Andrology最新文献

{"title":"Cardiac function and coronary plaque development following masculinizing gender-affirming hormone therapy: A prospective cohort study.","authors":"Laust Frisenberg Buhl, Marianne S Andersen, Jan Frystyk, Axel Diederichsen, Selma Hasific, Rikke Hjortebjerg, Jordi Sanchez Dahl, Manijeh Noori, Kirstine Nørregaard Hansen, Gitte Maria Jørgensen, Camilla Viola Palm, Tine Taulbjerg Kristensen, Dorte Glintborg, Louise Lehmann Christensen","doi":"10.1111/andr.13832","DOIUrl":"https://doi.org/10.1111/andr.13832","url":null,"abstract":"<p><strong>Introduction: </strong>Myocardial dysfunction and the presence of calcified and non-calcified coronary plaques are predictors of cardiovascular disease. Masculinizing gender-affirming hormone therapy may increase cardiovascular risk, highlighting the need for prospective studies to evaluate cardiovascular outcomes during gender-affirming hormone therapy.</p><p><strong>Objectives: </strong>To evaluate changes in cardiac morphology, systolic and diastolic function, and development of coronary plaques after masculinizing gender-affirming hormone therapy.</p><p><strong>Methods: </strong>Prospective study including 47 transmasculine persons (gender-affirming hormone therapy-naïve, TransM_TN, n = 15 and gender-affirming hormone therapy-ongoing, TransM_TO, n = 32). Included persons were evaluated at study inclusion and after one year of masculinizing gender-affirming hormone therapy. At baseline, the median age of TransM_TN was 22 years (interquartile range 19-28 years) and TransM_TO 26 years (interquartile range 24-37 years) with a median gender-affirming hormone therapy duration of 4 years (interquartile range 2-5 years). Cardiac morphology including left ventricular wall thickness, volume, and mass, as well as left ventricular systolic and diastolic function was evaluated using echocardiography. Coronary artery calcifications and non-calcified coronary plaque were assessed using coronary computed tomography angiography. Paired and unpaired statistical analyses were performed within and between TransM_TN and TransM_TO groups.</p><p><strong>Results: </strong>In TransM_TN, diastolic function decreased during follow-up with decreased septal and lateral left ventricular relaxation (14-11 cm/s, p = 0.04 and 18-15 cm/s, p = 0.02, respectively). No significant changes were observed in cardiac morphology, systolic function, or formation of coronary artery calcifications and non-calcified coronary plaque in TransM_TN or TransM_TO groups. At baseline, left ventricular end-diastolic internal diameter was significantly higher in TransM_TO compared to TransM_TN, 4.6 cm (interquartile range 4.3-5.0 cm) versus 4.4 cm (interquartile range 4.2-4.6 cm), p < 0.05. Other baseline cardiac outcomes were comparable between TransM_TN and TransM_TO.</p><p><strong>Conclusion: </strong>Diastolic function declined after the initiation of masculinizing gender-affirming hormone therapy and individuals on long-term masculinizing gender-affirming hormone therapy had larger left ventricular dimensions compared to individuals before gender-affirming hormone therapy initiation. Cardiac morphology, systolic function, and coronary plaque formation remained stable during masculinizing gender-affirming hormone therapy.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977105","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":"Short and long-term effects of experimental varicocele.","authors":"Aram Minas, Dunia Waked, Valter Luiz Maciel Júnior, Mika Alexia Miyazaki, Raquel Lozano Guilharducci, Mariana Pereira Antoniassi, Mariana Matera Veras, Ricardo Pimenta Bertolla","doi":"10.1111/andr.13841","DOIUrl":"https://doi.org/10.1111/andr.13841","url":null,"abstract":"<p><strong>Background: </strong>Varicocele is associated with a progressive decrease in male fertile potential, but it has yet to be determined if the duration of varicocele is associated with altered sperm functional quality.