AndrologyPub Date : 2025-07-11DOI: 10.1111/andr.70086
Aykut Gram, Murat Abay, Duygu Yaman Gram, Narin Liman, Linda Müller, Orsolya Balogh
{"title":"Modified cytoskeletal and extracellular matrix composition in the canine testis after long-acting gonadotropin-releasing hormone agonist deslorelin treatment.","authors":"Aykut Gram, Murat Abay, Duygu Yaman Gram, Narin Liman, Linda Müller, Orsolya Balogh","doi":"10.1111/andr.70086","DOIUrl":"https://doi.org/10.1111/andr.70086","url":null,"abstract":"<p><strong>Background: </strong>Long-acting gonadotropin-releasing hormone (GnRH) agonists are commonly used for fertility control in male dogs. Their effect on testicular histomorphology has not been clarified.</p><p><strong>Objectives: </strong>To elucidate the mechanisms underlying androgen withdrawal in response to long-acting GnRH agonist deslorelin 4.7 mg treatment on testicular histomorphology and key extracellular matrix (ECM) and cytoskeletal components.</p><p><strong>Materials and methods: </strong>Testes of deslorelin-treated dogs (n = 5) were evaluated at maximum downregulation of germinative and steroidogenic function, and compared with untreated (control) adult (n = 7) and prepubertal immature (n = 8) dogs. Morphological analysis was performed with Crossman's triple staining and periodic-acid-Schiff (PAS). Localization of smooth muscle α-actin (αSMA/ACTA2), desmin (DES), elastin (ELN), collagen type I (COL1A1), collagen type IV (COL4A1) was detected by immunohistochemistry.</p><p><strong>Results: </strong>Deslorelin treatment resulted in complete absence of germ cells except for spermatogonia. Crossman's triple staining identified thickening of peritubular connective tissue characterized by small infoldings toward the lumen of atrophied seminiferous tubules, and the expansion of interstitial area. PAS staining revealed a thickened basement membrane and phagosome-like particles within the seminiferous tubules. In control dogs, αSMA/ACTA2, DES, ELN, COL1A1, and COL4A1 were localized to blood vessels and the peritubular wall of seminiferous tubules. ELN, COL1A1, and COL4A1 were also found in stromal compartments. A similar localization pattern with signals within a thickened peritubular area was found in deslorelin-treated dogs. Prepubertal dogs had similar distribution but weaker signal intensity in the peritubular wall of seminiferous tubules. Positive area percentages of αSMA/ACTA2, DES, ELN, and COL4A1 were the highest in deslorelin-treated dogs, while COL1A1 was the lowest in control, intermediate in deslorelin-treated, and highest in prepubertal dogs.</p><p><strong>Conclusion: </strong>Deslorelin treatment caused infertility with accumulation of collagen (COL4A1, COL1A1) and deposition of αSMA/ACTA2, DES, and ELN within the thickened lamina propria surrounding seminiferous tubules. Peritubular myocytes maintained their smooth muscle phenotype despite androgen withdrawal. The immature testis had lower abundance of most cytoskeletal and ECM proteins.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607204","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 : 2025-07-11DOI: 10.1111/andr.70097
Berk Hazir, Hakan Bahadir Haberal, Meylis Artykov, Muhammet Irfan Donmez, Alicia López-Abad, Alessio Pecoraro, Beatriz Bañuelos Marco, Thomas Prudhomme, Alberto Piana, Daniar Osmonov, Murat Gul, Angelo Territo
{"title":"The effects of kidney transplantation on sex hormones, sperm parameters, and fertility rate in males: A systematic review.","authors":"Berk Hazir, Hakan Bahadir Haberal, Meylis Artykov, Muhammet Irfan Donmez, Alicia López-Abad, Alessio Pecoraro, Beatriz Bañuelos Marco, Thomas Prudhomme, Alberto Piana, Daniar Osmonov, Murat Gul, Angelo Territo","doi":"10.1111/andr.70097","DOIUrl":"https://doi.org/10.1111/andr.70097","url":null,"abstract":"<p><strong>Background: </strong>End-stage renal disease (ESRD) is reported to be associated with the impairment of sex hormones, including decreased testosterone levels and increased follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin levels. Additionally, patients with ESRD often experience impaired spermatogenesis, leading to infertility. However, variations in study methodologies and reported outcomes make it challenging to draw definitive conclusions. Therefore, this study aims to evaluate the effects of kidney transplantation (KT) on these issues, which can be useful in counseling male patients with ESRD.