High risk and low prevalence diseases: Testicular torsion.

INTRODUCTION: Testicular torsion is a serious condition that carries with it a high rate of morbidity. OBJECTIVE: This review highlights the pearls and pitfalls of testicular torsion, including presentation, diagnosis, and management in the emergency department (ED) based on current evidence. DISCUSSION: Testicular torsion is a urological emergency that occurs with rotation of the testicle along its supporting ligaments leading to obstruction of vascular flow. A key risk factor is the presence of a bell-clapper deformity. The most common population affected includes children in a bimodal distribution with the most cases occurring in the first year of life and between 12 and 18 years, although cases do occur in adults. Acute, severe, unilateral scrotal pain is the most common presenting symptom. Nausea and vomiting are common, but the presence or absence of a cremasteric reflex is not a reliable indicator of disease. The TWIST score may assist with clinical decision making in patients presenting with acute testicular pain but should not be used in isolation. If torsion is suspected or confirmed, consultation with the urology specialist should not be delayed, as outcomes are time sensitive. Ultrasound can be used for diagnosis, but a normal ultrasound examination cannot exclude the diagnosis. Treatment includes emergent urology consultation for surgical exploration and detorsion, as well as symptomatic therapy in the ED. Manual detorsion can be attempted in the ED while awaiting transfer or consultation. CONCLUSIONS: An understanding of testicular torsion can assist emergency clinicians in diagnosing and managing this disease.

Postvaricocele Embolization Pain Syndrome: A Case Series Report and Review of Current Treatment Strategies.

BACKGROUND: Orchialgia is not an uncommon complaint among men with varicocele, but postvaricocele embolization-related testicular pain has not been widely investigated. This study evaluates the phenomenon of postvaricocele embolization pain (PVEP) syndrome and examines the current strategies to treat this unusual complication. METHODS AND MATERIALS: A prospectively collected database of patients with PVEP who presented to a tertiary center was analyzed between January 2011 and January 2020 following internal ethics approval. Patient demographics, including other complications related to embolization, analgesic requirements, and pain scores (on a 10-point visual analog score), treatment strategies, Patient Global Impression of Improvement (PGI-I) score and overall satisfaction score (on a 5-point scale), were reviewed. All patients were reviewed for a minimum of 12 months. RESULTS: A total of 20 men with a mean age of 33.8 (18-45) years old, presented with PVEP over 10 years. Most men received embolization on an average of 26.6 (18-48) months. The reasons for varicocele embolization include either isolated or combined orchialgia (15 men), subfertility (5 men), and cosmesis (6 men). Eighteen (90%) men underwent microscopic spermatic cord denervation (MSCD) and 2 patients elected for conservative measures. The average pain scores pre-MSCD and post-MSCD were 6.9 (4-9) and 1.4 (0-4) (p<0.001) with a significant reduction in analgesia requirements. Immediate improvement in pain score was reported in all the patients and this persisted at the 12 months review. Most men reported a high satisfaction score (of 4/5) and only one patient reported no change in symptoms after MSCD. CONCLUSION: PVEP is a unique complication and patients should be counseled on the potential risk of persistent orchialgia following embolization for varicocele. The MSCD appears to be an effective treatment option with high success and satisfaction rates.

Testicular schistosomiasis: a systematic review of the literature.

INTRODUCTION: To consolidate reported information on presentation, diagnosis, and treatment modalities in testicular schistosomiasis (TS) to provide a reference tool for this rare disease. MATERIALS AND METHODS: A comprehensive PubMed search was performed using PRISMA guidelines, which yielded 21 articles detailing 22 cases of TS. RESULTS: Testicular schistosomiasis remains a rare disease, presenting at a variety of ages (median age 27). All reports of this condition are associated with exposure to an endemic area. The most common presenting symptoms include nonspecific testicular swelling (54.5%) followed by a testicular mass/nodule (18.4%). Diagnosis relies upon clinical suspicion due to low specificity on laboratory and imaging evaluation, with only 18% of urine evaluations positive for parasitic infection. Final diagnosis was made on biopsy (38.1%), radical orchiectomy (47.6%) or frozen section during partial orchiectomy (14.3%). Treatment included anthelmintic mediation (37%), radical/partial orchiectomy (31%), or some combination of the above. CONCLUSIONS: This systematic review of individual patient data reveals that while urine tests and imaging may aid in diagnosis, all patients require definitive histologic diagnosis. It is important to obtain a thorough history to elucidate exposure to endemic areas and inform whether biopsy, and subsequent testicular preservation, may be appropriate.