</p><p><strong>Objectives: </strong>This experimental study investigated the time-dependent effects of varicocele on spermatogenesis, sperm parameters, and sperm functional traits.</p><p><strong>Materials and methods: </strong>Thirty-five mature male Wistar rats (200 ± 25 g) were included. After 2 weeks of adaptation, rats were randomly divided (n = 7/group) into control, 2 months sham (sham-2), 2 months varicocele (VCL-2), 4 months sham (sham-4), and 4 months varicocele (VCL-4) groups. Cauda epididymides were incised transversally and incubated in Biggers-Whitten-Whittingham media at 37°C for 30 min. Sperm concentration, motility, morphology, viability, mitochondrial activity (3,3' diaminobenzidine staining), acrosome integrity (PNA-FITC), and DNA fragmentation (alkaline Comet assay) were determined. Histological analysis on testicular cross-sections was performed using H&E staining, and Johnsen's score was determined for each sample.</p><p><strong>Results: </strong>Decreased Johnsen score, sperm count, motility, viability, normal morphology, and mitochondrial activity were observed in VCL-2 and VCL-4 groups when compared with sham-2, sham-4, and control groups. Higher levels of acrosome damage and DNA fragmentation were observed in VCL-2 and VCL-4 groups compared to sham and control groups. A negative correlation was observed between Johnsen scores and acrosome damage (r = -0.7690; p < 0.0001), and a positive correlation was observed between Johnsen scores and sperm DNA fragmentation (r = 0.8333; p < 0.0001). No differences were observed between the VCL-2 and VCL-4 groups in any of the analyses.</p><p><strong>Discussion and conclusion: </strong>Experimental varicocele leads to decreased semen quality, sperm functional integrity, and Johnsen's scores. Moreover, to our knowledge, this is the first study demonstrating a direct association between spermatogenesis and sperm count, motility, acrosomal integrity, and DNA fragmentation levels in experimental varicocele. Longer periods of varicocele did not potentiate the negative effects, in this study.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977112","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":"Direct-to-consumer semen analysis products: Content, accountability, and adherence to clinical guidelines.","authors":"John Ernandez, Grayden Cook, Brittany Berk, Alexandra J Berger, Martin Kathrins","doi":"10.1111/andr.13840","DOIUrl":"https://doi.org/10.1111/andr.13840","url":null,"abstract":"<p><strong>Background: </strong>Direct-to-consumer (DTC) semen analysis (SA) products obviate barriers that deter men from clinic testing and have made strides in providing higher quality data. However, it is unclear how well these products adhere to the 2021 WHO guidelines on examination and processing of human spermatozoa as they pertain to the evaluation of male fertility.</p><p><strong>Objective: </strong>We investigate the content and adherence to clinical guidelines associated with consumer-facing information on DTC analysis products.</p><p><strong>Materials and methods: </strong>Google search terms \"at-home sperm test\" and \"mail-in sperm test\" were used to identify commercially available products. Products that were offered to providers or were designed for use after vasectomy were excluded. We determined which semen parameters each product offered; if it was validated in subfertile men and against an established semen analysis method; and if it provided guidance in accordance with the WHO 2021 guidelines and related AUA/ASRM guidelines. The accountability and esthetic appearance of content for each product were assessed using the Silberg accountability and modified Abbott's criteria, respectively. Readability was assessed using the Flesch-Kincaid score. Descriptive statistics and two-tailed t-tests were used to compare characteristics, with p < 0.05 as statistically significant.</p><p><strong>Results: </strong>We identified 20 at-home (n = 17) and mail-in (n = 3) products. 