</p><p><strong>Methods: </strong>A systematic search was conducted in Web of Science, Medline (via PubMed), and Embase (via Scopus) to identify peer-reviewed studies evaluating the impact of KT on sex hormones and reproductive parameters. A systematic review (SR) was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. This review included English-language articles published between January 1975 and December 2024. Excluded from this search were reviews, editorials, book chapters, conference abstracts, case reports, and case series with up to four patients were excluded.</p><p><strong>Results: </strong>A total of 2939 publications were initially identified, and 23 studies met the inclusion criteria, comprising 738 patients for analysis. Most studies reported a significant increase in testosterone levels 3, 6, and 12 months post-KT. LH and prolactin levels exhibited a trend parallel to that of testosterone. A statistically significant decrease in LH levels was observed at both 1 and 12 months post-KT, while prolactin levels showed a significant reduction at all evaluated time points from 1 to 12 months. In contrast, FSH levels fluctuated over time and did not demonstrate statistical significance at any assessment point. Additionally, KT led to improvements in testis biopsy findings, and all categories of sperm parameters.</p><p><strong>Conclusion: </strong>This SR demonstrates that KT improves sex hormone levels, sperm parameters, and sexual function in male kidney recipients. However, to gain a more comprehensive understanding of the sexual health of male kidney recipients, the establishment of an international database with prospectively collected data is warranted.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607211","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 : 2025-07-11DOI: 10.1111/andr.70094
Asia Ingram, T Rajendra Kumar
{"title":"Gonadotropin storage and trafficking.","authors":"Asia Ingram, T Rajendra Kumar","doi":"10.1111/andr.70094","DOIUrl":"https://doi.org/10.1111/andr.70094","url":null,"abstract":"<p><strong>Background: </strong>Gonadotropins are synthesized in gonadotropes of the anterior pituitary, and they orchestrate reproductive function in vertebrates. LH and FSH share a common α-subunit that is non-covalently associated with a hormone - and receptor-specific β-subunit. Despite synthesized in the same cell, i.e., gonadotrope the trafficking and secretion patterns of LH and FSH are distinct. FSH is mostly constitutively secreted, whereas LH is stored in dense core granules and is released as a bolus via the regulated pathway in response to gonadotropin-releasing hormone.</p><p><strong>Objective: </strong>To comparatively review the storage and secretion patterns of gonadotropins in vertebrates.</p><p><strong>Materials and methods: </strong>Gonadotropin storage patterns are comparatively analyzed in vertebrates starting from primitive fish all the way up to higher mammals. The published work on gonadotropin trafficking/secretion patterns using in vitro and in vivo approaches is critically discussed.</p><p><strong>Results: </strong>Primitive fish (lampreys and hagfish) express a single gonadotropic hormone. From these early vertebrates, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) have evolved as two distinct hormones. In several species, including teleost fish, monohormonal gonadotropes are present that express either LH or FSH. In higher vertebrates, the majority of the gonadotropes (>90%) are bihormonal and contain both LH and FSH. Both in vitro (cell transfection and expression) and in vivo (transgenic mouse) studies identified that the LHβ caroboxy terminus heptapeptide is a gonadotrope-specific regulated pathway sorting determinant.</p><p><strong>Discussion: </strong>When FSH is genetically rerouted from the constitutive trafficking mode and is engineered (LHβ heptapeptide fused to FSHβ subunit) to exit via the regulated pathway in gonadotropes of transgenic mice, it resulted in enhanced ovulations due to suppression of atresia and apoptosis and increased pro-survival pathways in ovaries. However, rerouted FSH expressing male mice did not demonstrate any gain of function phenotypes.</p><p><strong>Conclusion: </strong>Understanding the basic molecular mechanisms of gonadotropin storage/trafficking and secretion may eventually lead to clinical benefits of enhancing female reproductive function and reproductive lifespan.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607203","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 : 2025-07-07DOI: 10.1111/andr.70085
