the case of chronic tonsillitis, this potential association remains theoretical and has not yet been demonstrated.

The male reproductive system is highly susceptible to systemic inflammation and oxidative stress [12,29,30]. Male reproductive dysfunction may result both from the direct systemic effects of inflammation on the testes and spermatozoa [12,33–36] and from indirect mechanisms mediated by prostatic inflammation, alterations in the composition of seminal plasma, and changes in the local immune microenvironment [29,30,52]. However, direct clinical evidence demonstrating a causal relationship between chronic tonsillitis and these abnormalities is currently lacking.

Relevance

The rationale for the present study stems from the fact that, despite accumulating evidence of the systemic effects of chronic tonsillitis [18,27,28] and the established role of inflammation in the pathogenesis of prostatic and male reproductive disorders [1,2,29,30,51,52], the potential relationship between chronic tonsillitis, prostatic inflammation, and male reproductive dysfunction has not yet been comprehensively evaluated from a pathophysiological perspective.

Novelty

The novelty of this study lies in the development of an integrative pathophysiological hypothesis linking chronic tonsillitis, prostatic inflammation, and male reproductive dysfunction. The proposed model incorporates both a direct systemic effect of chronic tonsillar inflammation on the male reproductive system and a potential indirect effect mediated through prostatic inflammation. Rather than asserting a proven causal relationship, the model provides a testable conceptual framework for future experimental and clinical investigations.

AIM

To formulate and provide a pathophysiological rationale for the hypothesis of a possible association between chronic tonsillitis, prostatic inflammation, and male reproductive dysfunction.

Research Objectives

1. To characterize chronic tonsillitis as a potential source of systemic inflammatory burden.
2. To analyze the potential association between chronic tonsillitis and prostatic inflammation.
3. To evaluate the potential mechanisms by which systemic and prostatic inflammation may contribute to male reproductive dysfunction.
4. To integrate the available evidence into a pathophysiological model and identify the limitations of this model.

MATERIALS AND METHODS

This study was conducted as a narrative conceptual review. The objective of the review was to formulate and provide a pathophysiological rationale for the hypothesis of a possible association between chronic tonsillitis, prostatic inflammation, and male reproductive dysfunction.

A literature search was performed in PubMed/MEDLINE, Scopus, and Web of Science without restriction on the starting date through March 31, 2026. Google Scholar was additionally used to identify relevant publications and to screen the reference lists of included studies. The included literature was published between 1993 and 2026.

The main search terms included chronic tonsillitis, tonsillar focal infection, tonsillar microbiota, tonsillar biofilm, systemic inflammation, oxidative stress, microbial translocation, bacteremia, endotoxemia, chronic prostatitis, chronic pelvic pain syndrome, prostatic inflammation, male infertility, semen quality, blood–testis barrier, Sertoli cells, Leydig cells, steroidogenesis, spermatogenesis, molecular mimicry, antisperm antibodies, and seminal microbiome. Search terms were combined using the Boolean operators AND and OR according to the specific component of the proposed hypothesis being investigated.

The review included original clinical and experimental studies, systematic reviews, meta-analyses, narrative reviews, and selected foundational publications that provided evidence relevant to one or more components of the proposed hypothesis, including chronic tonsillitis, systemic inflammation, microbial translocation, chronic prostatic inflammation, male reproductive dysfunction, the blood–testis barrier, steroidogenesis, spermatogenesis, semen parameters, and autoimmune mechanisms. Studies involving humans, animal models, and cell culture models were considered. The inclusion of experimental studies was justified by the limited availability of direct clinical evidence addressing the proposed association.

Duplicate records, publications not aligned with the objective of the review, and studies lacking data on the inflammatory, immunological, microbial, oxidative, neuroendocrine, or reproductive mechanisms under consideration were excluded. After removal of duplicate and irrelevant records, a total of 89 publications were included in the final analysis.

Data were synthesized using a thematic approach. The evidence was conceptually classified into three levels: (1) evidence directly related to chronic tonsillitis; (2) evidence describing corresponding mechanisms involved in prostatic inflammation or male reproductive dysfunction; and (3) hypothetical links derived through pathophysiological extrapolation.

In the final stage, the available evidence was integrated into a pathophysiological model comprising two potential pathways: (1) a direct systemic effect of chronic tonsillar inflammation on male reproductive function and (2) an indirect effect mediated through prostatic inflammation.

A formal assessment of the risk of bias and a standardized quality appraisal of the included publications were not performed. Likewise, no statistical pooling of results or meta-analysis was conducted because this study was designed as a narrative conceptual review integrating methodologically heterogeneous clinical, experimental, and review studies.

RESULTS

A total of 89 unique publications published between 1993 and 2026 were included in the final analysis. The reviewed literature comprised clinical and epidemiological studies, experimental studies using animal and cell culture models, systematic and narrative reviews, meta-analyses, and selected foundational investigations. No clinical studies were identified that specifically evaluated the association between chronic tonsillitis, prostatic inflammation, and male reproductive dysfunction simultaneously. Therefore, the findings were synthesized according to the individual pathophysiological mechanisms underlying the proposed association.

Chronic Tonsillitis as a Source of Persistent Microbial and Immunoinflammatory Stimulation

Studies of tonsillar tissue have shown that, in chronic and recurrent inflammation, the crypts of the palatine tonsils harbor polymicrobial communities and bacterial biofilms. These biofilms contain Fusobacterium nucleatum, Streptococcus spp., Prevotella spp., Porphyromonas spp., and other microorganisms capable of sustaining prolonged activation of both the innate and adaptive immune systems [4,11,37].

Functional alterations of T lymphocytes and impaired local immune regulation have been described in chronically inflamed tonsillar tissue [17,54]. In several diseases, chronically inflamed tonsils are regarded as a potential source of systemic autoimmune or inflammatory responses, accompanied by immune cell activation and pathological processes affecting distant organs [3,14,15].

Indirect evidence of the systemic effects of chronic tonsillar inflammation includes alterations in the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR), as well as reductions in selected inflammatory markers following tonsillectomy or adenotonsillectomy [18,27,28]. In one study, the neutrophil-to-lymphocyte ratio decreased significantly after tonsillectomy (p = 0.045), and postoperative values did not differ significantly from those of the control group (p = 0.584) [27]. In a meta-analysis, adenotonsillectomy was associated with a reduction in C-reactive protein levels, with a standardized mean difference of −0.946 (95% CI, −1.578 to −0.314) [28]. These findings support the presence of a systemic inflammatory burden associated with chronic tonsillar inflammation but do not demonstrate a direct effect on the prostate gland or the male reproductive system.