85% of tests reported sperm concentration, with 60% and 15% of tests reporting motility and morphology, respectively. Fewer than half recommended men perform more than one test (40%), and none highlighted the need for partner evaluation. Only 25% were validated among subfertile men. Most tests lacked information on their credentials and sponsors, though were esthetically pleasing. Consumer-facing information on average required a high school level education for comprehension.</p><p><strong>Conclusions: </strong>DTC products inconsistently provide clinical recommendations in accordance with guidelines. Additionally, while product content is on average aesthetically appealing, it may lack accountability. Formal recommendations on the content and use of such products may improve their clinical integration.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977110","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":"The effects of regular exercise on cognitive and cardiometabolic health in testicular cancer survivors subjected to platinum-based chemotherapy.","authors":"Ali Amiri, Lucia Slobodová, Radka Klepochová, Martin Schön, Karin Marček Malenovská, Katarína Rerková, Radka Pechancová, Martin Prievalský, Viera Litváková, Viktor Oliva, Tomáš Pluháček, Milan Sedliak, Michal Mego, Martin Krššák, Michal Chovanec, Barbara Ukropcová, Jozef Ukropec","doi":"10.1111/andr.13829","DOIUrl":"https://doi.org/10.1111/andr.13829","url":null,"abstract":"<p><strong>Background: </strong>Platinum-based chemotherapy provides curative treatment to more than 95% of patients with testicular germ cell tumor but it has negative cardiometabolic and neurological effects. Regular exercise can alleviate late chemotherapy-related toxicities. We examined the impact of a 6-month supervised aerobic-strength training on cognitive and cardiometabolic health and residual level of platinum in cancer survivors.</p><p><strong>Methods: </strong>Twenty-eight middle-aged (42.1 ± 7.6 years) testicular germ cell tumor survivors subjected to platinum-based chemotherapy (1-8 cycles, 0-24 years ago) were recruited into exercise (n = 20) and control (n = 8) groups. Effects of 6-month exercise training on the whole-body and muscle metabolism, cognitive functions, cardiopulmonary fitness, residual plasma platinum, and plasma adiponectin were examined.</p><p><strong>Results: </strong>Exercise intervention improved cardiopulmonary fitness and cognitive functions, reduced residual plasma platinum, visceral adiposity and muscle lipids, improved glucose (glycosylated hemoglobin) and lipid (high-density lipoprotein cholesterol) metabolism, and enhanced dynamics of muscle post-exercise phosphocreatine recovery. Exercise-related decline in plasma platinum was paralleled by decline of muscle glycerophosphocholines and by the enhanced metabolic flexibility during low-intensity exercise, and predicted training-induced increase in cognitive functions.</p><p><strong>Conclusions: </strong>The 6-month exercise intervention resulted in improved cognitive and cardiometabolic health in testicular germ cell tumor survivors, which was paralleled by reduced plasma platinum, providing evidence that structured supervised exercise brings multiple health benefits to testicular germ cell tumor survivors.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942861","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":"A recurrent loss-of-function variant in DRC1 causes non-syndromic severe asthenozoospermia with favorable intracytoplasmic sperm injection and pregnancy outcomes.","authors":"Célia Tebbakh, Anne-Laure Barbotin, Guillaume Martinez, Angèle Boursier, Zeina Wehbe, Asma Hammouda, Nicolas Thierry-Mieg, Christophe Arnoult, Selima Fourati Ben Mustapha, Raoudha Zouari, Pierre F Ray, Zine-Eddine Kherraf","doi":"10.1111/andr.13837","DOIUrl":"https://doi.org/10.1111/andr.13837","url":null,"abstract":"<p><strong>Background: </strong>Asthenozoospermia, characterized by reduced sperm motility, is a common cause of male infertility. Multiple morphological abnormalities of the sperm flagella (MMAF) represent a severe and genetically heterogeneous form of asthenozoospermia. Over 50 genes have been associated, but approximately half of MMAF cases remain unexplained. DRC1, a gene involved in the nexin-dynein regulatory complex (N-DRC), has been linked to MMAF and primary ciliary dyskinesia (PCD), often with significant variability in clinical presentation.