Thamires Miyako Ito Sigole, Camila Reis Santos, Isabela Fiorentino Souza Nascimento, Erick J R Silva, Agnaldo Bruno Chies, Maria Angélica Spadella
{"title":"Adjuvant-induced arthritis induces epithelial proliferation and differential expression of SVS2 and SVS3 in the seminal vesicles.","authors":"Thamires Miyako Ito Sigole, Camila Reis Santos, Isabela Fiorentino Souza Nascimento, Erick J R Silva, Agnaldo Bruno Chies, Maria Angélica Spadella","doi":"10.1111/andr.70085","DOIUrl":"https://doi.org/10.1111/andr.70085","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is an inflammatory disease triggered by chronic and systemic activation of the immune system, with consequences for male fertility. However, the influence of RA on sexual accessory glands remains poorly investigated.</p><p><strong>Objectives: </strong>This study evaluated the late impact of adjuvant-induced arthritis (AIA) on the morphophysiology of the seminal vesicles and verified whether these effects can be influenced by androgen deprivation.</p><p><strong>Materials and methods: </strong>Adult male Wistar rats were allocated into four experimental groups and subjected to induction of AIA (via injection of Mycobacterium tuberculosis in the right hind paw), orchiectomy (ORX), both procedures (ORX/AIA), or neither (SHAM). Forty days after AIA induction, the seminal vesicles were processed for histopathological and morphometric-stereological analysis. Collagen deposition was measured, and immunostaining was conducted to determine PCNA, SVS2, and SVS3 expression. Serum testosterone was determined at 15 and 40 days after AIA induction.</p><p><strong>Results: </strong>Body mass and wet weight of the seminal vesicles decreased in the AIA-induced and orchiectomized groups, and testosterone levels decreased in the AIA group. Collagen deposition in the seminal vesicle stroma increased in the orchiectomized rats, but not in the AIA rats. Induction of AIA promoted cellular proliferation in the distal region of the seminal vesicles in both intact and orchiectomized rats, and levels of two significant secretory proteins in the vesicle also changed with AIA: SVS2 increased, while SVS3 decreased. Conversely, orchiectomy decreased the expression of both SVS2 and SVS3.</p><p><strong>Discussion: </strong>The late impact of AIA on seminal vesicle parameters appears to be compensated by an increase in epithelial cell proliferation and changes in secretory activity, in an androgen-dependent manner.</p><p><strong>Conclusion: </strong>The data suggest that transient arthritic hypoandrogenism and the direct action of joint inflammatory mediators may influence the seminal vesicle activity. Further research is required to better address the repercussions of arthritis on male fertility.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574682","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":"Pharmacokinetics, pharmacodynamics, and safety interaction study of tunodafil hydrochloride and alcohol: A randomized, blinded, placebo-controlled, three-cycle crossover study in Chinese healthy men.","authors":"Dingyuan Hu, Suping Niu, Fan Huang, Lu Jin, Qun Gu, Yanting Li, Chongyou Lee, Zhenwei Xie, Xiangxing Liu, Fang Men, Wenyan Zhao, Shuang Li, Yian Liu, Qian Wang, Huaying Fan, Jiaojiao Zhang, Shuangshuang Lin, Liming Chen, Yi Fang","doi":"10.1111/andr.70083","DOIUrl":"https://doi.org/10.1111/andr.70083","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to evaluate the pharmacodynamic effects of administering tunodafil hydrochloride with alcohol on blood pressure and heart rate in healthy Chinese males, and to investigate the mutual pharmacokinetic interactions and safety of the combination.</p><p><strong>Methods: </strong>The trial was a randomized, blinded, placebo-controlled, three-cycle crossover design, with one administration in each cycle and a 7-day washout interval between cycles. Eighteen healthy men were randomized to receive tunodafil hydrochloride with an alcoholic beverage, placebo with an alcoholic beverage, or tunodafil hydrochloride with a placebo beverage in each cycle. The primary endpoints included plasma concentrations of tunodafil, metabolite M459, and alcohol, as well as supine blood pressure and heart rate measurements. The secondary endpoint was the incidence of adverse events.