Potential Dissemination of Microorganisms and Bacterial Components

The available literature supports the biological plausibility of hematogenous and lymphatic dissemination of microorganisms from oropharyngeal infectious foci [5,6]. For Streptococcus pyogenes, experimental studies have demonstrated extracellular dissemination through lymphatic vessels and lymph nodes, followed by entry into the systemic circulation [6]. In chronic inflammatory diseases of the oral cavity, translocation of bacterial components into the bloodstream, including lipopolysaccharide (LPS), has also been described [7,8].

However, no direct evidence was identified demonstrating the translocation of bacteria from the tonsillar crypts to the prostate gland or seminal fluid. Therefore, tonsil-to-prostate microbial translocation remains a hypothetical component of the proposed pathophysiological model.

Immunoinflammatory Mechanisms of Chronic Prostatic Inflammation

Studies of chronic prostatitis and chronic pelvic pain syndrome have consistently demonstrated evidence of cytokine activation, immune dysregulation, and autoimmune responses [1,2,51,52]. A meta-analysis including 34 studies reported increased levels of TNF-α, IL-1β, IL-6, and IL-8 in the majority of biological samples obtained from patients with chronic prostatitis/chronic pelvic pain syndrome, as well as in experimental models [51].

In experimental autoimmune prostatitis, IL-6 was shown to impair the function of regulatory T cells and exacerbate the Th17/Treg imbalance [1]. In patients with chronic prostatitis/chronic pelvic pain syndrome, Th1- and Th17-mediated immune responses directed against prostatic and seminal antigens have also been identified [52].

Activation of NF-κB and STAT3 signaling pathways, involvement of TLR4-mediated signaling, reactive oxygen species (ROS)-dependent alterations, and the establishment of self-sustaining inflammatory cascades have been described in prostatic tissue and experimental models [22,23,25]. These findings support the existence of persistent inflammatory mechanisms underlying chronic prostatic inflammation but do not indicate that the initiating inflammatory signals originate from chronic tonsillar disease.

Thus, prostatic inflammation may persist even in the absence of an infectious agent detectable by standard diagnostic methods. This provides a pathophysiological basis for the hypothesis that systemic inflammatory signals originating from a distant chronic inflammatory focus may amplify or sustain local inflammation within the prostate gland.

Bacterial DNA and the Prostatic Microbiota

In a study of prostate tissue, bacterial DNA sequences were detected in 79 of 170 patients with chronic prostatitis (46.4%) and in 21 of 107 patients with prostate cancer (19.6%) (p < 0.0001) [21]. These findings demonstrate the presence of bacterial genetic material in prostatic tissue in a substantial proportion of patients with chronic inflammation.

However, the detection of bacterial DNA does not establish the presence of viable microorganisms, active infection, or a tonsillar origin of the detected bacteria. Therefore, these findings should be regarded only as indirect evidence supporting a possible contribution of microbial factors to prostatic inflammation.

Association between Chronic Prostatic Inflammation and Male Reproductive Function

In patients with chronic prostatitis/chronic pelvic pain syndrome, autoreactive Th1- and Th17-mediated immune responses directed against prostatic and seminal antigens have been associated with impaired semen quality [52]. Prostatic inflammation may adversely affect male reproductive function through multiple mechanisms, including alterations in the composition of seminal plasma, increased local oxidative stress, cytokine- and immune cell-mediated damage to spermatozoa, and impaired secretory function of the prostate gland [29,30,36,52].

Studies of the seminal microbiome and genital tract infections have also shown that the presence of pathogenic microorganisms and chronic infectious burden may be associated with alterations in sperm concentration, motility, and other semen parameters [41,82,85]. However, these findings do not establish a specific role for chronic tonsillitis.

The key studies forming the evidence base for the proposed pathophysiological model are summarized in Table 1.

The available evidence supports the individual components of chronic tonsillar, prostatic, and reproductive inflammation. However, no studies have directly evaluated the entire proposed sequence linking chronic tonsillitis to prostatic inflammation and, subsequently, to male reproductive dysfunction.

Systemic Inflammation, Oxidative Stress, and Sperm Damage

Oxidative stress is one of the best-established mechanisms underlying male infertility [12,13,16,29,30]. Excessive production of reactive oxygen species (ROS) can damage sperm membrane lipids, proteins, and DNA, impair the acrosome reaction, and reduce the functional competence of spermatozoa [12,13,16]. The high susceptibility of spermatozoa to oxidative injury is largely attributable to their high content of polyunsaturated fatty acids and their limited intracellular antioxidant defenses [12,13,16].

Chronic inflammation and infectious processes can exacerbate oxidative stress and the associated damage to male germ cells [29,30,36]. However, no studies were identified demonstrating increased oxidative sperm damage specifically in men with chronic tonsillitis. Therefore, the proposed sequence linking chronic tonsillar inflammation to systemic oxidative stress and subsequent sperm damage is biologically plausible but is currently supported only by indirect evidence.

Disruption of the Blood–Testis Barrier and Testicular Cell Function

Experimental studies have demonstrated that IL-6 can impair the integrity of the blood–testis barrier and alter the localization of tight junction proteins in Sertoli cells [33,34]. In a model of autoimmune orchitis, IL-6 exposure was associated with seminiferous tubule damage and increased permeability of the blood–testis barrier [34].

TNF-α and bacterial lipopolysaccharide (LPS) have also been shown to exert damaging effects on the testis and epididymis [35,36]. In an experimental model, LPS-induced inflammation disrupted spermatogenesis, steroidogenesis, and blood–testis barrier permeability, whereas the absence of TNF-α or its pharmacological inhibition reduced the severity of these alterations [35].

These findings demonstrate that inflammatory mediators and bacterial components can damage testicular structures in experimental models. However, it remains unclear whether such mediators and components reach concentrations during chronic tonsillitis that are sufficient to disrupt the blood–testis barrier or impair testicular cell function.

Endocrine Mechanisms

Clinical and experimental studies have demonstrated that endotoxin-induced inflammation may reduce testosterone production [86]. In healthy men, administration of low-dose endotoxin was associated with an inflammatory response and subsequent decline in testosterone levels without corresponding changes in luteinizing hormone or follicle-stimulating hormone concentrations, suggesting a potential direct inhibitory effect on Leydig cell function [86].

