{"title":"Expression of miR-339-3p and OPRM1 in relation to sperm function in male infertility.","authors":"Ashraf Elsaid, Ahmed Fathy State, Adel Zalata, Randa El-Gamal, Moheiddin Alghobary","doi":"10.1111/andr.70121","DOIUrl":"https://doi.org/10.1111/andr.70121","url":null,"abstract":"<p><strong>Background: </strong>Infertility is the inability of a couple to conceive after 12 months of unprotected intercourse. The µ-opioid receptor involved in mediating opioid effects and may be associated with male fertility. µ-Opioid receptors were expressed in testicular tissues and spermatozoa, where they may influence spermatogenesis and sperm motility. miR-339-3p was thought to suppress OPRM1 mRNA expression in neuronal cells following opioid exposure through post-transcriptional modulation. However, its role in male infertility remains unexplored.</p><p><strong>Objectives: </strong>To investigate the relationship between miR-339-3p expression, OPRM1 mRNA expression, and µ-opioid receptor protein level in spermatozoa of infertile versus fertile men, and to assess their association with semen parameters, oxidative stress, and hormonal profile.</p><p><strong>Materials and methods: </strong>This case-controlled study was conducted on 45 infertile men and 45 healthy fertile men recruited from andrology outpatient clinic, Mansoura University Hospital. Semen analysis, acrosin activity, oxidative stress markers, and serum hormones levels were evaluated. Relative quantification of miR-339-3p and OPRM1 mRNA expression was quantified using qRT-PCR. µ-Opioid receptor protein levels were measured by enzyme-linked immunosorbent assay technique. Correlation and receiver-operating characteristic analyses were performed.</p><p><strong>Results: </strong>Infertile men exhibited significantly elevated levels of µ-opioid receptor protein (median: 6.41 ng/mL) compared to fertile controls (5.45 ng/mL, p < 0.001), alongside a marked upregulation of OPRM1 mRNA expression (relative quantification = 4.05 vs. 0.993, p < 0.001), representing approximately a 4.08-fold increase. In contrast, miR-339-3p expression was significantly reduced in the infertile group (relative quantification = 0.538 vs. 1.01, p < 0.001), indicating an approximate 0.53-fold change, or nearly 2-fold downregulation. A significant negative correlation was observed between miR-339-3p and OPRM1 mRNA levels (r<sub>s</sub> = -0.704, p < 0.001). Receiver-operating characteristic analysis indicated excellent diagnostic accuracy for OPRM1 mRNA (AUC = 0.916) and miR-339-3p (AUC = 0.914) in differentiating infertile from fertile men.</p><p><strong>Conclusions: </strong>Downregulation of miR-339-3p and overexpression of µ-opioid receptor are associated with impaired semen quality and oxidative imbalance in infertile men. These molecular markers may serve as potential diagnostic indicators in male infertility, pending further validation.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of neonatal hypothyroidism on testicular development and undifferentiated spermatogonia in prepubertal rats.","authors":"Daisuke Matsumoto, Kentaro Mizuno, Hidenori Nishio, Hideyuki Kamisawa, Takuya Sakata, Taiki Kato, Akihiro Nakane, Satoshi Kurokawa, Tetsuji Maruyama, Yutaro Hayashi, Takahiro Yasui","doi":"10.1111/andr.70116","DOIUrl":"https://doi.org/10.1111/andr.70116","url":null,"abstract":"<p><strong>Background: </strong>Thyroid hormones play a key role in testicular development, particularly in the regulation of Sertoli cell proliferation and differentiation. While congenital hypothyroidism is common and treatable, the effects of thyroid hormone insufficiency on early testicular development during the neonatal period remain unclear.</p><p><strong>Objectives: </strong>This study investigated the effects of transient and continuous hypothyroidism during the neonatal and prepubertal periods on testicular development, focusing on spermatogonial stem cell dynamics through histological and germ cell marker analyses.</p><p><strong>Materials and methods: </strong>We established two neonatal rat models using 6-n-propyl-2-thiouracil: a continuous hypothyroidism model and a transient neonatal hypothyroidism model. 6-n-Propyl-2-thiouracil was administered to lactating dams at concentrations of 0.001%, 0.01%, and 0.03%. Male offspring were evaluated on postnatal days 7, 10, and 20 for serum hormone levels, body and testicular growth, and immunohistochemical markers (GFRA1, DDX4, SOX9, and Ki-67).