</p><p><strong>Results: </strong>Pharmacokinetic results demonstrated that the combined drug and alcohol group did not affect plasma alcohol concentration compared to alcohol alone. However, co-administration led to increased systemic exposure of tunodafil and its metabolite M459: AUC<sub>0-∞</sub> rose by 42.89% and 28.75%, while C<sub>max</sub> increased by 74.46% and 39.32%, respectively, compared to the drug alone group. Pharmacodynamic analysis indicated that the reduction in blood pressure was primarily driven by alcohol consumption, with no significant additional effect from tunodafil co-administration. In contrast, heart rate elevation was notably amplified when both drug and alcohol were given together, exceeding the effects of either substance alone. Safety results reported 149 grade-one adverse events.</p><p><strong>Conclusion: </strong>The study concluded that tunodafil hydrochloride, when taken with alcohol, does not interfere with alcohol metabolism but moderately enhances the tunodafil and metabolite exposure. Alcohol remained the dominant factor in lowering blood pressure, while tunodafil contributed to an additive increase in heart rate. The combination does not significantly increase adverse events.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574683","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 : 2025-07-04DOI: 10.1111/andr.70096
Oriana Carcy, Sophie Desset, Tristan Dubos, Chloé Puceat, Maïssa Andrieux, Marine Compagnon, Gilles Sireta, Bruno Pereira, Florent Cachin, Aline V Probst, Christophe Tatout, Florence Brugnon, Hanae Pons-Rejraji
{"title":"New three-dimensional nuclear morphometry tool quantifies impact of slow freezing on sperm hypercondensed chromatin.","authors":"Oriana Carcy, Sophie Desset, Tristan Dubos, Chloé Puceat, Maïssa Andrieux, Marine Compagnon, Gilles Sireta, Bruno Pereira, Florent Cachin, Aline V Probst, Christophe Tatout, Florence Brugnon, Hanae Pons-Rejraji","doi":"10.1111/andr.70096","DOIUrl":"https://doi.org/10.1111/andr.70096","url":null,"abstract":"<p><strong>Background: </strong>Perm freezing compromises nuclear integrity. Standardized tools to assess three-dimensional (3D) chromatin alterations are lacking.</p><p><strong>Objectives: </strong>This study aimed to present a novel protocol for 3D nuclear morphometric analysis of human spermatozoa to measure slow freezing and thawing-induced alterations.</p><p><strong>Materials and methods: </strong>Human sperm cells were examined before and after freezing using a consistent 3D nuclear morphometric analysis protocol that distinguishes between live and dead spermatozoa. Morphometric assessments were performed by microscopy and image analysis with the NucleusJ2.0/NODeJ software, without introducing denaturing agents. The analysis included measurements of nuclear volume, elongation, flatness, and the volume of hypercondensed chromatin (Hc) regions, along with the relative fluorescence intensity of these zones (RHF intensity). Additional parameters evaluated comprised sperm vitality, motility, DNA fragmentation, and chromatin decondensation.</p><p><strong>Results: </strong>A quantitative analysis of 4919 sperm nuclei from 10 patients demonstrated significant modifications in the hypercondensed chromatin (Hc) zones, with a marked decrease in sperm vitality and motility (p < 0.001) and a significant increase in DNA fragmentation (p < 0.05). At the chromatin level, slow freezing induced a higher number of Hc zones per nucleus (p < 0.01), a reduction in the average volume of these zones (p < 0.0001), and a reduced relative fluorescence intensity (p < 0.01). Notably, these chromatin alterations were most pronounced in viable spermatozoa.</p><p><strong>Discussion and conclusion: </strong>This study is the first to provide standardized 3D nuclear morphometry measurements for human sperm, offering a novel biomarker to assess male fertility and cryopreservation susceptibility, with potential clinical applications for improving patient care. Slow freeze-thaw cycle induced significant alterations in sperm chromatin, disrupting nuclear organization and forming several smaller, less compacted hypercondensed chromatin zones.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558872","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 : 2025-07-04DOI: 10.1111/andr.70089
Isabel Barranco, Pablo Martínez-Díaz, Ana Parra, María José Martínez-Alborcia, Xiomara Lucas, Heriberto Rodríguez-Martínez, Jordi Roca