Proinflammatory cytokines may also disrupt the regulation of the hypothalamic–pituitary–gonadal axis and testicular steroidogenesis [86–88]. However, no direct evidence of altered reproductive hormone profiles in men with chronic tonsillitis was identified in the reviewed literature. Therefore, the endocrine pathway represents a plausible but currently unproven component of the proposed hypothesis.

Autoimmune Mechanisms and Antisperm Antibodies

Disruption of the blood–testis barrier may lead to the exposure of germ cell antigens and the development of autoimmune responses [31,32]. Antisperm antibodies can bind to surface antigens of spermatozoa and impair their motility, including through mechanisms involving sperm agglutination and immobilization [39,40].

The literature describes cross-reactivity between carbohydrate antigenic determinants of spermatozoa, somatic cells, and infectious agents [39]. Streptococcal infections may also be associated with autoimmune reactions mediated by molecular mimicry mechanisms [76]. However, specific cross-reactivity between antigens of tonsillar microorganisms and antigens of spermatozoa or testicular tissues has not been directly investigated.

Thus, tonsil-derived induction of antisperm antibodies remains a hypothetical mechanism. Available evidence supports the possibility of autoimmune responses following disruption of the immunological isolation of the testis and demonstrates the presence of shared antigenic determinants between spermatozoa and infectious agents; however, it does not prove that chronic tonsillitis leads to the formation of antisperm antibodies [31,32,39].

Epigenetic Alterations

Epigenetic mechanisms play an important role in the regulation of spermatogenesis and male reproductive function [63–66]. Oxidative stress may also contribute to epigenetic alterations affecting sperm function [67].

In chronic prostatitis/chronic pelvic pain syndrome, epigenetic changes have been described in immunoregulatory loci, including IL10, FOXP3, CD274, and TNF [55], as well as hypermethylation of promoter regions of ESR1 and ESR2 in somatic cells of ejaculate [56].

No data were identified regarding specific epigenetic alterations in spermatozoa, testicular cells, or immune cells in men with chronic tonsillitis. Therefore, the epigenetic component should be regarded only as an additional hypothetical mechanism rather than an established consequence of chronic tonsillar inflammation.

Evidence from Tonsillectomy Studies

Following tonsillectomy and adenotonsillectomy, reductions in systemic inflammatory markers have been reported in several studies. In patients with chronic tonsillitis, the neutrophil-to-lymphocyte ratio decreased significantly after tonsillectomy (p = 0.045) [27]. Another study demonstrated reductions in both neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios after adenotonsillectomy [18]. A meta-analysis showed that adenotonsillectomy in children with obstructive sleep apnea was associated with decreased C-reactive protein levels [28]. However, these studies differed in terms of surgical indications and patient characteristics.

In a large national cohort study including 179,875 patients who underwent tonsillectomy, the standardized incidence ratio for autoimmune diseases was 1.34 (95% CI, 1.30–1.37) [68]. In another population-based cohort study, surgical removal of lymphoid tissue of the Waldeyer ring was associated with an increased risk of Sjögren syndrome (HR 1.52; 95% CI, 1.23–1.87). Among individuals who underwent surgery before the age of 18 years, the hazard ratio was 2.27 [69].

These findings do not support considering tonsillectomy as a therapeutic strategy for correcting prostatic inflammation or male reproductive dysfunction in the absence of dedicated clinical studies. They demonstrate reductions in selected inflammatory markers after surgery but also highlight the complexity and potential ambiguity of its long-term immunological consequences.

Integrative Pathophysiological Model

Synthesis of the available evidence allowed the identification of two major pathways through which chronic tonsillitis may potentially influence male reproductive function.

The first pathway involves a direct systemic effect of the chronic tonsillar inflammatory focus. Persistent polymicrobial communities and biofilms within tonsillar crypts may sustain local microbial and immune stimulation [4,11,17,37]. The reduction of selected inflammatory markers following tonsillectomy indirectly suggests a possible systemic component of this inflammatory process [18,27,28]. Potential consequences of such systemic inflammatory burden may include oxidative damage to spermatozoa, disruption of the blood–testis barrier, alterations in Sertoli and Leydig cell function, impaired steroidogenesis and spermatogenesis, as well as autoimmune responses resulting from disruption of the immunological isolation of the testis [12,13,16,29,30,31,32,33–36,39,40,86–88].

The second pathway involves an intermediate role of the prostate gland. The potential contribution of oral inflammatory foci to prostatic inflammation is indirectly supported by studies of periodontitis and by the detection of bacterial DNA in prostate tissue [9,10,19,21]. Systemic inflammatory signals may amplify or sustain prostatic inflammatory and immune pathways [1,22,23,25,51]. Chronic prostatic inflammation, in turn, may be associated with autoreactive Th1- and Th17-mediated responses against prostatic and seminal antigens, as well as impaired semen quality [52].

The most strongly supported components of the proposed model include the presence of polymicrobial communities and immune alterations in tonsillar tissue [4,11,17,37], reductions in selected inflammatory markers following tonsillectomy [18,27,28], the role of inflammatory mediators and signaling pathways in prostatic and testicular inflammation [1,22,23,25,33–36,51], the detrimental effects of oxidative stress on spermatozoa [12,13,16,29,30], and the association between chronic prostatitis/chronic pelvic pain syndrome and impaired semen quality [52].

The most hypothetical components remain direct tonsil-to-prostate microbial translocation, migration of activated tonsillar lymphocytes to the prostate gland, tonsil-derived induction of antisperm antibodies, and specific epigenetic alterations affecting the reproductive system.

The key pathophysiological components of the proposed model are presented in Table 2, while the levels of supporting evidence are summarized in Table 3. The present analysis indicates that the model is based on established individual pathophysiological mechanisms and indirect evidence; however, the overall association between chronic tonsillitis, prostatic inflammation, and male reproductive dysfunction remains hypothetical and requires direct experimental and clinical validation.

DISCUSSION

This narrative conceptual review integrates evidence on chronic tonsillitis, prostatic inflammation, and male reproductive dysfunction into a pathophysiological model. The analysis does not establish a direct causal relationship between these conditions but demonstrates the biological plausibility of such an association based on the individual mechanisms discussed in the preceding sections.

A key feature of the proposed model is the distinction between two potential pathways through which chronic tonsillitis may influence male reproductive function. The first pathway involves a direct systemic effect of inflammatory, bacterial, and oxidative factors on the testes and spermatozoa [12,33–36]. The second pathway involves an indirect role of the prostate gland, in which systemic inflammatory signals or potential microbial translocation may contribute to the persistence of chronic inflammation and affect semen quality [21,51,52].

