Shuang-Ling Zou, Yi Zhang, Xin Yuan, Jia-Jie Li, Xin-Rui Sun, Xue Ma, Yi-Hong Yang, Fang Ma
{"title":"Epididymal extracellular vesicles: from intercellular communication to cellular development.","authors":"Shuang-Ling Zou, Yi Zhang, Xin Yuan, Jia-Jie Li, Xin-Rui Sun, Xue Ma, Yi-Hong Yang, Fang Ma","doi":"10.4103/aja20269","DOIUrl":"https://doi.org/10.4103/aja20269","url":null,"abstract":"<p><p>Sperm maturation in the epididymis is a complex and critical process that enables spermatozoa to acquire their motility and fertilizing ability. The epididymis is essential for sperm maturation and storage and provides a unique microenvironment to support these physiological processes. In recent years, epididymis-derived extracellular vesicles have attracted considerable attention for their role in controlling sperm quality. To date, the specific molecular mechanisms by which epididymal extracellular vesicles mediate sperm maturation remain inadequately elucidated. Several studies have hinted that extracellular vesicles mediate intercellular communication and cellular development, mainly through biomolecules such as transport proteins, lipids, and non-coding RNAs. This review constructs the framework of the molecular composition of epididymal vesicles and explores their potential functional implication in regulating sperm maturation. We also focus on the possible mechanisms through which these vesicles contribute to fertilization and early embryonic development and evaluate recent advances and application prospects of epididymal vesicles as biomarkers for male infertility.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148537952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gian Maria Busetto, Giovanni Barbieri, Piero Fischetti, Valeria Catalano, Federica De Luca, Valentina Camporeale, Marco Finati, Anna Ricapito, Angelo Cormio, Nicola d'Altilia, Ugo Giovanni Falagario, Luigi Cormio, Carlo Bettocchi, Giuseppe Carrieri, Elena Ranieri
{"title":"Multifunctional automated semen analysis system of global SDF and DSBs provides new insights into varicocele diagnosis.","authors":"Gian Maria Busetto, Giovanni Barbieri, Piero Fischetti, Valeria Catalano, Federica De Luca, Valentina Camporeale, Marco Finati, Anna Ricapito, Angelo Cormio, Nicola d'Altilia, Ugo Giovanni Falagario, Luigi Cormio, Carlo Bettocchi, Giuseppe Carrieri, Elena Ranieri","doi":"10.4103/aja202633","DOIUrl":"https://doi.org/10.4103/aja202633","url":null,"abstract":"<p><p>Varicocele is the most common cause of reversible male infertility. Although abnormalities in basic semen parameters are frequently observed, they offer limited value for assessing fertility potential. Elevated sperm DNA fragmentation (SDF) has been consistently reported in varicocele patients, but conventional SDF methods are hindered by technical complexity and poor standardization, limiting clinical usability. This study evaluated an automated platform integrating basic semen analysis, global SDF assessment (SCD-X12), and double-strand break (DSB) detection (SDFR-X12) for varicocele fertility assessment. Seventy varicocele patients and thirty normozoospermic controls were enrolled at the Department of Urology, University of Foggia (Foggia, Italy), from July 2023 to January 2025. All semen samples were analyzed using the LensHooke® X12 system, with additional aliquots assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test. Inter-test agreement between SCD-X12 and TUNEL was good in healthy men (accuracy: 77.0%) but poor in varicocele patients (accuracy: 61.0%), indicating that global SDF assays perform reliably under normal conditions but lose interpretability when DNA damage becomes heterogeneous, as seen in varicocele patients. Although DSBs theoretically contribute to global DNA fragmentation, agreement between DSB levels (SDFR-X12) and global SDF was modest in healthy subjects (prevalence-adjusted bias-adjusted kappa [PABAK]: 0.4) and negligible in varicocele patients (PABAK: 0.06), indicating that DSB-related damage is distinct and varicocele-specific. In conclusion, global SDF assays (TUNEL and SCD-X12) are informative in non-varicocele men. In contrast, the SDFR-X12 module identifies elevated DSBs as a varicocele-specific signature, offering clearer characterization of varicocele-associated DNA damage. By integrating semen parameters, global SDF, and DSB assessment, the automated X12 system enhances scenario-specific testing and supports improved management of varicocele-related male infertility.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148537949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ivan Ching-Ho Ko, Kevin Cheuk Kin Cheng, Chris Ho-Ming Wong, Joycelyn Yung Yung Lim, Candice Hiu Tung Mok, Cheuk Yi Tang, Brian Chun Fai Kwok, Yi-Hong Zhou, Chi Ho Leung, Peggy Sau Kwan Chu, Joseph Kai Man Li, Chi Fai Ng