{"title":"Proteomic profiling of porcine seminal extracellular vesicles reveals potential in vivo fertility biomarkers.","authors":"Isabel Barranco, Pablo Martínez-Díaz, Ana Parra, María José Martínez-Alborcia, Xiomara Lucas, Heriberto Rodríguez-Martínez, Jordi Roca","doi":"10.1111/andr.70089","DOIUrl":"https://doi.org/10.1111/andr.70089","url":null,"abstract":"<p><strong>Background: </strong>Predicting male fertility in farm animals remains a challenge. Seminal plasma (SP) contains a high amount of heterogeneous seminal extracellular vesicles (sEVs), believed involved in reproductive processes and maybe key to understanding male fertility.</p><p><strong>Aims: </strong>To identify the sEV proteins that are differentially expressed between more and less fertile boars and that could be candidates for fertility biomarkers in boars used in artificial insemination (AI) programs.</p><p><strong>Materials and methods: </strong>Small (S) and large (L) sEV subsets from SP samples of AI boars with differences in fertility: high (H) or low (L) farrowing rate (FR) and large (L) or small (S) litter size (LS). The S- and L-sEV subsets were isolated by size exclusion chromatography and characterized according to the Minimal Information for Studies of Extracellular Vesicles (MISEV2023) guidelines. Proteomic analyses (three biological replicates per fertility group and sEV subset) were performed using a Bruker timsTOF fleX™ instrument with data-independent acquisition parallel accumulation-serial fragmentation (diaPASEF) technology.</p><p><strong>Results: </strong>A total of 470 and 726 proteins were quantified in S-sEVs and 1801 and 1834 proteins in L-sEVs from FR and LS boars, respectively. Differentially expressed sEV proteins (log<sub>2</sub>fold change ≥±1, p ≤ 0.05 and effect size d of Cohen >2.0) were found between the fertility groups: seven in S-sEVs and 52 in L-sEVs between H-FR and L-FR boars, and 47 in S-sEVs and 52 in L-sEVs between L-LS and S-LS boars. Many of these differentially expressed sEV proteins are involved in reproductive processes, particularly in sperm function and sperm-zona pellucida binding, but also in embryo development and implantation.</p><p><strong>Conclusions: </strong>The sEV proteome differs between more and less fertile boars, with many of the differentially expressed proteins known as involved in reproductive processes. This would suggest that sEVs may be involved in male fertility and that some of the differentially expressed sEV proteins could be potential fertility markers for AI boars.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144558873","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 : 2025-07-02DOI: 10.1111/andr.70093
Xinglin Qu, Yanqiu Lv, Yuyang Zhang, Lipeng Cao, Junzheng Zhang, Xuan Chen, Yi Jin
{"title":"Ubiquitin-mediated immunoglobulin-binding protein 1 degradation promotes autophagy and sperm capacitation in vitro.","authors":"Xinglin Qu, Yanqiu Lv, Yuyang Zhang, Lipeng Cao, Junzheng Zhang, Xuan Chen, Yi Jin","doi":"10.1111/andr.70093","DOIUrl":"https://doi.org/10.1111/andr.70093","url":null,"abstract":"<p><strong>Background: </strong>During sperm capacitation, post-translational modifications such as SUMOylation are crucial for maintaining protein homeostasis. Macroautophagy (autophagy) is essential for cellular and energy homeostasis, aiding in the survival of reproductive cells and protecting against ovarian aging. However, the role of autophagy in capacitated sperm remains unclear.</p><p><strong>Objectives: </strong>This study aimed to explore the relationship between small ubiquitin-like modifier 1 (SUMO1)-modified proteins and autophagy during sperm capacitation, focusing on the involvement of immunoglobulin-binding protein 1 (IGBP1) in the autophagy pathway.</p><p><strong>Materials and methods: </strong>Tandem mass spectrometry was employed to identify SUMO1-modified proteins in boar sperm before and after capacitation. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted to investigate the involvement of these proteins in autophagy, specifically examining the modification and degradation of IGBP1 via the ubiquitin-proteasome pathway (UPP). The regulatory role of the PKA-mTOR signaling axis on autophagy during capacitation was also examined.</p><p><strong>Results: </strong>A total of 229 SUMO1-modified proteins were identified in the non-capacitated group and 197 in the capacitated group, with 77 proteins unique to the non-capacitated state and 45 unique to the capacitated state. IGBP1 was found to be involved in the autophagy pathway, and its SUMO1 modification level significantly decreased after sperm capacitation, leading to its degradation via UPP. This degradation promoted autophagy and increased mTOR activity. The autophagy process involving IGBP1 was regulated by the upstream PKA-mTOR signaling axis. Additionally, a negative correlation between autophagy and apoptosis was observed during sperm capacitation, where the activation of autophagy enhanced capacitation and improved sperm-egg binding and embryonic development.