Within the direct pathway, the role of systemic inflammation and oxidative stress is the most strongly supported component. These mechanisms have been extensively investigated in inflammatory diseases, urogenital infections, and other conditions associated with male infertility [12,29,30,36]. However, direct evidence demonstrating comparable sperm damage specifically in the context of chronic tonsillitis is currently lacking.

A potentially important component of the proposed model is disruption of the blood–testis barrier. Experimental data indicate that IL-6, TNF-α, and lipopolysaccharide can increase the permeability of this barrier and impair the microenvironment required for normal spermatogenesis [33–35]. Such disruption may also promote the exposure of germ cell antigens to the immune system, thereby creating conditions conducive to autoimmune responses and the formation of antisperm antibodies [31,32,39].

The endocrine component of the proposed model is also biologically plausible. Endotoxin-induced inflammation and proinflammatory cytokines may impair testosterone production, Leydig cell function, and regulation of the hypothalamic–pituitary–gonadal axis [86–88]. However, studies simultaneously assessing reproductive hormone profiles and spermatogenic parameters in men with chronic tonsillitis are currently lacking. Therefore, the endocrine pathway remains an extrapolation of findings obtained in other inflammatory conditions.

The indirect pathway involving the prostate gland has independent pathophysiological relevance. Chronic prostatitis and chronic pelvic pain syndrome are characterized by cytokine activation, immune dysregulation, and self-sustaining inflammatory cascades [1,2,51,52]. These processes may persist even in the absence of detectable bacterial infection. Therefore, systemic inflammatory signals originating from a distant chronic inflammatory focus could theoretically amplify pre-existing prostatic inflammation or lower the threshold for its transition to a chronic state.

The association between chronic prostatic inflammation and impaired semen quality is of particular importance for the proposed model. In patients with chronic prostatitis/chronic pelvic pain syndrome, autoreactive Th1- and Th17-mediated responses against prostatic and seminal antigens have been associated with reduced semen quality [52]. Therefore, the prostate gland may represent a potential intermediate link between systemic inflammatory exposure and impaired male reproductive function.

The hypothesis of microbial translocation requires cautious interpretation. The possibility of hematogenous and lymphatic dissemination of microorganisms from oropharyngeal foci has been demonstrated [5,6], and bacterial DNA has been detected in prostate tissue in a proportion of patients with chronic prostatitis [21]. However, direct evidence of microbial translocation from tonsillar crypts to prostatic tissue or seminal fluid is currently lacking. Therefore, tonsil-to-prostate microbial translocation remains a hypothetical mechanism and requires molecular confirmation through identification of identical microbial strains.

The autoimmune component of the proposed model also remains largely hypothetical. Streptococcal infections may trigger autoimmune responses through molecular mimicry mechanisms [76], chronically inflamed tonsils are considered a potential source of systemic immune activation in certain diseases [3,14,15], and cross-reactivity has been described between some bacterial and sperm-associated carbohydrate epitopes [39]. However, specific cross-reactivity between antigens of tonsillar microorganisms and components of the male reproductive system has not been directly investigated.

Epigenetic mechanisms may contribute to the long-term persistence of inflammatory or reproductive phenotypes. In chronic prostatitis/chronic pelvic pain syndrome, epigenetic alterations in immunoregulatory loci and estrogen receptor genes have been described in somatic cells of ejaculate [55,56]. Alterations in epigenetic regulation have also been reported in male infertility, while oxidative stress is considered a potential contributor to epigenetic dysregulation in spermatozoa [63–67]. However, evidence of specific epigenetic effects induced by chronic tonsillitis is currently lacking. Therefore, this component should be regarded as a potential area for future research rather than an established mechanism.

Validation of the proposed model requires a series of well-designed clinical and experimental studies. At the initial stage, men with chronic tonsillitis should be compared with control groups regarding semen parameters, sperm DNA fragmentation, antisperm antibodies, oxidative stress markers, reproductive hormone profiles, and systemic cytokine patterns. Chronic prostatitis or chronic pelvic pain syndrome should be evaluated separately as a potential intermediate factor.

Further studies should include assessment of changes in these parameters following treatment of chronic tonsillitis, parallel sequencing of the microbiota of tonsillar crypts, prostatic secretions, and seminal fluid, as well as investigation of cross-reactivity between tonsillar bacterial antigens and sperm antigens.

Thus, the proposed model demonstrates internal pathophysiological coherence and integrates several established mechanisms of systemic, prostatic, and reproductive inflammation. However, a causal relationship has not yet been demonstrated. Chronic tonsillitis should not be considered an established cause of male reproductive dysfunction but rather a potential source of systemic inflammatory burden, the clinical significance of which requires dedicated investigation.

Practical Implications

The practical significance of the proposed model lies in the development of new directions for clinical assessment and scientific investigation rather than in modifying current therapeutic approaches. In men with chronic tonsillitis accompanied by reproductive dysfunction or chronic pelvic pain, evaluation of systemic inflammatory markers, prostate status, and semen parameters may be considered as part of standard diagnostic assessment. However, the available evidence does not support recommending tonsillectomy or other treatments for chronic tonsillitis as a primary strategy for correcting prostatic inflammation or male reproductive dysfunction. Clinical decisions should remain based on established indications, while the proposed model may serve as a framework for patient selection and outcome assessment in future prospective studies.

Limitations

This study has several limitations.

First, the review was conducted as a narrative conceptual analysis. A formal assessment of the risk of bias and a standardized quality appraisal of the included studies were not performed, limiting the ability to quantitatively compare findings and determine the overall strength of the available evidence.

Second, the reviewed literature lacked direct clinical studies simultaneously evaluating chronic tonsillitis, prostatic inflammation, and male reproductive function. A substantial proportion of the proposed model is based on the integration of evidence obtained separately from studies of chronic tonsillitis, chronic prostatitis, systemic inflammation, experimental orchitis, periodontitis, and male infertility.

Third, part of the available evidence has been derived from animal models and cell culture studies. The concentrations of cytokines, lipopolysaccharide, and other inflammatory mediators used in these experimental systems may not correspond to the levels present in chronic tonsillitis in humans. Therefore, translation of these findings into clinical settings requires cautious interpretation.

Fourth, the detection of bacterial DNA in prostate tissue or prostatic secretions does not demonstrate the presence of viable microorganisms, active infection, or their origin from a tonsillar focus [9,21]. The reviewed studies did not include molecular comparison of microorganisms from tonsillar crypts and the prostate at the level of identical microbial strains.