{"title":"Disease characteries, treatment patterns, and oncological outcomes of de novo metastatic hormone-sensitive prostate cancer: real-world experience from a multicenter Asian cohort.","authors":"Ivan Ching-Ho Ko, Kevin Cheuk Kin Cheng, Chris Ho-Ming Wong, Joycelyn Yung Yung Lim, Candice Hiu Tung Mok, Cheuk Yi Tang, Brian Chun Fai Kwok, Yi-Hong Zhou, Chi Ho Leung, Peggy Sau Kwan Chu, Joseph Kai Man Li, Chi Fai Ng","doi":"10.4103/aja202616","DOIUrl":"10.4103/aja202616","url":null,"abstract":"<p><p>This multicenter retrospective study assessed real-world treatment patterns and outcomes in de novo metastatic hormone-sensitive prostate cancer (mHSPC) across five urological centers in Hong Kong (China; from 2016 to 2023). Of 3308 patients, 814 (24.6%) presented with de novo mHSPC. High-volume and high-risk disease were present in 59.1% and 53.8% of patients, respectively. Despite guidelines favoring intensified therapy, androgen deprivation therapy (ADT) monotherapy remained the most common treatment (52.0%), while only 28.7% received upfront chemotherapy (20.5%) or androgen receptor pathway inhibitors (ARPI; 8.2%). During a median 40-month follow-up period, 48.4% of patients died and 60.1% progressed to castration-resistant prostate cancer (CRPC) within a median of 19 months. Five-year overall survival rates were highest for ARPI (64.9%), followed by chemotherapy (53.5%) and monotherapy (38.7%), with corresponding 5-year CRPC-free survival rates of 73.5%, 7.7%, and 15.0%, respectively. Upfront chemotherapy and ARPI demonstrated significant reductions in cancer-specific mortality compared to ADT monotherapy (chemotherapy hazard ratio [HR]: 0.58, 95% confidence interval [CI]: 0.41-0.82, P = 0.002; ARPI HR: 0.32, 95% CI: 0.17-0.62, P < 0.001). High-volume disease (HR: 2.14, 95% CI: 1.52-3.01, P < 0.001) and ISUP Grade 4 or 5 (HR: 5.70, 95% CI: 1.82-17.87, P = 0.003) conferred increased risk. Upfront chemotherapy and ARPI were independently associated with improved overall survival (chemotherapy HR: 0.56, 95% CI: 0.41-0.78, P < 0.001; ARPI HR: 0.41, 95% CI: 0.24-0.69, P < 0.001). High-volume mHSPC (HR: 1.65, 95% CI: 1.24-2.21, P < 0.001) and ISUP Grade 4 or 5 (HR: 2.38, 95% CI: 1.22-4.65, P = 0.011) were significant adverse prognostic factors. Advanced age at diagnosis was associated with increased all-cause mortality (HR: 1.02, 95% CI: 1.00-1.03, P = 0.037). These findings highlight an urgent need to improve adoption of intensified treatment strategies for optimal patient outcomes.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148450959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Associations between serum total testosterone concentration and clinical pregnancy following IVF-ET in patients with azoospermia: a retrospective study.","authors":"Zhan Hu, Bo-Ya Zhao, Sen-Lin Shi, Qiong-Yao Shi","doi":"10.4103/aja202617","DOIUrl":"https://doi.org/10.4103/aja202617","url":null,"abstract":"<p><p>Serum total testosterone (TT) concentration is critical for male reproductive function, but its role in predicting in vitro fertilization-embryo transfer (IVF-ET) outcomes in patients with azoospermia remains unclear. In this retrospective study, the association between TT concentrations and clinical pregnancy outcomes was investigated in 2101 patients with azoospermia (1846 with obstructive azoospermia [OA] and 255 with nonobstructive azoospermia [NOA]) at The First Affiliated Hospital of Zhengzhou University (Zhengzhou, China), from January 2010 to January 2023. General characteristics of the patients in the pregnancy and nonpregnancy groups were compared. Logistic regression analysis was used to identify factors that affect pregnancy outcomes. A receiver operating characteristic curve (ROC) was plotted to determine the cut-off value of the TT concentration. Embryonic and clinical outcomes were compared using the TT cut-off value. The results revealed a significant negative correlation between the TT concentration and body mass index (BMI) in both cohorts. In patients with OA, female age (odds ratio [OR] = 0.96, 95% confidence interval [CI]: 0.92-0.99; P = 0.024) and the male TT concentration (OR = 1.14, 95% CI: 1.04-1.24; P = 0.005) were independent pregnancy predictors. We identified the TT concentration of 268 ng dl-1 as the favorable cut-off value. OA patients with TT levels of <268 ng dl-1 exhibited poorer sperm quality, reduced blastocyst formation, and diminished reproductive outcomes (all P < 0.05). We conclude that the TT concentration is correlated with BMI in patients with azoospermia and serves as an independent predictor of clinical pregnancy outcomes in patients with OA, but not in those with NOA. This provides a valuable clinical reference for subtype-specific management. However, its modest predictive performance limits its standalone clinical use.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katarzyna Warchoł-Biedermann, Ewa Mojs, Michał Ziarko