</p><p><strong>Objectives: </strong>His study aimed to identify novel pathogenic DRC1 variants in MMAF patients, assess their impact on sperm flagellar structure, and evaluate intracytoplasmic sperm injection (ICSI) and pregnancy outcomes.</p><p><strong>Materials and methods: </strong>A cohort of 196 non-syndromic MMAF patients was analyzed using whole exome sequencing (WES). Functional validation of candidate variants included immunofluorescence to assess protein expression and transmission electron microscopy (TEM) to identify ultrastructural abnormalities. Assisted reproductive therapy outcomes were also evaluated.</p><p><strong>Results: </strong>WES identified a recurrent homozygous frameshift variant in DRC1 NM_145038.5: c.109dup; p.(Gln37ProfsTer30) in four patients (2%), all of North African origin, none of whom suffer from PCD-related symptoms. The variant caused a complete absence of DRC1 protein in spermatozoa. TEM showed flagellar abnormalities, with 10% of axonemal sections revealing peripheral doublet dissociation, suggesting N-DRC instability. ICSI resulted in a 68.5% fertilization rate, with three out of four couples successfully delivering healthy children.</p><p><strong>Discussion and conclusion: </strong>The identification of a novel and recurrent pathogenic DRC1 variant broadens the mutation spectrum associated with MMAF. The absence of systemic PCD symptoms suggests that DRC1 deficiency may primarily affect spermatogenesis. Notably, the phenotypic spectrum might be influenced by the genetic background, varying across populations. Favorable ICSI outcomes, with a 68.5% fertilization rate and successful pregnancies in three out of four couples, highlight the effectiveness of assisted reproductive techniques for patients with this genetic defect.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942848","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":"Introduction to androgenetics: terminology, approaches, and impactful studies across 60 years","authors":"Arvand Akbari,&nbsp;Laura Kasak,&nbsp;Maris Laan","doi":"10.1111/andr.13835","DOIUrl":"10.1111/andr.13835","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Across six decades, androgenetics has consistently concentrated on discovering genetic causes and enhancing the molecular diagnostics of male infertility, disorders of sex development, and their broader implications on health, such as cancer and other comorbidities. Despite vast clinical knowledge, the training of andrologists often lacks fundamental basics in medical genetics. This work, as part of the Special Issue of Andrology “Genetics in Andrology”, provides the core terminology in medical genetics and technological advancements in genomics, required to understand the ever-progressing research in the field. It also gives an overview of study designs and approaches that have frequently led to discoveries in androgenetics. The rapid progress in the methodological toolbox in human genetics is illustrated by numerous examples of impactful androgenetic studies over 60 years, and their clinical implications.</p>\u0000 </section>\u0000 </div>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":"13 5","pages":"986-998"},"PeriodicalIF":3.2,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/andr.13835","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sulfur dioxide (SO₂) donors, a new gasotransmitter, improve erectile dysfunction after castration in a rat model.","authors":"Seyma Tetik-Rama, Didem Yilmaz-Oral, Damla Turkcan, Cetin Volkan Oztekin, Omer Faruk Kirlangic, Fatma Zeynep Kirlangic, Serap Gur","doi":"10.1111/andr.13839","DOIUrl":"https://doi.org/10.1111/andr.13839","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Androgen deprivation is associated with erectile dysfunction (ED). In different animal models, sulfur dioxide (SO&lt;sub&gt;2&lt;/sub&gt;) donors Na&lt;sub&gt;2&lt;/sub&gt;SO&lt;sub&gt;3&lt;/sub&gt; and NaHSO&lt;sub&gt;3&lt;/sub&gt; reduced oxidative stress, fibrosis, and inflammation which contribute to the pathogenesis of androgen deprivation-induced ED, however the effect of SO&lt;sub&gt;2&lt;/sub&gt; donors on ED in castrated rats were not known.