Fifth, autoimmune and epigenetic mechanisms have not been directly investigated in the context of chronic tonsillitis. There are no data demonstrating specific cross-reactivity between tonsillar bacterial antigens and sperm or testicular tissue antigens, nor are there established epigenetic signatures characteristic of men with chronic tonsillitis.

Sixth, the included studies were heterogeneous in terms of study design, populations, diagnostic criteria, and methods used to assess inflammation, microbiota, and semen parameters. This heterogeneity limits direct comparison of findings and precludes justified statistical pooling of the available data.

Seventh, the influence of potential confounding factors cannot be excluded, including age, obesity, smoking, varicocele, metabolic disorders, urogenital infections, medication use, and other chronic inflammatory conditions.

Therefore, the proposed pathophysiological model should be regarded as a testable hypothesis rather than an established causal relationship.

CONCLUSIONS

1. Chronic tonsillitis may be considered a potential source of persistent microbial and immunoinflammatory stimulation, which may be associated with systemic inflammatory activity and the release of bacterial components into the bloodstream.
2. Prostatic inflammation may theoretically be sustained by systemic inflammatory signals originating from a distant chronic inflammatory focus through cytokine activation, immune dysregulation, and self-perpetuating inflammatory cascades. Direct tonsil-to-prostate microbial translocation, however, has not been demonstrated.
3. The potential influence of chronic tonsillitis on male reproductive function may be mediated directly through systemic inflammation, oxidative stress, disruption of the blood–testis barrier, impairment of Sertoli and Leydig cell function, altered steroidogenesis and spermatogenesis, and indirectly through chronic prostatic inflammation.
4. The proposed pathophysiological model should be regarded as a testable hypothesis rather than an established causal relationship. Validation of this model requires prospective studies with simultaneous assessment of chronic tonsillitis, prostate status, semen parameters, reproductive hormone profiles, systemic inflammation and oxidative stress markers, as well as molecular comparison of the microbiota of tonsillar crypts, prostatic secretions, and seminal fluid.

DISCLOSURE

Author Contributions

Conceptualization: Viktor Paramonov, Lev Vysotskiy. Methodology: Viktor Paramonov, Lev Vysotskiy, Egor Paramonov. Writing – original draft: Viktor Paramonov, Artem Albutov. Writing - review and editing: Viktor Paramonov, Artem Albutov. Visualization: Egor Paramonov, Pavel Shchennikov. Supervision: Alexander Derevyanov, Egor Paramonov, Yuriy Emelyanov. Literature search and selection: all authors.

Final approval of the manuscript: all authors.

Funding

No external funding was received for this manuscript.

Conflicts of Interest

The authors declare no conflict of interest.

Ethical approval

Not applicable.

Data availability

Not applicable.

Use of Artificial Intelligence

AI was used only as an auxiliary tool to support the literature search and language editing. All references, scientific interpretations, conclusions, and the final version of the manuscript were independently checked and approved by the authors. The authors accept full responsibility for the scientific content and final wording of the manuscript.