</p><p><strong>Results: </strong>The transient hypothyroidism model successfully induced transient hypothyroidism without systemic growth impairment. Serum thyroxine and thyroid-stimulating hormone levels were normalized by day 20. GFRA1-positive undifferentiated germ cells consistently increased in all 6-n-propyl-2-thiouracil groups on days 7 and 20. Co-expression with Ki-67 indicated cell proliferation. The formation of seminiferous tubule lumen was reduced in a dose-dependent manner.</p><p><strong>Discussion: </strong>Transient neonatal hypothyroidism increases the number of undifferentiated germ cells, potentially including spermatogonial stem cells. The transient hypothyroidism model minimizes systemic effects and allows the observation of testis-specific responses to thyroid disruption.</p><p><strong>Conclusion: </strong>This study demonstrated that even low-dose transient hypothyroidism during the neonatal period enhances the population of undifferentiated germ cells, potentially including spermatogonial stem cells. The transient hypothyroidism model offers a physiologically relevant and minimally invasive platform to explore how early thyroid hormone imbalances influence germ cell population establishment during a critical window of testicular development, potentially reflecting the clinical scenarios of treated congenital hypothyroidism.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AndrologyPub Date : 2025-09-12DOI: 10.1111/andr.70119
Wenxin Ma, Chang Liu, Jing Pu, Ziyu Liu, Na Hu, Li Yang, Dongmei Chen, Hongmei Li, HuiMing Ma
{"title":"Lycium barbarum polysaccharides enhance testicular spermatogenesis in d-galactose-induced aging rats via calcium signaling.","authors":"Wenxin Ma, Chang Liu, Jing Pu, Ziyu Liu, Na Hu, Li Yang, Dongmei Chen, Hongmei Li, HuiMing Ma","doi":"10.1111/andr.70119","DOIUrl":"https://doi.org/10.1111/andr.70119","url":null,"abstract":"<p><strong>Background: </strong>Lycium barbarum polysaccharide (LBP) has long been recognized as having a wide range of beneficial properties for improving proliferation. However, the protective effects and specific mechanisms of d-galactose-induced testicular dysfunction in reproductively senescent rats are not fully understood.</p><p><strong>Materials and methods: </strong>A d-galactose-induced senescence model in male rats and a d-galactose-induced TM3 cell model were used to investigate the effects of LBP. The protective effect on testicular spermatogenic function was assessed by histological analysis and SA-β-gal staining. In addition, key calcium signaling pathway alterations involved in LBP were assessed using a multi-omics approach and validated by tissue. Single-cell sequencing data were used to further analyze the cellular heterogeneity of calcium signaling.</p><p><strong>Results: </strong>LBP significantly improved testicular structure, increased the number of spermatogonia in the seminiferous tubules, and significantly attenuated oxidative stress and testicular apoptosis. In addition, LBP restored the expression of key steroidogenic enzymes, as well as elevated levels of testosterone, follicle-stimulating hormone (FSH), and estradiol (E2), and decreased levels of luteinizing hormone (LH). Mechanistically, LBP regulates key signaling pathways, including calcium homeostasis, Hippo and mTOR pathways, which play important roles in cell growth, apoptosis, and tissue regeneration. Single-cell sequencing data show that calcium signaling is more active in the elderly compared to the young, mainly in Leydig cells, Round Spermatids, and Smooth Muscle Cells. In TM3 cell experiments, the LBP reduced SA-β-gal activity, downregulated aging markers (p16, p21, p53), and restored steroid production function. In addition, LBP regulated the Ca<sup>2</sup>⁺/CaM/CaMKII signaling pathway, improved calcium homeostasis, and reduced apoptosis in rats and cells.</p><p><strong>Conclusion: </strong>LBP improves d-galactose-induced testicular spermatogenesis mainly by regulating calcium signaling and metabolic pathways and is closely related to elongating spermatids, round spermatids.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Real-world pharmacovigilance assessment of drug-induced male hypogonadism risks: An analysis of FDA adverse drug event data.","authors":"Yujia Xi, Yijun Jia, Zhanlong Zheng, Xinfang Cao, Zhinan Jing, Jingqi Wang","doi":"10.1111/andr.70120","DOIUrl":"https://doi.org/10.1111/andr.70120","url":null,"abstract":"<p><strong>Background: </strong>Drug-induced hypogonadism is an underrecognized but significant adverse effect of various medications, contributing to male sexual dysfunction and infertility. Despite its clinical significance, comprehensive studies systematically identifying high-risk drugs remain limited.</p><p><strong>Objectives: </strong>This study aimed to investigate the potential drugs associated with hypogonadism from FDA Adverse Event Reporting System.