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To investigate the therapeutic effect of SO&lt;sub&gt;2&lt;/sub&gt; donors, Na&lt;sub&gt;2&lt;/sub&gt;SO&lt;sub&gt;3&lt;/sub&gt;/NaHSO&lt;sub&gt;3&lt;/sub&gt;, on ED in castrated rat model.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;Sprague-Dawley male rats (n = 30) were divided into four groups; control, control-treated with Na&lt;sub&gt;2&lt;/sub&gt;SO&lt;sub&gt;3&lt;/sub&gt;/NaHSO&lt;sub&gt;3&lt;/sub&gt;, castrated, and castrated-treated with Na&lt;sub&gt;2&lt;/sub&gt;SO&lt;sub&gt;3&lt;/sub&gt;/NaHSO&lt;sub&gt;3&lt;/sub&gt;. Castration was induced by bilateral scrotal incisions. Four weeks after castration, rats were treated with Na&lt;sub&gt;2&lt;/sub&gt;SO&lt;sub&gt;3&lt;/sub&gt;/NaHSO&lt;sub&gt;3&lt;/sub&gt; (0.54/0.18 mmol/kg) intraperitoneally (i.p.) for 4 weeks. Intracavernosal pressure/mean arterial pressure ratio (ICP/MAP) and total ICP were measured to evaluate in vivo erectile responses in cavernosal tissue. In vitro relaxant and contractile responses were measured in all groups. Endothelial nitric oxide synthase (eNOS), neuronal NOS (nNOS), PI3 kinase p85 alpha + gamma (PI3K), protein kinase B (AKT 1/2/3), cysteine dioxygenase-1 (CDO), and aspartate aminotransferase (AAT) expressions and localizations were evaluated by Western blotting and immunohistochemical staining. The smooth muscle/collagen ratio was evaluated by Masson's trichrome staining.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Prostate (p &lt; 0.001) and penis weight (p &lt; 0.001), total serum testosterone (T) level (p &lt; 0.001), and in vivo erectile responses (p &lt; 0.001 at 7.5 and 5 V, p &lt; 0.05 at 2.5 V for ICP/MAP and total ICP) of castrated rats were decreased compared with control. SO&lt;sub&gt;2&lt;/sub&gt; donors improved reduced ICP/MAP ratio and total ICP (p &lt; 0.01 at 7.5, 5, and 2.5 V for ICP/MAP and total ICP) nitrergic (p &lt; 0.05 at 20 Hz), and endothelium-independent relaxation (p &lt; 0.05 at 1 nM, p &lt; 0.01 at 10 µM and 100 µM) in the castrated group. Decreased eNOS (p &lt; 0.01) and AKT (p &lt; 0.001) protein expressions in the castrated group were normalized by SO&lt;sub&gt;2&lt;/sub&gt;. SO&lt;sub&gt;2&lt;/sub&gt; donors partially restored the reduced smooth muscle/collagen ratio in the castrated group (p &lt; 0.001). The expressions and locations of nNOS, PI3K, CDO, and AAT proteins in penile tissue did not alter among all groups (p &gt; 0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion and conclusion: &lt;/strong&gt;SO&lt;sub&gt;2&lt;/sub&gt; donors significantly improve erectile functions and relaxation responses in a castrated rats via ameliorating endothelial damage and fibrosis. Androgen deprivation inhibits the AKT/eNOS signaling while SO&lt;sub&gt;2&lt;/sub&gt; activates this pathway. SO&lt;sub&gt;2&lt;/sub&gt; donors may be promising for the treatment of ED in hypoandrog","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942860","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":"6-Nitrodopamine is an endogenous mediator of rat seminal vesicles contractility.","authors":"Vivian Fuguhara, Gabriel Augusto Oliveira Stocco, José Britto-Júnior, Luiz Fernando Ribeiro, João Figueira Scarini, Fernanda Viviane Mariano, Valéria B de Souza, Andre Almeida Schenka, Edson Antunes, Gilberto De Nucci","doi":"10.1111/andr.13836","DOIUrl":"https://doi.org/10.1111/andr.13836","url":null,"abstract":"<p><strong>Background: </strong>6-Nitrodopamine (6-ND) released from rat vas deferens acts an endogenous modulator of vas deferens contractility.