REFERENCES

1. Jensen A, Fagö-Olsen H, Sørensen CH, Kilian M. Molecular mapping to species level of the tonsillar crypt microbiota associated with health and recurrent tonsillitis. PLoS One. 2013;8(2):e56418. https://doi.org/10.1371/journal.pone.0056418
2. Liu X, Bian X, Han S, et al. IL-6 exacerbates experimental autoimmune prostatitis by disrupting STAT5a-mediated Treg cell function and Th17/Treg balance. Mediators Inflamm. 2026;2026(1):e2600849. https://doi.org/10.1155/mi/2600849
3. Li Z, Yan R, Lao Y, et al. Immune cells in chronic prostatitis/chronic pelvic pain syndrome: from pathological mechanisms to therapeutic opportunities. Cell Signal. 2026;145:112623. https://doi.org/10.1016/j.cellsig.2026.112623
4. Tang Z, Wu J, Dong M, Li C, Wang R. Deciphering the underlying mechanisms linking psoriasis and IgA nephropathy. J Immunol Res. 2026;2026(1):e1862174. https://doi.org/10.1155/jimr/1862174
5. Gendron R, Grenier D, Maheu-Robert L. The oral cavity as a reservoir of bacterial pathogens for focal infections. Microbes Infect. 2000;2(8):897-906. https://doi.org/10.1016/S1286-4579(00)00391-9
6. Siggins MK, Lynskey NN, Lamb LE, et al. Extracellular bacterial lymphatic metastasis drives Streptococcus pyogenes systemic infection. Nat Commun. 2020;11(1):4697. https://doi.org/10.1038/s41467-020-18454-0
7. Liljestrand JM, Paju S, Buhlin K, et al. Lipopolysaccharide, a possible molecular mediator between periodontitis and coronary artery disease. J Clin Periodontol. 2017;44(8):784-792. https://doi.org/10.1111/jcpe.12751
8. Pussinen PJ, Kopra E, Pietiäinen M, et al. Periodontitis and cardiometabolic disorders: the role of lipopolysaccharide and endotoxemia. Periodontol 2000. 2022;89(1):19-40. https://doi.org/10.1111/prd.12433
9. Estemalik J, Demko C, Bissada NF, et al. Simultaneous detection of oral pathogens in subgingival plaque and prostatic fluid of men with periodontal and prostatic diseases. J Periodontol. 2017;88(9):823-829. https://doi.org/10.1902/jop.2017.160477
10. Peinado BRR, Nazário RMF, Frazão DR, et al. Is there any association between periodontitis and prostatic alterations? A systematic review. Prostate. 2025;85(15):1369-1385. https://doi.org/10.1002/pros.70029
11. Diaz RR, Picciafuoco S, Paraje MG, et al. Relevance of biofilms in pediatric tonsillar disease. Eur J Clin Microbiol Infect Dis. 2011;30(12):1503-1509. https://doi.org/10.1007/s10096-011-1249-3
12. Barati E, Nikzad H, Karimian M. Oxidative stress and male infertility: current knowledge of pathophysiology and role of antioxidant therapy in disease management. Cell Mol Life Sci. 2020;77(1):93-113. https://doi.org/10.1007/s00018-019-03253-8
13. Zhou Y, Zhang H, Yan H, et al. Deciphering the role of oxidative stress in male infertility: insights from reactive oxygen species to antioxidant therapeutics. Front Biosci Landmark Ed. 2025;30(4):27046. https://doi.org/10.31083/FBL27046
14. Ikeda T, Takeuchi H, Takahashi K, et al. Tonsillectomy improved therapeutic response in anti-SRP myopathy with chronic tonsillitis. Front Immunol. 2020;11:595480. https://doi.org/10.3389/fimmu.2020.595480
15. Li J, Li S, Jin J, et al. The aberrant tonsillar microbiota modulates autoimmune responses in rheumatoid arthritis. JCI Insight. 2024;9(18):e175916. https://doi.org/10.1172/jci.insight.175916
16. Raj CJ, Aishwarya CVS, Mounika KVSSN, et al. Deciphering the nexus between oxidative stress and spermatogenesis: a compendious overview. Adv Exp Med Biol. 2022;1391:1-16. https://doi.org/10.1007/978-3-031-12966-7_1
17. Geißler K, Markwart R, Requardt RP, et al. Functional characterization of T-cells from palatine tonsils in patients with chronic tonsillitis. PLoS One. 2017;12(9):e0183214. https://doi.org/10.1371/journal.pone.0183214
18. Kim JM, Choi JS. The analysis of neutrophil to lymphocyte ratio, lymphocyte to monocyte ratio, and platelet to lymphocyte ratio in patients with adenoidectomy and tonsillectomy. J Clin Med. 2024;13(18):5457. https://doi.org/10.3390/jcm13185457
19. Fu E, Cheng CM, Chung CH, et al. Association of chronic periodontitis with prostatic hyperplasia and prostatitis: a population-based cohort study in Taiwan. J Periodontol. 2021;92(1):72-86. https://doi.org/10.1002/JPER.19-0706
20. Okada K, Takezawa K, Tsujimura G, et al. Localization and potential role of prostate microbiota. Front Cell Infect Microbiol. 2022;12:1048319. https://doi.org/10.3389/fcimb.2022.1048319
21. Krieger JN, Riley DE, Vesella RL, et al. Bacterial DNA sequences in prostate tissue from patients with prostate cancer and chronic prostatitis. J Urol. 2000;164(4):1221-1228. https://doi.org/10.1016/S0022-5347(05)67145-5
22. Zhang F, Zhang A, Meng T, et al. Epithelial redox stress programs macrophage immunometabolism through a ZNF24-MIF-NF-κB pathway in chronic nonbacterial prostatitis. Redox Biol. 2026;90:104042. https://doi.org/10.1016/j.redox.2026.104042
23. Wu W, Meng T, Wang Y, Chen J, Liang C. Prdx5 regulates macrophage polarization by modulating the TLR4/NF-κB pathway to promote apoptosis in chronic prostatitis. Int Immunopharmacol. 2025;151:114332. https://doi.org/10.1016/j.intimp.2025.114332
24. Wang J, Zhang B, Jiao Y, et al. Involvement of prostatic interstitial cells of Cajal in inflammatory cytokines-elicited catecholamines production: implications for the pathophysiology of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Biochem Biophys Res Commun. 2018;503(2):420-427. https://doi.org/10.1016/j.bbrc.2018.04.050
25. Shankar E, Vykhovanets EV, Vykhovanets OV, et al. High-fat diet activates pro-inflammatory response in the prostate through association of Stat-3 and NF-κB. Prostate. 2012;72(3):233-243. https://doi.org/10.1002/pros.21425
26. Ho CH, Lu YC, Fan CK, et al. Testosterone regulates the intracellular bacterial community formation of uropathogenic Escherichia coli in prostate cells via STAT3. Int J Med Microbiol. 2020;310(7):151450. https://doi.org/10.1016/j.ijmm.2020.151450
27. Yenigun A. The efficacy of tonsillectomy in chronic tonsillitis patients as demonstrated by the neutrophil-to-lymphocyte ratio. J Laryngol Otol. 2015;129(4):386-391. https://doi.org/10.1017/S0022215115000559
28. Ding Y, Koh JH, Cheah XY, et al. Serum biomarkers after adenotonsillectomy for pediatric OSA: a systematic review and meta-analysis. Laryngoscope. 2024;134(7):3030-3037. https://doi.org/10.1002/lary.31249
29. Agarwal A, Rana M, Qiu E, et al. Role of oxidative stress, infection and inflammation in male infertility. Andrologia. 2018;50(11):e13126. https://doi.org/10.1111/and.13126