{"title":"Predictors and modulators of fertility quality of life in males undergoing their first fertility workup: a four time-point panel study.","authors":"Katarzyna Warchoł-Biedermann, Ewa Mojs, Michał Ziarko","doi":"10.4103/aja2025112","DOIUrl":"https://doi.org/10.4103/aja2025112","url":null,"abstract":"<p><p>This panel study explored predictors and modulators of fertility quality of life in involuntarily childless males undergoing fertility workup in an andrological outpatient clinic in Poznan, Poland. A convenience sample of 185 males, who were of 22-50 (mean ± standard deviation [s.d.]: 30.4 ± 4.4) years completed the core scale of Boivin's Fertility Quality of Life (FertiQoL) questionnaire (1) at the baseline, before their initial fertility evaluation (T1); (2) before their second andrological appointment, 2-3 months after the diagnostic disclosure (T2); and (3) before the third (T3) and the fourth (T4) treatment-related or checkup testing appointments. The timing of assessment was synchronized with respondent's andrological visits and routine medical procedures. The Kruskal-Wallis H test and Mann-Whitney U test with the Bonferroni adjustment were used to assess the association between core domain of FertiQoL and factors, such as age, educational status, financial status, marital duration, and female partner's need for fertility treatment. The study found FertiQoL outcomes in the sample were associated with a constellation of factors, whose importance might vary depending on the stage of the procedure. FertiQoL was both determined and modulated by both demographic and fertility-related factors. These characteristics included patient age, their female partner's age, and the interval between female's and male's initial fertility workup. The results of the current study have practical implications and should be considered in support programs for individuals and/or couples with unintentional childlessness.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shan-Shan Fan, Yi-Min Chen, Wen-Da Chen, Zheng-Hua Sun, Jian Yin, Mei Xie, Pu Wu
{"title":"Multidimensional explanations and future perspectives on the limited efficacy of immunotherapy in prostate cancer.","authors":"Shan-Shan Fan, Yi-Min Chen, Wen-Da Chen, Zheng-Hua Sun, Jian Yin, Mei Xie, Pu Wu","doi":"10.4103/aja202591","DOIUrl":"10.4103/aja202591","url":null,"abstract":"<p><p>As immunotherapy continues to push the envelope, it has had transformative success in malignancies such as melanoma and lung cancer. However, in contrast to these cancers, implementing immunotherapy in prostate cancer (PCa) still presents considerable difficulties. PCa itself is not sensitive to immunotherapy. The low response rate of PCa to immunotherapy cannot be attributed to a single mechanism. Instead, it results from the interplay of multiple adverse factors. These include the tumor's inherently low immunogenicity and the highly immunosuppressive properties of its tumor microenvironment. Taken together, these features create a \"perfect storm\" that severely limits the efficacy of immunotherapy. In this review, we comprehensively assess the latest advances in PCa immunotherapy, encompassing cancer vaccines, immune checkpoint inhibitors (ICIs), chimeric antigen receptor T cell (CAR-T) therapy, and various combination regimens. We also summarize their limited efficacy observed in clinical practice to date. Furthermore, we explore the underlying mechanisms contributing to the limited effectiveness of immunotherapy in PCa, with a focus on intrinsic molecular features, the immunosuppressive microenvironment, and key signaling pathways. Through an in-depth review of previous studies, we aim to provide a theoretical foundation and strategic guidance to enhance the effectiveness of immunotherapy for PCa and to facilitate the development and translation of more targeted and effective immunotherapeutic interventions.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":"345-358"},"PeriodicalIF":2.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13423391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146151366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jie Yang, Ya-Nan Gu, Qi Chen, Yu Xue, Man Yu, Sen Qiao, Sheng-Jia Shi