</p><p><strong>Objectives: </strong>To investigate whether rat isolated seminal vesicles (RISV) releases 6-ND, the mechanisms involved in the release, and the modulatory role of 6-ND on tissue contractility.</p><p><strong>Methods: </strong>Rat seminal vesicles were removed and placed in Krebs-Henseleit's solution at 37°C for 30 min, and an aliquot was used to analyze the concentrations of 6-ND, dopamine, noradrenaline, and adrenaline by liquid chromatography with tandem mass spectrometry (LC-MS/MS). The effect of mechanical removal of the epithelium and the effects of pre-incubation of RISV strips with N^ω-nitro-L-arginine methyl ester (L-NAME; in combination or not with L-arginine), tetrodotoxin (TTX), GKT137831, and hydrogen peroxide (H₂O₂) on 6-ND release were evaluated. For functional studies, RISV strips were mounted in an organ bath and tied to an isometric force transducer. The expressions of tyrosine hydroxylase and endothelial nitric oxide synthase (eNOS, type III NOS) were investigated by immunohistochemistry and/or fluorescence in situ hybridization (FISH).</p><p><strong>Results: </strong>6-ND was the major released catecholamine from RISV strips compared with noradrenaline, adrenaline, and dopamine. Epithelium removal significantly reduced the release of 6-ND, noradrenaline and dopamine. In RISV strips obtained from animals chronically treated with L-NAME, the 6-ND release significantly reduced. Pre-incubation with L-NAME reduced 6-ND release, which was partly restored by co-incubation with L-arginine. Pre-incubation with TTX had no effect on the release of any catecholamine, whereas GKT137831 and H₂O₂ significantly increased 6-ND release. All catecholamines produced concentration-dependent RISV contractions, but 6-ND was approximately 30× less potent than the others. 6-ND (0.1 nM) significantly potentiated noradrenaline-, adrenaline-, and dopamine-induced contractions, with such potentiations inhibited by TTX. Immunohistochemistry and FISH assays in RISV tissues identified tyrosine hydroxylase in epithelial cells and eNOS expression in both epithelial and endothelial cells.</p><p><strong>Discussion and conclusion: </strong>This is the first demonstration that epithelial-derived 6-ND modulates rat seminal vesicle contractility.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942847","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":"Role of GPR55 receptor in bovine sperm capacitation.","authors":"Raquel Lottero-Leconte, Angela Lara, Jessica Plaza, Camila Arroyo-Salvo, María Eugenia Bogetti, Amada Eugenia Ynsaurralde Rivolta, Franco Dellavalle, Fiamma Sengiali, Pablo Cetica, Sofía Rio, Lucia Zalazar, Andreína Cesari, Marcelo Miragaya, Sergio Morado, Silvina Perez-Martinez","doi":"10.1111/andr.13823","DOIUrl":"https://doi.org/10.1111/andr.13823","url":null,"abstract":"<p><strong>Background: </strong>Endocannabinoids like anandamide (AEA), among other lipids, are recognized signaling molecules that participate in reproductive events.</p><p><strong>Objectives: </strong>Our aims were to characterize orphan G protein-coupled receptor (GPR55) presence; investigate GPR55 activation by AEA and determine GPR55 role in the bovine sperm function.</p><p><strong>Materials and methods: </strong>GPR55 presence was assessed by immunocytochemistry. Protein kinase A (pPKA) and PKC (pPKC) substrates, pERK1/2, G/F-actin were determined by Western blotting, activation of RAC-1 by pull-down assay, F-actin and acrosomal exocytosis by fluorescence microscopy, sperm motility by optic microscopy and computer-aided sperm analysis and fertilizing ability by in vitro fertilization (IVF).