</p><p><strong>Materials and methods: </strong>This study analyzed adverse drug events reported from FDA Adverse Event Reporting System covering the period from the first quarter of 2004 to the third quarter of 2024. Cases related to hypogonadism were identified using standardized Medical Dictionary for Regulatory Activities preferred terms. Disproportionality analyses were conducted using the reporting odds ratio and the Bayesian confidence propagation neural network. Drugs were classified according to Anatomical Therapeutic Chemical classification system and clinical applications. This study utilized FDA Label to determine whether adverse drug events related to male hypogonadism are mentioned on their labels.</p><p><strong>Results: </strong>We identified 10 classes including 42 drugs that showed positive signals for both reporting odds ratio and Bayesian confidence propagation neural network: anesthetics and analgesics, psychiatric and neurological medications, antineoplastic agents, urological medications, hormonal agents, cardiovascular medications, gastrointestinal medications, bone metabolism modifiers, antiretroviral agents, and other drugs. According to the Bayesian confidence propagation neural network algorithm, 6 drugs were considered to have a high risk of causing hypogonadism, and 11 drugs had medium risk. In addition, 20 drugs did not mention adverse drug events related to male hypogonadism, of which 3 were identified as high risk using the Bayesian confidence propagation neural network algorithm.</p><p><strong>Conclusions: </strong>This research summarized a list of potential drugs associated with hypogonadism. A clear understanding of the risk and frequency of drug-induced hypogonadism can reduce the likelihood of patients developing the condition.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145022648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AndrologyPub Date : 2025-09-08DOI: 10.1111/andr.70105
{"title":"Joint Congress of the American Society of Andrology & International Congress of Andrology 2025","authors":"","doi":"10.1111/andr.70105","DOIUrl":"https://doi.org/10.1111/andr.70105","url":null,"abstract":"","PeriodicalId":7898,"journal":{"name":"Andrology","volume":"13 S1","pages":"1-148"},"PeriodicalIF":3.4,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Machine learning-based personalized prediction of sperm retrieval in patients with non-obstructive azoospermia prior to microdissection testicular sperm extraction: A multi-center cohort study.","authors":"Yu Xi, Bailing Zhang, Yun Zhang, Lianming Zhao, Defeng Liu, Jiaming Mao, Wenhao Tang, Haitao Zhang, Haocheng Lin, Xiaoyan Wang, Pengcheng Ren, Yanlin Tang, Yuzhuo Yang, Kai Hong, Jingtao Guo, Zhe Zhang, Hui Jiang","doi":"10.1111/andr.70114","DOIUrl":"https://doi.org/10.1111/andr.70114","url":null,"abstract":"<p><strong>Background: </strong>Non-obstructive azoospermia represents the most severe form of male infertility. The heterogeneous nature of focal spermatogenesis within the testes of non-obstructive azoospermia patients poses significant challenges for accurately predicting sperm retrieval rates.</p><p><strong>Objectives: </strong>To develop a machine learning-based predictive model for estimating sperm retrieval rates in patients with non-obstructive azoospermia.</p><p><strong>Materials and methods: </strong>This multi-center study included more than 2800 men with non-obstructive azoospermia who underwent microdissection testicular sperm extraction. Preoperative clinical variables were used to train, test, and validate multiple machine learning models. The predictive performance of eight models was assessed with several metrics, including area under the receiver operating characteristic curve, overall accuracy, etc. RESULTS: Of the eight models evaluated, Extreme Gradient Boosting, Random Forest, and Light Gradient Boosting Machine consistently outperformed the others. Extreme Gradient Boosting, which achieved the highest mean area under the receiver operating characteristic curve (0.9183), was selected to power SpermFinder-an online calculator for sperm retrieval rates prediction. The model maintained strong discriminatory ability in both validation sets, with an area under the receiver operating characteristic curve of 0.8469 in the internal cohort and 0.8301 in the external cohort.</p><p><strong>Discussion and conclusion: </strong>By leveraging routine clinical features and machine learning-powered models, we developed a web-based platform that reliably predicts sperm retrieval outcomes in men with non-obstructive azoospermia. The predictive tool could provide valuable insights for preoperative assessments, and patients with a lower probability of success could gain the opportunity to make informed decisions.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AndrologyPub Date : 2025-09-05DOI: 10.1111/andr.70117