[Chronic testicular pain: A multidisciplinary challenge]. / Douleurs testiculaires chroniques : un défi multidisciplinaire.

Chronic testicular pain represents up to 5% of urological consultations. A simple workup can help identify an organic etiology in 50 to 75% of cases, leading to a targeted treatment. If this is not the case, chronic idiopathic orchialgia is diagnosed and multidisciplinary management is necessary. Treatment is initially conservative but is only effective in 4 to 15% of patients. Spermatic block by infiltration of the cord confirms the testicular origin of the pain and provides temporary relief. Microsurgical denervation of the spermatic cord is the treatment of choice for responders. It provides significant pain relief in 77 to 100% of cases.

Les douleurs testiculaires chroniques représentent jusqu'à 5 % des consultations d'urologie. Un bilan simple retrouve une étiologie organique dans 50 à 75 % des cas permettant un traitement ciblé. Le cas échéant, le diagnostic d'exclusion d'orchialgie chronique idiopathique est retenu et une prise en charge multidisciplinaire est alors nécessaire. Le traitement est initialement conservateur, mais n'est efficace que chez 4 à 15 % des patients. La réalisation d'un bloc spermatique par infiltration du cordon permet de confirmer l'origine testiculaire des douleurs et apporte un soulagement temporaire. La dénervation microchirurgicale du cordon spermatique est le traitement de choix pour les répondeurs. Il permet un soulagement significatif des douleurs dans 77 à 100 % des cas.

Management of Testicular Microlithiasis.

Until molecular diagnostics become available, individualized risk assessment for men with testicular microlithiasis, counseling on the current evidence base regarding the benefit of testicular biopsy or testicular self-examination, and a patient-centered approach provide the framework for the best quality of care for the individual patient.

Leech therapy (Hirudo medicinalis) attenuates testicular damages induced by testicular ischemia/reperfusion in an animal model.

BACKGROUND: Testicular torsion/detorsion triggers tissue ischemia/reperfusion, leading to reactive oxygen species overgeneration and apoptosis. The saliva of leeches is full of anti-inflammatory, anticoagulants, antioxidants, and antimicrobial agents. Therefore, this study aimed to assess the protective mechanism of leech therapy on testicular ischemia/reperfusion damage. METHODS: 18 adult male rats were randomly divided into three groups: 1-Sham-operated group (SO). 2-Torsion/detorsion (T.D) group: two hours of testicular torsion with two hours of testicular detorsion was performed. 3-Torsion/detorsion + Leech therapy (TDL) group. Sperm parameters (motility, vitality, morphology, and concentration), oxidative stress biomarkers (MDA, CAT, GPx, and TAC), histopathological factors (Mean seminiferous tubular diameter, Germinal epithelial cell thickness, Testicular capsule thickness, Johnson's score, and Cosentino's score), and immunohistochemical markers for apoptosis detection (Bax, Bcl-2, and Caspase-3) were measured. RESULTS: There was a significant difference for all sperm parameters in the T. D group compared to the sham group. Leech therapy significantly increased progressive motility and normal morphology and reduced non-progressive motility. In the TDL group, MDA concentration significantly reduced, and levels of GPx, TAC, and CAT remarkably increased. All evaluated histopathological parameters in the TDL group significantly increased compared to the T. D group except for the testicular capsule thickness. T. D notably increased the expression of Bax and Caspase-3, while the treatment group slowed the rate of apoptosis compared to the control group. Bcl-2 expression in the T. D group was significantly lower than that in the sham group. Leech therapy increased the Bcl-2 expression. CONCLUSION: Leech therapy attenuates damages to testicular tissue following torsion/detorsion due to its antioxidant, anti-inflammatory, and anti-apoptotic effects. Hence, it can be considered as an effective remedy for testicular ischemia/reperfusion.