</p><p><strong>Results: </strong>We detected GPR55 in spermatozoa at T0, after incubation in non-capacitating and capacitating (presence of AEA) conditions and upon release from oviductal epithelia. AEA induced an increase in pPKA and pPKC, while CID16020046 (CID), selective GPR55 antagonist, prevented this effect. Incubation with H89, PKA inhibitor, significantly decreased pPKC, while Gö6983, a PKC inhibitor, partially reduced pPKA. pPKA remained elevated at 15- and 45-min incubation, while pPKC decreased at 15 and increased at 45 min. CID prevented pPKC increase at 5 and 45 min and decreased pPKA at 45 min. RAC-1 and F-actin increase induced by AEA was prevented by CID. Variations in two progressive motility kinematic parameters were observed with AEA and/or CID. Sperm pretreatment with AEA increased the rate of cleaved embryos and CID prevented this effect.</p><p><strong>Discussion: </strong>We demonstrated that GPR55 activation by AEA induces time-dependent signaling pathways involving pPKA and pPKC during bovine sperm capacitation. AEA regulates actin polymerization through GPR55 activation, suggesting the receptor participates in cytoskeleton remodeling, and yielded higher IVF rates. Also, sperm pre-incubation with molecules like AEA involved in capacitation could improve the embryo development.</p><p><strong>Conclusion: </strong>We have demonstrated GPR55 presence in bovine spermatozoa. The regulation of PKA and PKC and of molecules associated with cytoskeletal dynamics, such as RAC-1 and actin, by GPR55 is closely related to sperm motility and acrosomal exocytosis.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920561","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":"A non-hormonal reversible contraceptive targeting GSK3α, a protein kinase, essential for epididymal sperm maturation.","authors":"Mustfa Kabi, Aditi Khamamkar, Kwaku Kyei-Baffour, Michel Weïwer, Srinivasan Vijayaraghavan, Souvik Dey","doi":"10.1111/andr.13838","DOIUrl":"https://doi.org/10.1111/andr.13838","url":null,"abstract":"<p><strong>Background and objectives: </strong>Epididymal transit renders key competence to mammalian spermatozoa for fertilizing eggs. Generally, the two paralogs of glycogen synthase kinase 3, GSK3α and GSK3β, functionally overlap except in testis and sperm. We showed that GSK3α is essential for epididymal sperm maturation and fertilization. Male infertility is the only phenotype of mice with a global or testis-specific knockout (KO) of Gsk3α. Their sperm maturation is impaired, and sperm cannot fertilize eggs in vitro and in vivo. This suggests that GSK3α is a \"male fertility kinase\" in mammals and that GSK3α-selective inhibitor is a potential male contraceptive.</p><p><strong>Materials and methods: </strong>A set of eight heterozygous Gsk3α(±) male mice received daily intraperitoneal injections of BRD0705, an isoform-selective GSK3α inhibitor, at 20 mg/kg body weight for 1 week. Five vehicle-treated and BRD0705-treated mice were tested for in vivo fertility and the remaining mice were sacrificed; their caudal spermatozoa were examined for motility and biochemical properties.</p><p><strong>Results: </strong>The treated mice did not sire any pups while the control group sired 46 pups with a normal gestation period of 19-23 days. Continued fertility testing up to 6 weeks post-treatment, showed that the treated mice regained fertility siring 56 pups, with 76 in the control group. Sperm motility was impaired, its abnormal morphology increased during epididymal transit, Adenosine triphosphate (ATP) levels were low, and tyrosine-phosphorylation of hexokinase was absent: these phenotypes imitated those observed in Gsk3α KO mice. Tyrosine²⁷⁹-phosphorylation of GSK3α was reduced in sperm from the treated mice showing that the GSK3α activity was inhibited. The altered sperm phenotypes returned to normal following recovery of fertility.</p><p><strong>Conclusions: </strong>Complete infertility resulted after 1 week of BRD0705-treatment and fertility recovered after cessation of the treatment. Work is ongoing to determine the minimum dose and treatment time and the testing of new compounds with increased selectivity and inhibitory activity against GSK3α.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920514","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}