{"title":"Novel homozygous or compound heterozygous DNAH17 variants lead to male infertility characterized by multiple morphological abnormalities of the sperm flagella and asthenoteratozoospermia in humans.","authors":"Jie Yang, Ya-Nan Gu, Qi Chen, Yu Xue, Man Yu, Sen Qiao, Sheng-Jia Shi","doi":"10.4103/aja202567","DOIUrl":"10.4103/aja202567","url":null,"abstract":"<p><p>Genetic variants in the dynein axonemal heavy chain 17 ( DNAH17 ) have been implicated in multiple morphological abnormalities of the sperm flagella (MMAF) and asthenoteratozoospermia (ATZS). The aim of this study is to identify novel DNAH17 variants associated with MMAF and ATZS and to evaluate the impact of these variants on sperm motility, sperm morphology, the ultrastructure of sperm flagella, and the outcomes of intracytoplasmic sperm injection (ICSI). In the present study, we identified one novel homozygous and three compound heterozygous DNAH17 variants in one consanguineous and three nonconsanguineous families. Semen analysis revealed significant reductions in sperm motility and notable morphological changes. Transmission electron microscopy (TEM) revealed the absence of outer dynein arms (ODAs), loss of peripheral doublet microtubules (DMTs) 4-7, and multiple mitochondrial sheath (MS) abnormalities in the sperm flagella. Functional analyses indicated that these variants disrupted the expression and localization of the DNAH17 protein in the sperm flagella. Tandem mass tagging proteomics and immunofluorescence demonstrated a significant reduction in the expression of proteins associated with the assembly of ODA-associated proteins into the axoneme from individuals with DNAH17 variants. Notably, successful pregnancies were achieved through ICSI combined with assisted oocyte activation (AOA) treatment in the female partner of these probands. This study identified seven novel homozygous or compound heterozygous DNAH17 variants in both consanguineous and nonconsanguineous families, highlighting their detrimental effects on sperm motility, morphology, and flagellar ultrastructure. These findings provide valuable insights for the genetic diagnosis of MMAF and may enhance future genetic counseling strategies.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":"427-436"},"PeriodicalIF":2.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13423380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146000151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wen-Cong Jin, Dong Zhang, Ying-Hong Cui, Li Du, Zuping He
{"title":"NLRP3 activation by lipopolysaccharide (LPS) mediates the pyroptosis of human spermatogonial stem cells via GBP4 regulation.","authors":"Wen-Cong Jin, Dong Zhang, Ying-Hong Cui, Li Du, Zuping He","doi":"10.4103/aja202564","DOIUrl":"10.4103/aja202564","url":null,"abstract":"<p><p>Human spermatogonial stem cells (SSCs) are crucial for spermatogenesis and male reproduction. Although abnormal pyroptosis caused by inflammation impacts male fertility, the molecular mechanisms underlying the pyroptosis of human SSCs are elusive. To induce pyroptosis, lipopolysaccharide (LPS) was introduced into the vas deferens of mice. RNA sequencing (RNA-Seq) of human SSCs was employed to identify NOD-like receptor thermal protein domain associated protein 3 (NLRP3), and RNA interference (RNAi) was used to determine the function and mechanism of NLRP3 in controlling pyroptosis of human SSCs. Guanylate-binding protein 4 (GBP4) was analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction (PPI) analyses, and the impact of GBP4 on NLRP3 in human SSCs was subsequently assessed using GBP4 short hairpin RNA (shRNA). LPS reduced the testicular weight of mice, disrupted spermatogenesis, and increased the levels of inflammatory factors (interleukin-18 [IL-18] and interleukin-1β [IL-1β]). NLRP3 siRNAs antagonized the LPS-induced increases in IL-18 and IL-1β, proliferative inhibition, and pyroptosis (Caspase 1 and Gasdermin D) in human SSCs. An association between GBP4 and NLRP3 in human SSCs was identified by co-immunoprecipitation (Co-IP). Human SSCs with stable GBP4 shRNA decreased the expression level of NLRP3 in human SSCs under inflammatory conditions. Collectively, these results imply that LPS-induced NLRP3 activation enhances the pyroptosis of human SSCs via the regulation of GBP4. This study offers novel insights into molecular mechanisms underlying the fate determinations of human SSCs.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":"416-426"},"PeriodicalIF":2.