Spermatic Cord Block Series as a Minimally Invasive Therapy for Chronic Scrotal Content Pain.

PURPOSE: The primary aim of our study was to evaluate relief of chronic scrotal content pain after a series of spermatic cord blocks with a combination of local anesthetic and a steroid. Secondary aims were to assess factors associated with a positive response and complications. MATERIALS AND METHODS: We performed a retrospective chart review of patients who underwent spermatic cord block series for chronic scrotal content pain at our practice between 2012 and 2019. Pain scores were compared before and after treatment using an 11-point numerical pain rating scale. We performed univariate analysis to assess differences between responders and nonresponders, and the relationship between symptom duration and response was analyzed by rank-order correlation. RESULTS: We included 44 men with chronic scrotal content pain present for a median duration of 24 months who underwent a spermatic cord block series. At a median followup of 16 months, 31 patients (70.5%) experienced sustained relief, including 9 patients (20.5%) with complete resolution of pain. There were no differences between responders and nonresponders in terms of symptom duration, perceived etiology, or previous treatments, and there was no association between response and duration of pain. Minor complications occurred in 5 cases (11.4%). CONCLUSIONS: Spermatic cord block series is a safe, minimally invasive treatment for men with refractory chronic scrotal content pain. Response to cord block series appears to be independent of symptom duration, perceived etiology or prior medical and surgical treatments. Future studies should be conducted to evaluate long-term durability and predictors of success.

Chronic Scrotal Content Pain: a Review of the Literature and Management Schemes.

PURPOSE OF REVIEW: Chronic scrotal content pain (CSCP) is a complex condition with multiple etiologies that requires a thorough understanding of its pathophysiology, workup, and treatment options. We performed a comprehensive and contemporary review to augment our current understanding of CSCP. RECENT FINDINGS: We discuss new advances in CSCP-specific pain questionnaires, modern studies of microscopic spermatic cord denervation and its variations, and novel techniques including electric nerve stimulation and cryoablation in addition to randomized control trials with significant negative findings. We also present literature focusing on the prevention of CSCP secondary to surgical iatrogenic causes. The constantly evolving literature of CSCP has led to the significant evolution in its diagnosis and treatment, from oral medications to salvage options after microscopic spermatic cord denervation. With each advance, we come closer to developing a more thorough, evidence-based algorithm to guide urologists in treatment of CSCP.

Male infertility due to testicular disorders.

CONTEXT: Male infertility is defined as the inability to conceive following 1 year of regular unprotected intercourse. It is the causative factor in 50% of couples and a leading indication for assisted reproductive techniques (ART). Testicular failure is the most common cause of male infertility, yet the least studied to date. EVIDENCE ACQUISITION: The review is an evidence-based summary of male infertility due to testicular failure with a focus on etiology, clinical assessment, and current management approaches. PubMed-searched articles and relevant clinical guidelines were reviewed in detail. EVIDENCE SYNTHESIS/RESULTS: Spermatogenesis is under multiple levels of regulation and novel molecular diagnostic tests of sperm function (reactive oxidative species and DNA fragmentation) have since been developed, and albeit currently remain as research tools. Several genetic, environmental, and lifestyle factors provoking testicular failure have been elucidated during the last decade; nevertheless, 40% of cases are idiopathic, with novel monogenic genes linked in the etiopathogenesis. Microsurgical testicular sperm extraction (micro-TESE) and hormonal stimulation with gonadotropins, selective estrogen receptor modulators, and aromatase inhibitors are recently developed therapeutic approaches for men with the most severe form of testicular failure, nonobstructive azoospermia. However, high-quality clinical trials data is currently lacking. CONCLUSIONS: Male infertility due to testicular failure has traditionally been viewed as unmodifiable. In the absence of effective pharmacological therapies, delivery of lifestyle advice is a potentially important treatment option. Future research efforts are needed to determine unidentified factors causative in "idiopathic" male infertility and long-term follow-up studies of babies conceived through ART.