30. Fomichova O, Oliveira PF, Bernardino RL. Exploring the interplay between inflammation and male fertility. FEBS J. 2025;292(13):3321-3349. https://doi.org/10.1111/febs.17366
31. Lustig L, Guazzone VA, Theas MS, et al. Pathomechanisms of autoimmune based testicular inflammation. Front Immunol. 2020;11:583135. https://doi.org/10.3389/fimmu.2020.583135
32. Silva CA, Cocuzza M, Carvalho JF, Bonfá E. Diagnosis and classification of autoimmune orchitis. Autoimmun Rev. 2014;13(4-5):431-434. https://doi.org/10.1016/j.autrev.2014.01.024
33. Zhang H, Yin Y, Wang G, et al. Interleukin-6 disrupts blood-testis barrier through inhibiting protein degradation or activating phosphorylated ERK in Sertoli cells. Sci Rep. 2014;4:4260. https://doi.org/10.1038/srep04260
34. Pérez CV, Sobarzo CM, Jacobo PV, et al. Loss of occludin expression and impairment of blood-testis barrier permeability in rats with autoimmune orchitis: effect of interleukin 6 on Sertoli cell tight junctions. Biol Reprod. 2012;87(5):122. https://doi.org/10.1095/biolreprod.112.101709
35. Wang F, Liu W, Jiang Q, et al. Lipopolysaccharide-induced testicular dysfunction and epididymitis in mice: a critical role of tumor necrosis factor alpha. Biol Reprod. 2019;100(3):849-861. https://doi.org/10.1093/biolre/ioy235
36. Hasan H, Bhushan S, Fijak M, Meinhardt A. Mechanism of inflammatory associated impairment of sperm function, spermatogenesis and steroidogenesis. Front Endocrinol. 2022;13:897029. https://doi.org/10.3389/fendo.2022.897029
37. Aguirre Morgado NP, Pereira Suárez AL, Chabay P, et al. Tonsillar microbial signature of Fusobacterium nucleatum associated with Epstein-Barr virus latency. J Med Virol. 2026;98(1):e70808. https://doi.org/10.1002/jmv.70808
38. Jiang SS, Chen YX, Fang JY. Fusobacterium nucleatum: ecology, pathogenesis and clinical implications. Nat Rev Microbiol. 2025. https://doi.org/10.1038/s41579-025-01237-z
39. Kurpisz M, Alexander NJ. Carbohydrate moieties on sperm surface: physiological relevance. Fertil Steril. 1995;63(1):158-165. https://doi.org/10.1016/S0015-0282(16)57312-9
40. Archana SS, Selvaraju S, Binsila BK, Arangasamy A, Krawetz SA. Immune regulatory molecules as modifiers of semen and fertility: a review. Mol Reprod Dev. 2019;86(11):1485-1504. https://doi.org/10.1002/mrd.23263
41. Cui JJ, Zhong W, Zhang YQ, et al. Prevalence of semen abnormalities and the impact of genital pathogens on male infertility: a retrospective analysis of 131 183 patients. Asian J Androl. 2026. https://doi.org/10.4103/aja20264
42. Chen L, Chen Z, Chen J, et al. CXCL10 promotes spinal macrophage recruitment via the JAK/STAT3 pathway to induce pain in experimental autoimmune prostatitis. Cell Prolif. 2025;58(4):e13784. https://doi.org/10.1111/cpr.13784
43. Gur C, Ibrahim Y, Isaacson B, et al. Binding of the Fap2 protein of Fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack. Immunity. 2015;42(2):344-355. https://doi.org/10.1016/j.immuni.2015.01.010
44. Schöpf F, Marongiu GL, Milaj K, et al. Structural basis of Fusobacterium nucleatum adhesin Fap2 interaction with receptors on cancer and immune cells. Nat Commun. 2025;16(1):8104. https://doi.org/10.1038/s41467-025-63451-w
45. Wuyi W, Tao P. Microbe-driven immune suppression in colorectal cancer: the Fusobacterium nucleatum playbook. Front Immunol. 2026;17:1795703. https://doi.org/10.3389/fimmu.2026.1795703
46. Luo W, Han J, Peng X, et al. The role of Fusobacterium nucleatum in cancer and its implications for clinical applications. Mol Oral Microbiol. 2024;39(6):417-432. https://doi.org/10.1111/omi.12475
47. Blessin NC, Simon R, Kluth M, et al. Patterns of TIGIT expression in lymphatic tissue, inflammation, and cancer. Dis Markers. 2019;2019:5160565. https://doi.org/10.1155/2019/5160565
48. Norström MM, Rådestad E, Sundberg B, et al. Progression of benign prostatic hyperplasia is associated with pro-inflammatory mediators and chronic activation of prostate-infiltrating lymphocytes. Oncotarget. 2016;7(17):23581-23593. https://doi.org/10.18632/oncotarget.8051
49. Sfanos KS, Bruno TC, Meeker AK, et al. Human prostate-infiltrating CD8+ T lymphocytes are oligoclonal and PD-1+. Prostate. 2009;69(15):1694-1703. https://doi.org/10.1002/pros.21020
50. Adorno Febles VR, Hao Y, Ahsan A, et al. Single-cell analysis of localized prostate cancer patients links high Gleason score with an immunosuppressive profile. Prostate. 2023;83(9):840-849. https://doi.org/10.1002/pros.24524
51. Chen L, Bian Z, Chen J, et al. Immunological alterations in patients with chronic prostatitis/chronic pelvic pain syndrome and experimental autoimmune prostatitis model: a systematic review and meta-analysis. Cytokine. 2021;141:155440. https://doi.org/10.1016/j.cyto.2021.155440
52. Motrich RD, Breser ML, Molina RI, et al. Patients with chronic prostatitis/chronic pelvic pain syndrome show T helper type 1 (Th1) and Th17 self-reactive immune responses specific to prostate and seminal antigens and diminished semen quality. BJU Int. 2020;126(3):379-387. https://doi.org/10.1111/bju.15117
53. Du HX, Yue SY, Niu D, et al. Gut microflora modulates Th17/Treg cell differentiation in experimental autoimmune prostatitis the short-chain fatty acid propionate. Front Immunol. 2022;13:915218. https://doi.org/10.3389/fimmu.2022.915218
54. Meng HX, Ohe R, Li HN, et al. Immunoglobulin and CD8⁺ T-cell distribution in histologically distinctive tonsils of individuals with tonsillar focal infection. Acta Otolaryngol. 2015;135(3):264-270. https://doi.org/10.3109/00016489.2014.968802
55. Thumbikat P, Pattabiraman G, Sharifzad F, et al. Epigenetic regulation of immune dysfunction in chronic prostatitis/chronic pelvic pain syndrome. Prostate. 2026. https://doi.org/10.1002/pros.70191
56. Nesheim N, Ellem S, Dansranjavin T, et al. Elevated seminal plasma estradiol and epigenetic inactivation of ESR1 and ESR2 is associated with CP/CPPS. Oncotarget. 2018;9(28):19623-19639. https://doi.org/10.18632/oncotarget.24714
57. Liu J, Wang Y, Zhang G, Liu L, Peng X. Multi-omics analysis reveals changes in the intestinal microbiome, transcriptome, and methylome in a rat model of chronic non-bacterial prostatitis: indications for the existence of the gut-prostate axis. Front Physiol. 2021;12:753034. https://doi.org/10.3389/fphys.2021.753034
58. Done JD, Rudick CN, Quick ML, Schaeffer AJ, Thumbikat P. Role of mast cells in male chronic pelvic pain. J Urol. 2012;187(4):1473-1482. https://doi.org/10.1016/j.juro.2011.11.116