Weerayut Wiriyabanditkul, Guiting Lin, Majken Højrup Wiborg, Xianghu Meng, Caipeng Qin, Lia Banie, Guifang Wang, Tom F Lue
{"title":"Amniotic fluid stem cell therapy improves erectile function in a diabetic rat model.","authors":"Weerayut Wiriyabanditkul, Guiting Lin, Majken Højrup Wiborg, Xianghu Meng, Caipeng Qin, Lia Banie, Guifang Wang, Tom F Lue","doi":"10.1111/andr.70117","DOIUrl":"https://doi.org/10.1111/andr.70117","url":null,"abstract":"<p><strong>Background: </strong>Current treatments for diabetic erectile dysfunction, such as phosphodiesterase type 5 inhibitors, penile injection, or vacuum erection devices, primarily offer symptomatic relief and do not address the underlying pathophysiology, which involves neural, vascular, and smooth muscle degeneration.</p><p><strong>Objectives: </strong>This study aimed to evaluate the therapeutic potential of amniotic fluid-derived stem cells in a rat model of diabetic erectile dysfunction by assessing their impact on erectile function and penile tissue regeneration.</p><p><strong>Methods: </strong>Male Sprague‒Dawley rats were divided into control, diabetic, and amniotic fluid-derived stem cell-treated diabetic groups. Diabetes was induced using streptozotocin (60 mg/kg). Five weeks after intracavernous injection of amniotic fluid-derived stem cells (1 × 10<sup>6</sup> cells per rat), erectile function, penile nerves, endothelial cells, and smooth muscle cells were evaluated through intracavernous pressure measurements, histological analyses, and cellular senescence assessments using class III β-tubulin (TUBB3), rat endothelial cell antigen, and α-smooth muscle actin markers, respectively, along with β-galactosidase staining.</p><p><strong>Results: </strong>Amniotic fluid-derived stem cell treatment significantly improved erectile function in diabetic rats, as evidenced by increased intracavernous pressure/mean arterial pressure ratios than untreated diabetic rats (p = 0.0307). Immunofluorescence revealed restoration of neuronal and endothelial markers, while α-smooth muscle actin expression increased and β-galactosidase activity decreased, indicating enhanced smooth muscle integrity and reduced cellular senescence.</p><p><strong>Conclusion: </strong>Intracavernous amniotic fluid-derived stem cell therapy effectively restores erectile function and mitigates tissue damage in diabetic rats by promoting neurovascular regeneration and reducing senescence, highlighting amniotic fluid-derived stem cells as a promising regenerative therapy for diabetic erectile dysfunction and supporting further pre-clinical and clinical investigations.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144999442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AndrologyPub Date : 2025-08-29DOI: 10.1111/andr.70111
Giorgio Ivan Russo, Edoardo Pozzi, Fausto Negri, Marco Falcone, Emanuele Zupo, Mirko Preto, Maria Giovanna Asmundo, Sandrine Chamayou, Murat Dursun, Ateş Kadıoğlu, Andrea Salonia
{"title":"Development of a nomogram for sperm retrieval at microTESE for idiopathic non-obstructive azoospermia in a multi-center cohort study.","authors":"Giorgio Ivan Russo, Edoardo Pozzi, Fausto Negri, Marco Falcone, Emanuele Zupo, Mirko Preto, Maria Giovanna Asmundo, Sandrine Chamayou, Murat Dursun, Ateş Kadıoğlu, Andrea Salonia","doi":"10.1111/andr.70111","DOIUrl":"https://doi.org/10.1111/andr.70111","url":null,"abstract":"<p><strong>Background: </strong>Non-obstructive azoospermia (NOA) affects approximately 10% of infertile men and represents a major challenge in assisted reproductive technology (ART). A model that includes histological variants could be helpful in predicting sperm retrieval rate (SRR) after microdissection testicular sperm extraction (mTESE) in patients affected by NOA and without genetic abnormalities OBJECTIVES: To develop and validate a predictive nomogram integrating clinical and histopathological variables to estimate SRR in NOA patients undergoing microTESE.