Challenges in the diagnosis of testicular infarction in the presence of prolonged epididymitis: Three cases report and literature review.

INTRODUCTION: Testicular infarction is a rare complication of prolonged epididymitis and may be misdiagnosed as testicular torsion. In this study, we present three cases of testicular infarction and discuss their clinical characteristics, imaging features and clinical management. PATIENTS AND METHODS: Three adult males with prolonged epididymitis presented with chronic unilateral testicular pain, tenderness, and palpable swelling, including left varicocele in one case and hydrocele in the other two cases. Patient's symptoms were not relieved after antibiotic therapy. We analyzed the diagnosis, management, and outcome of these three cases of testicular infarction resulting from prolonged epididymitis. This includes the clinical characteristics, features of color doppler ultrasound imaging for diagnosis, and treatment strategy for testicular infarction from prolonged epididymitis. RESULTS: Complete blood count (CBC) indicated a small leukocytosis (10.6±0.4×109/L; normal arrange 3.5-9.5 WBC×109/L). Color doppler images demonstrated appropriate blood flow to areas of interest at patient's initial visit. At follow up visit several months later, the increased blood flow was detected at the edges of the involved testes with no blood flow to the center. The sizes of the involved testis (27±4 ml) was significantly larger compared to the non affected side (17±2 ml) (p < 0.05). Unilateral simple orchiectomy was performed on the involved testis in all three cases. Grossly, abscess cavities with caseous necrosis were found at the center of the testicle and epididymis in two patients. Histopathologic examination showed chronic inflammation with lymphocytic and macrophage infiltration of the involved testicle in two cases. The third case stained positive for acid fast bacteria. Left varicocele disappeared postoperatively in one patient. No pain, wound infection or other discomfort were noted 12 months after surgery. COMMENTS: This series revealed that testicular infarction may result from inappropriately treated prolonged epididymitis. Epididymal tuberculosis should be considered in cases with epididymitis not responding to broad spectrum antibiotics. Testicular infarction induced by prolonged epididymitis is easily missed due to a lack of symptom changes. Color doppler images are helpful in the diagnosis. This usually presents as a decrease in blood flow at the center of the testis with the increased flow at the periphery differentiating this from testicular torsion.

Cystic Dysplasia of the Rete Testis: Does Pathophysiology Guide Management?

Cystic dysplasia of the rete testis (CDT) is a rare, benign, cause of testicular mass in the pediatric population. The mass appears on sonography as multiple small cysts of varying size surrounded by normal or compressed testicular tissue. CDT is often associated with other genitourinary anomalies, commonly presenting with agenesis or dysplasia of the ipsilateral kidney. The pathophysiology and the management remains controversial. We report a case of a 3-year-old presenting with an enlarged testicular mass later presumed to be CDT associated with ipsilateral renal agenesis, review the literature, and propose an evaluation and management algorithm.

The clinical features and treatment options of intratesticular epidermoid cysts. / Las características clínicas y opciones de tratamiento de los quistes epidermoides intratesticulares.

OBJECTIVES: In this study, we aimed to define the clinico-radiological data and treatment options for intratesticular epidermoid cysts (IEC). MATERIALS AND METHODS: We retrospectively reviewed the medical records of the patients that under went surgery for testicular mass between 1995 and 2017. Data of the patients whose histopathological evaluation revealed IEC were recorded.  RESULTS: A total of 20 patients with IEC were identified.While three of 20 patients were excluded due to incomplete data, the remaining 17 patients with pathologically proven IEC were reviewed and analyzed in the study. The mean patient age was 22.2 years (range, 17-29 years). All patients were presented with painless testicular swelling and/or mass. Serum tumor markers of all patients were within the ranges. Four patients treated with radical orchiectomy (23.5%), while 13 patients under went partial orchiectomy (76.5%). The mean size ofthe IEC was 17.7x15.1 mm (range, 26x10 mm). IEC swere mostly located in the middle pole of the testes (10of 17 patients, 58.8%). CONCLUSIONS: This study is designed in retrospective nature, but the patient population is one the largest reported in the literature. According to our study, we can easily state that partial orchiectomy can be performed safely after FSA in patients that have IECs.