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13423383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146000165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Small RNA profile alterations as a potential mechanism for sperm quality improvement following varicocelectomy.","authors":"Jian-Hui Li, Jian-Ying Li, Jia-Nan Tang, Xue-Mei Wang, Gao-Yue Zhang, Hao-Guang Huang, Xin Wang, Guo-Wu Chen, Guo-Qing Liang, Jian-Lin Hu, Tian-Cheng Zhang, Xu Zhang, Hui-Juan Shi, Min-Min Hua, Jin Zhang","doi":"10.4103/aja202568","DOIUrl":"10.4103/aja202568","url":null,"abstract":"<p><p>Varicocele-induced decline in sperm quality is a common cause of male infertility. While varicocelectomy improves semen parameters, the mechanisms remain unclear. Recent studies suggested that small noncoding RNAs (sncRNAs) in sperm play a significant role in male reproductive health. This study investigated whether varicoceles and surgical treatment influence the expression profiles of sperm sncRNAs and explored the related epigenetic mechanisms. This study included 63 infertile males undergoing varicocelectomy. Semen analysis was performed, followed by high-throughput deep sequencing of sperm sncRNAs both before and after surgery. The results indicated that semen parameters improved significantly following varicocelectomy. The expression profiles of sncRNAs were altered, with 10 microRNAs (miRNAs; 3 upregulated: hsa-miR-486-3p, hsa-miR-486-5p, and hsa-miR-874-3p; and 7 downregulated: hsa-miR-132-3p, hsa-miR-202-3p, hsa-miR-34c-5p, hsa-miR-499a-5p, hsa-miR-499b-3p, hsa-miR-520a-3p, and hsa-miR-92b-3p) showing significant changes post-surgery, which correlated with the improvement in sperm quality. Microinjection experiments demonstrated that the abnormally elevated expression of miRNAs in zygotes (miR-132-3p, miR-34c-5p, and miR-520a-3p) may negatively affect early embryonic development. Together, these results suggest that abnormal miRNA expression is a potential epigenetic mechanism underlying varicocele-associated sperm quality impairment. Moreover, the study findings provide evidence that varicocelectomy can relieve this process. Furthermore, the differentially expressed miRNAs may serve as potential predictors for diagnosing different pathological types of infertility and represent new molecular targets for improving fertility in males with varicoceles.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":"437-446"},"PeriodicalIF":2.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13423388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146000095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aljazi Abdullah AlRashidi, Sahar Y Rajeh, Khaled Hamden
{"title":"C-phycocyanin protects against obesity-associated type 2 diabetes-induced male fertility dysfunction via key enzyme regulation.","authors":"Aljazi Abdullah AlRashidi, Sahar Y Rajeh, Khaled Hamden","doi":"10.4103/aja2025108","DOIUrl":"10.4103/aja2025108","url":null,"abstract":"<p><p>The prevalence of male infertility is steadily increasing and has become a growing global health concern. The goal of this study is to evaluate the therapeutic potential of C-phycocyanin (CPC), a natural phycobiliprotein pigment extracted from Spirulina platensis (Sp), on male reproductive dysfunction in obese rats with type 2 diabetes (OB-T2D). Daily treatment was administered for 3 months. CPC at 300 mg kg -1 significantly reduced body weight (-35.6%) and blood glucose levels (-40.2%). It markedly suppressed seminal plasma inflammation by reducing leukocyte count and the activities of myeloperoxidase (MPO), phospholipase A2 (PLA2), and elastase (ELA) in seminal plasma by 77.3%, 63.1%, and 55.4%, respectively. CPC significantly improved sperm quality by increasing sperm concentration as well as the percentages of sperm viability and motility, while significantly reducing the percentage of sperm abnormalities. In parallel, CPC stimulated key fertility-related enzymes, including 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD), adenosine triphosphatase (ATPase), prostatic acid phosphatase (PAP), lactate dehydrogenase (LDH), and adenosine deaminase (ADA), while downregulating phosphodiesterase (PDE). Moreover, CPC optimized seminal plasma composition by increasing fructose levels, modulating pH, and enhancing the activity of hyaluronidase (HYAL) and alkaline phosphatase (ALP). Seminal plasma antioxidant defense was strengthened via increased activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione S-transferase (GST); and reduced oxidative stress markers including total oxidant status (TOS), hydrogen peroxide (H 2 O 2 ), and thiobarbituric acid reactive substances (TBARS). Therefore, CPC exerts a potent protective effect against OB-T2D-induced reproductive dysfunction by improving sperm parameters, enzymatic activity, and seminal antioxidant capacity.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":"398-408"},"PeriodicalIF":2.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13423384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147286571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}