</p><p><strong>Material and methods: </strong>A multi-center retrospective/prospective cohort study was conducted between 2022 and 2024, enrolling 333 men diagnosed with NOA across six academic centers. Preoperative data, including age, body mass index (BMI), hormonal profile (follicle-stimulating hormone [FSH], luteinizing hormone [LH], testosterone), genetic analysis, and ultrasound-measured testicular volume, were collected. MicroTESE was performed under microscopic guidance with histopathological evaluation. Predictive factors for successful sperm retrieval were analyzed through logistic regression, and a predictive nomogram was constructed and internally validated using bootstrapping techniques. Multi-variate logistic regression was performed to identify independent variables associated with SRR in patients with available final pathology. Therefore, a predictive nomogram was developed and validated using 1000 bootstrap samples.</p><p><strong>Results: </strong>The overall SRR was 52.55%. Multi-variate analysis identified FSH levels (odds ratio [OR]: 0.97; p = 0.049), maturation arrest (OR: 0.04; p < 0.01), and Sertoli cell-only syndrome (SCOS; OR: 0.03; p < 0.01) as independent predictors of SRR. The predictive nomogram demonstrated good accuracy, with a C-index of 0.75, sensitivity of 73%, specificity of 82%, and overall accuracy of 77% at a cutoff of 0.33.</p><p><strong>Discussion: </strong>Using preoperative and histology data, we developed a nomogram to predict SR outcomes in patients with NOA undergoing mTESE. Our findings demonstrate that integrating hormonal and histopathological data enhances predictive accuracy of the model, thus providing a valuable tool for preoperative counseling and clinical decision-making in couples presenting with infertility.</p><p><strong>Conclusion: </strong>This validated nomogram effectively predicts sperm retrieval outcomes in NOA patients undergoing microTESE, facilitating improved patient counseling, informed clinical decisions, and optimized patient selection. Prospective external validation and further model refinement are recommended to enhance generalizability and clinical applicability.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparative analysis of reproductive toxicity of polystyrene-nanoplastics and polystyrene-microplastics in rat Sertoli cells.","authors":"Ying Hu, Shuyi Jiang, Ying Xu, Yuqi Zhang, Qiang Zhang, Wenjie Zhou, Jinhong Liang, Wenhui Su","doi":"10.1111/andr.70115","DOIUrl":"https://doi.org/10.1111/andr.70115","url":null,"abstract":"<p><strong>Background: </strong>Microplastic pollution increasingly affects human health. Polystyrene nanoparticles (PS-NPs) and microplastics (PS-MPs) may impair Sertoli cells (SCs), vital for male fertility.</p><p><strong>Objectives: </strong>To compare PS-NPs (80 nm)/PS-MPs (8 µm) toxicity on rat SCs, focusing on oxidative stress, apoptosis, epithelial barrier integrity, endocytosis pathways, and miRNA-mediated ceRNA networks.</p><p><strong>Materials/methods: </strong>SCs viability was assessed via CCK-8. Trans-epithelial electrical resistance (TER) was measured to assess the epithelial barrier function. Particle internalization was evaluated by confocal microscopy and flow cytometry. Endocytosis was detected by using specific inhibitors. Whole-transcriptome sequencing profiling identified differential expression of miRNAs, lncRNAs, circRNAs, and mRNAs, with subsequent ceRNA network construction. Pro-inflammatory factors and apoptosis were detected by RT-qPCR and flow cytometry, respectively.</p><p><strong>Results: </strong>At 100 µg/mL, PS-NPs reduced cell viability to 77% versus 94% for PS-MPs (p < 0.05) and decreased TER by 81% versus 63% for PS-MPs (p < 0.01). PS-NPs were internalized via clathrin- and caveolin-dependent pathways, while PS-MPs remained extracellular. RNA-seq revealed PS-MPs activated inflammation pathways (Ank3/Daxx), while PS-NPs triggered oxidative stress and apoptosis pathways (Map2k4/Grin2a). PS-NPs induced higher apoptosis (17% vs. 9.3%, p < 0.01), Reactive oxygen species (3.7-fold vs. 1.87-fold), and more severe catalase activity reduction (67% vs. 17%, p < 0.01) compared to PS-MPs.</p><p><strong>Discussion and conclusion: </strong>PS-NPs pose greater toxicity to SCs than PS-MPs due to cellular internalization, disrupting barrier integrity via oxidative stress/apoptosis. PS-MPs primarily trigger extracellular inflammation. Distinct ceRNA networks underpin their differential mechanisms. These results highlight risks of environmental microplastic fragmentation into nanoplastics, emphasizing the need for further research on microplastic impacts on male fertility.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
AndrologyPub Date : 2025-08-21DOI: 10.1111/andr.70109
Sandro C Esteves
{"title":"From classification to clinical impact: The APHRODITE criteria and hormonal therapy for idiopathic male infertility.","authors":"Sandro C Esteves","doi":"10.1111/andr.70109","DOIUrl":"https://doi.org/10.1111/andr.70109","url":null,"abstract":"","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}