OBJETIVOS: En este estudio, nuestro objetivofue definir los datos clínico-radiológicos y las opciones de tratamiento de los quistes epidermoides intratesticulares (CEI). MATERIALES Y MÉTODOS: Revisamos retrospectivamente los registros médicos de los pacientes que se sometieron a cirugía para la masa testicular entre 1995 y 2017. Entre ellos se registraron los datos de los pacientes cuya evaluación histopatológica reveló IEC. RESULTADOS: Se identificaron un total de 20 pacientes con IEC. Mientras que tres de los 20 pacientes fueron excluidos debido a los datos incompletos, los 17pacientes restantes con IEC patológicamente probada se revisaron y analizaron en el estudio. La edad media de los pacientes fue de 22,2 años (rango, 17-29años). A todos los pacientes se les presentó hinchazón y/o masa testicular indolora. Los marcadores tumorales séricos de todos los pacientes estaban dentro de los rangos. Cuatro pacientes tratados con orquiectomía radical (23,5%), mientras que 13 pacientes se sometieron a orquiectomía parcial (76,5%). El tamaño medio de la IEC fue de 17,7x15,1 mm (rango, 26x10 mm). Los IEC se encontraban principalmente en el polo medio de los testículos (10 de 17 pacientes, 58,8%). CONCLUSIONES: Este estudio está diseñado de forma retrospectiva, pero la población de pacientes es una de las más numerosas que se han publicado en la literatura. Según nuestro estudio, podemos afirmar fácilmente que la orquiectomía parcial se puede realizar de manera segura después de la FSA en pacientes que tienen CEI.

Rare benign and malignant testicular lesions: histopathology and management.

PURPOSE OF REVIEW: The presence of vascular solid tumors within the testicle is considered to be malignant until proven otherwise. However, it is prudent for clinicians to be aware of rare benign and malignant intratesticular lesions as management can differ from the established treatment algorithms for germ-cell tumors. RECENT FINDINGS: Utilizing certain histopathologic findings can assist with the diagnosis of rare testis tumors. Often times the tumor subtypes are an important consideration in the grading and classification of the disease, which drives management. The multidisciplinary management of rare malignant testis tumors at an experienced center seems to provide optimal patient outcomes. Regardless of the primary treatment, prolonged follow-up for sex cord stromal tumors and other rare testis malignancies is advocated due to the delayed metastatic potential. SUMMARY: The clinical presentation of rare benign and malignant testis tumors is often similar to that of germ-cell tumors. Likewise, imaging characteristics are also often indistinguishable. However, the management of these rare tumors is often different from the well established treatment algorithms of germ-cell tumors. To that end, it is important for the practicing urologist to be familiar with the current principles of these tumor characteristics and the management.

Aspiration and sclerotherapy of hydroceles and spermatoceles/epididymal cysts with 100% alcohol.