59. Pattabiraman G, Engel G, Osborn CV, et al. Efficacy of targeted mast cell inhibition therapy in chronic prostatitis/chronic pelvic pain syndrome. Urology. 2023;180:200-208. https://doi.org/10.1016/j.urology.2023.05.047
60. Cheng B, Gong L, Xu H, et al. The microbiome across the prostate disease continuum: from health and BPH to prostatitis/CPPS and cancer. Oncogene. 2026;45(21):1955-1969. https://doi.org/10.1038/s41388-026-03815-8
61. Song S, Zhang C, Zhang B, et al. Targeting the brain-gut-prostate axis in chronic prostatitis: mechanisms and therapeutics. Front Endocrinol. 2025;16:1628094. https://doi.org/10.3389/fendo.2025.1628094
62. Osmancevic A, Daka B, Michos ED, Trimpou P, Allison M. The association between inflammation, testosterone and SHBG in men: a cross-sectional multi-ethnic study of atherosclerosis. Clin Endocrinol. 2023;99(2):190-197. https://doi.org/10.1111/cen.14930
63. Hsu CY, Jasim SA, Pallathadka H, et al. A comprehensive insight into the contribution of epigenetics in male infertility; focusing on immunological modifications. J Reprod Immunol. 2024;164:104274. https://doi.org/10.1016/j.jri.2024.104274
64. Cui Y, Deng J, Zhang Y, et al. Epigenetic regulation by DNA methylation, histone modifications and chromatin remodeling complexes in controlling spermatogenesis and their dysfunction with male infertility. Cell Mol Life Sci. 2025;82(1):343. https://doi.org/10.1007/s00018-025-05831-5
65. Rajender S, Avery K, Agarwal A. Epigenetics, spermatogenesis and male infertility. Mutat Res. 2011;727(3):62-71. https://doi.org/10.1016/j.mrrev.2011.04.002
66. Rotondo JC, Lanzillotti C, Mazziotta C, Tognon M, Martini F. Epigenetics of male infertility: the role of DNA methylation. Front Cell Dev Biol. 2021;9:689624. https://doi.org/10.3389/fcell.2021.689624
67. Sudhakaran G, Kesavan D, Kandaswamy K, Guru A, Arockiaraj J. Unravelling the epigenetic impact: oxidative stress and its role in male infertility-associated sperm dysfunction. Reprod Toxicol. 2024;124:108531. https://doi.org/10.1016/j.reprotox.2023.108531
68. Ji J, Sundquist J, Sundquist K. Tonsillectomy associated with an increased risk of autoimmune diseases: a national cohort study. J Autoimmun. 2016;72:1-7. https://doi.org/10.1016/j.jaut.2016.06.007
69. Chi HW, Su CH, Wang YH, et al. Surgical removal of Waldeyer's ring and long-term risk of Sjögren's syndrome: a population-based cohort study investigating the mucosal immune link. Front Immunol. 2026;17:1760386. https://doi.org/10.3389/fimmu.2026.1760386
70. Chen Z, Zhang E, Liu N, Tao T, Huang G. Relationship between infection or inflammation of prostate and risk of prostate cancer: a cross-sectional population-based study. Eur J Med Res. 2026;31:191. https://doi.org/10.1186/s40001-025-03717-7
71. Krishna M, Garg P, Horne D, Salgia R, Singhal SS. Inflammation-driven transcriptional reprogramming in prostate cancer: convergence of NFκB, JAK/STAT3, and epigenetic remodeling in castration-resistant disease. Cancer Lett. 2026;655:218647. https://doi.org/10.1016/j.canlet.2026.218647
72. de Bono JS, Guo C, Gurel B, et al. Prostate carcinogenesis: inflammatory storms. Nat Rev Cancer. 2020;20(8):455-469. https://doi.org/10.1038/s41568-020-0267-9
73. Xiao X, Yang F, Yin L, et al. Stress-related disorders among young individuals with surgical removal of tonsils or adenoids. JAMA Netw Open. 2024;7(12):e2449807. https://doi.org/10.1001/jamanetworkopen.2024.49807
74. Quagliariello V, Forte P, Ciappina G, et al. Fusobacteriumnucleatum: pathophysiological and clinical involvement in inflammatory bowel diseases, colorectal cancer and cardiovascular diseases. Cancers. 2025;17(20):3348. https://doi.org/10.3390/cancers17203348
75. Kitamoto S, Kamada N. Periodontal connection with intestinal inflammation: microbiological and immunological mechanisms. Periodontol 2000. 2022;89(1):142-153. https://doi.org/10.1111/prd.12424
76. Ohashi A, Murayama MA, Miyabe Y, Yudoh K, Miyabe C. Streptococcal infection and autoimmune diseases. Front Immunol. 2024;15:1361123. https://doi.org/10.3389/fimmu.2024.1361123
77. Márquez-Arrico CF, Silvestre FJ, Fernández-Reyes M, Silvestre-Rangil J, Rocha M. Is there an association between periodontal disease and infertility? A systematic review. Med Oral Patol Oral Cir Bucal. 2024;29(6):e866-e875. https://doi.org/10.4317/medoral.26831
78. Tao DY, Zhu JL, Xie CY, et al. Relationship between periodontal disease and male infertility: a case-control study. Oral Dis. 2021;27(3):624-631. https://doi.org/10.1111/odi.13552
79. Isola G, Santonocito S, Lupi SM, et al. Periodontal health and disease in the context of systemic diseases. Mediators Inflamm. 2023;2023:9720947. https://doi.org/10.1155/2023/9720947
80. Wetzel C, Bumm CV, Becker J, et al. Infertility and periodontitis: are we connecting the right dots? J Dent Res. 2026. https://doi.org/10.1177/00220345261416502
81. Han YW. Fusobacterium nucleatum: a commensal-turned pathogen. Curr Opin Microbiol. 2015;23:141-147. https://doi.org/10.1016/j.mib.2014.11.013
82. Bazzar B, Reshadfar E, Namdar P, et al. The relationship between seminal microbiome and male reproductive wellness: a systematic review. Biol Reprod. 2026;114(4):1151-1167. https://doi.org/10.1093/biolre/ioag003
83. Chen T, Zhang B, He G, et al. Gut-derived exosomes mediate the microbiota dysbiosis-induced spermatogenesis impairment by targeting Meioc in mice. Adv Sci. 2024;11(22):e2310110. https://doi.org/10.1002/advs.202310110
84. Zheng JC, Jin ZR, Liu BH, et al. Chronic stress drives oligoasthenozoospermia via gut microbiota-vitamin-Sting1/Slc9c2 axis. Nat Commun. 2026;17(1):4108. https://doi.org/10.1038/s41467-026-72450-4
85. Moretti E, Figura N, Campagna MS, et al. Infectious burden and semen parameters. Urology. 2017;100:90-96. https://doi.org/10.1016/j.urology.2016.10.032
86. Tremellen K, McPhee N, Pearce K, et al. Endotoxin-initiated inflammation reduces testosterone production in men of reproductive age. Am J Physiol Endocrinol Metab. 2018;314(3):E206-E213. https://doi.org/10.1152/ajpendo.00279.2017
87. Reichlin S. Neuroendocrine-immune interactions. N Engl J Med. 1993;329(17):1246-1253. https://doi.org/10.1056/NEJM199310213291708
88. De Silva NL, Papanikolaou N, Grossmann M, et al. Male hypogonadism: pathogenesis, diagnosis, and management. Lancet Diabetes Endocrinol. 2024;12(10):761-774. https://doi.org/10.1016/S2213-8587(24)00199-2
89. Maffezzoni F, Porcelli T, Delbarba A, et al. Hypogonadism and bone health in men with HIV. Lancet HIV. 2020;7(11):e782-e790. https://doi.org/10.1016/S2352-3018(20)30236-8

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