OBJECTIVE: To evaluate the efficacy of aspiration and sclerotherapy with 100% alcohol for the primary treatment of benign scrotal cysts. METHODS: From March 2014 to March 2018, 114 patients were identified who underwent their first aspiration and sclerotherapy procedure (80 hydroceles and 34 spermatoceles/epididymal cysts). The procedure was carried out in the outpatient clinic with local anaesthesia. A 16-gauge IV catheter is used to puncture the sac under aseptic conditions. The volume of alcohol instilled was 10% of the aspirated volume (maximum of 50 mL). Patients were then observed in the waiting room and completed a questionnaire. Urology clinic follow up was scheduled at 6 weeks. RESULTS: At follow up, 54 patients (67.5%) with hydroceles and 25 patients (73.5%) with spermatoceles/epididymal cysts had resolution after a single procedure. A second procedure was offered if fluid collection persisted, of which 71% of patients with hydroceles and 100% of patients with spermatoceles/epididymal cysts had a successful outcome. At a median of 31 months post-initial procedure, the overall success rate, after at most two procedures, was 80% for hydroceles and 85% for spermatoceles/epididymal cysts. The complication rate was low (6%). Almost all patients were happy to undergo the procedure again, if needed. Persistence following aspiration and sclerotherapy were more likely to occur in younger patients (45.4 versus 61.2 years, P = 0.001). Persistence was not related to the volume of fluid aspirated. CONCLUSION: Aspiration and sclerotherapy with alcohol is a reliable, safe and effective technique for treatment of benign scrotal cysts.

A Randomized, Double-Blind, Controlled Trial Shows that Onabotulinum Toxin A Nerve Blocks do Not Provide Improved Pain Control in Men with Chronic Scrotal Pain.

PURPOSE: The use of onabotulinum toxin A to chemically denervate the testis has been studied as a minimally invasive therapy to treat chronic scrotal pain. To our knowledge no randomized, controlled trials of onabotulinum toxin A for chronic scrotal pain management have been reported to date. MATERIALS AND METHODS: In this double-blind, randomized, controlled trial men with chronic scrotal pain who achieved at least temporary pain relief following a cord block with local anesthesia were randomly assigned to a block using local anesthesia alone vs local anesthesia plus 200 IU onabotulinum toxin A. Standardized assessments of pain levels using a visual analogue score, disease impact, quality of life and mood were performed 1, 2, 3, 4, 12 and 18 weeks after injection. The study primary outcome was the change in the visual analogue score at 1 month. After study completion the men in the control group were given the option to receive onabotulinum toxin A as part of an open label trial. RESULTS: Of 64 men with a mean ± SD age of 45.9 ± 11 years and a mean 5.7 ± 5.7-year history of pain 32 received local anesthesia plus onabotulinum toxin A and 32 received local anesthesia alone. There was no statistically significant difference in any measured outcome when comparing those who received onabotulinum toxin A to controls. Nine of the 13 men (69.2%) in the open label trial achieved an improvement in the visual analogue score (mean group score 6.1 ± 1.66 to 4.5 ± 2.36, Student t-test p=0.022) with a reduction in persistent pain at 3 months in 6 of the 9 (66.7%). CONCLUSIONS: This randomized, double-blind, controlled trial showed no superiority of onabotulinum toxin A plus local anesthesia over local anesthesia alone for pain control in men with chronic scrotal pain. Interestingly, significant pain improvement was noted in our open label onabotulinum toxin A trial, suggesting a potential placebo effect.

Acute Scrotal Emergencies.

Scrotal emergencies are rare but potentially life and fertility threatening. This article explains how to diagnose and manage scrotal emergencies such as testicular torsion, Fournier gangrene, and testicular trauma. These diagnoses are often difficult to discern from less-concerning causes. This article helps to elucidate the differences between the dangerous and the less-harmful pathologic conditions.

An Experimental Study to Evaluate the Protective Effects of Solanum lycopersicum Seed Essential Oil on Diabetes-Induced Testicular Injuries.

Background and Objectives: Diabetes is a chronic metabolic disorder that can effectively influences male reproductive performance. The present study was conducted to investigate the protective effects of Solanum lycopersicum essential oil (SL) on diabetes-induced testicular injuries. Materials and Methods: Adult male rats were randomly allocated into five groups (n = 8 in each group). 1: control; 2: diabetic; 3: diabetic + 30 mg/kg of SL essential oil; 4: diabetic + 90 mg/kg of SL essential oil; 5: diabetic + 270 mg/kg of SL essential oil extract. Diabetes was induced by a single dose of streptozotocin (55 mg/kg) intraperitoneally. Testicular changes were assessed quantitatively using stereological method followed by measuring antioxidant enzymes including catalase, superoxide dismutase, and glutathione peroxidase, and the serum testosterone level. Malondialdehyde (MDA) levels and Bcl-2expression were also evaluated in the tissue samples. Results: Diabetes resulted in significant deleterious changes in the structure of testicular tissue, suppressed antioxidant enzymes and testosterone levels, and increased lipid peroxidation. The expression of Bcl-2 was downregulated in diabetic testis and resulted in enhanced apoptosis. Following 8 weeks of treatment with SL essential oil, there were noticeable improvements in the structural changes of testis and the restoration of antioxidant defense and testosterone levels in testicular tissue, especially at higher doses. Conclusion: In conclusion, these findings reveal that the essential oil of Solanum lycopersicum has potent antioxidant properties and can attenuate the adverse effects of diabetes on male reproduction.

Testicular microlithiasis: Systematic review and Clinical guidelines.

INTRODUCTION: There are no clear recommendations on how patients with testicular microlithiasis should be followed up. The aim of our systematic review is to give clinical guidelines based on the evidence in the literature. METHODS: A web search was conducted during February 2018 based on Pubmed data, Embase and Cochrane database. The eligibility of articles was defined using the PICOS method, in concordance with the PRISMA recommendations. RESULTS: Fifty three articles were selected for our final synthesis. Our review highlighted an association between testicular microlithiasis and the already known risk factors of testicular germ cell tumor. The presence of testicular microlithiasis in patients with such risk factors increases more the risk of cancer. In the absence of risk factors, the risk to develop testicular cancer is similar to the risk in general population. CONCLUSION: In patients at risk to develop testicular cancer, observation versus testicular biopsy is debatable. We recommend an individualized approach based on the age of the patient, the presence of concurrent features of testicular dysgenesis syndrome, the fertility of the couple, the desire of paternity and the ultrasound pattern (bilateral and clustered vs. unilateral and limited).

Lactobacillus plantarum TW1-1 Alleviates Diethylhexylphthalate-Induced Testicular Damage in Mice by Modulating Gut Microbiota and Decreasing Inflammation.

Diethylhexylphthalate (DEHP), acting as an endocrine disruptor, disturbed reproductive health. Here, we evaluated the effects of Lactobacillus plantarum TW1-1 (L. plantarum TW1-1) on DEHP-induced testicular damage in adult male mice. Results showed that oral supplementation of L. plantarum TW1-1 significantly increased the serum testosterone concentration, enhanced the semen quality, and attenuated gonad development defects in DEHP-exposed mice. L. plantarum TW1-1 also alleviated DEHP-induced oxidative stress and inflammatory responses by decreasing the mRNA expression and serum protein concentration of different inflammatory factors [tumor necrosis factor-α, interleukin (IL)-1ß and IL-6]. Furthermore, L. plantarum TW1-1 significantly reduced DEHP-induced intestinal hyper-permeability and the increase in the serum lipopolysaccharide level. Gut microbiota diversity analysis revealed that L. plantarum TW1-1 shifted the DEHP-disrupted gut microbiota to that of the control mice. At phylum level, L. plantarum TW1-1 reversed DEHP-induced Bacteroidetes increase and Firmicutes decrease, and restored Deferribacteres in DEHP-exposed mice. Spearman's correlation analysis showed that Bacteroidetes, Deferribacteres, and Firmicutes were associated with DEHP-induced testicular damage. In addition, the ratio of Firmicutes to Bacteroidetes (Firm/Bac ratio) significantly decreased from 0.28 (control group) to 0.13 (DEHP-exposed group), which was restored by L. plantarum TW1-1 treatment. Correlation analysis showed that the Firm/Bac ratio was negatively correlated with testicular damage and inflammation. These findings suggest that L. plantarum TW1-1 prevents DEHP-induced testicular damage via modulating gut microbiota and decreasing inflammation.