</p><p><strong>Conclusion: </strong>The degradation of de-SUMOylated IGBP1 via UPP promotes sperm autophagy and enhances in vitro capacitation, providing new insights into the molecular mechanisms of sperm capacitation.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537809","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 : 2025-07-02DOI: 10.1111/andr.70092
Gabriele Birolini, Alessandro Bertini, Edoardo Pozzi, Massimiliano Raffo, Fausto Negri, Christian Corsini, Federico Belladelli, Alessia d'Arma, Luca Boeri, Francesco Montorsi, Andrea Salonia
{"title":"The educational level impact on treatment adherence in PDE5i-naïve men with erectile dysfunction: A real-life cross-sectional study.","authors":"Gabriele Birolini, Alessandro Bertini, Edoardo Pozzi, Massimiliano Raffo, Fausto Negri, Christian Corsini, Federico Belladelli, Alessia d'Arma, Luca Boeri, Francesco Montorsi, Andrea Salonia","doi":"10.1111/andr.70092","DOIUrl":"https://doi.org/10.1111/andr.70092","url":null,"abstract":"<p><strong>Introduction: </strong>The impact of the educational level on the adherence to phosphodiesterase type 5 inhibitors (PDE5i) among men with erectile dysfunction (ED) remains understudied. We aimed to investigate how the educational level influences patient's compliance to newly prescribed PDE5i in men with ED who had never previously used this class of drugs.</p><p><strong>Materials and methods: </strong>Complete data from 1264 consecutive PDE5i naive men presenting with new onset ED were retrospectively analyzed. Patients were grouped according to their educational level into low (elementary and/or secondary school education), mid (high school), and high (university degrees) educational levels. Baseline health significant comorbidities were scored with the Charlson comorbidity index (CCI). All patients completed the International Index of Erectile Function (IIEF) and the Beck depression inventory questionnaires at baseline. PDE5i were prescribed to all patients. Kaplan-Meier (KM) curves estimated the discontinuation free-survival (DFS) after stratification according to the educational level. Multivariable (MVA) Cox regression addressed the association between the educational level and PDE5is' discontinuation.</p><p><strong>Results: </strong>Of all, 160 (13%), 573 (45%), and 531 (42%) individuals depicted low, mid, and high educational level, respectively. Median (IQR) age and follow-up time were 51 (39-61) and 8.5 (5.9-11.3) years, respectively. Patients with higher educational level were more likely to be younger (49 vs. 56 years, p < 0.001), reporting lower BMI values (25 vs. 26.3 kg/m<sup>2</sup>, p < 0.001) and lower rates of CCI ≥ 1 (17% vs. 27%, p = 0.009), compared to their lower educational level counterparts. No significant differences were found in terms of duration of PDE5is assumption and IIEF-erectile function (IIEF-EF) across the groups. Kaplan-Meier survival analyses, stratified by the educational level, revealed significantly different patterns of PDE5i discontinuation-free survival across educational levels (log-rank test, p = 0.028). At multivariable Cox regression analysis, higher educational levels were significantly associated with PDE5i discontinuation, even after adjusting for age at presentation, IIEF-EF score, and relationship status simultaneously.</p><p><strong>Conclusions: </strong>Current findings demonstrated that the higher the educational level, the greater the PDE5is discontinuation rate in men with ED. These results highlight a particular aspect of patients' compliance with PDE5is, enabling improvements in real-life pharmacological management for ED.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537808","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 : 2025-07-02DOI: 10.1111/andr.70091
Richard Ivell, Bilal Tilumcu, Waleed Alhujaili, Ravinder Anand-Ivell
{"title":"Maternal, childhood and adolescent influences on Leydig cell functional capacity and circulating INSL3 concentration in young adults: Importance of childhood infections and body mass index.","authors":"Richard Ivell, Bilal Tilumcu, Waleed Alhujaili, Ravinder Anand-Ivell","doi":"10.1111/andr.70091","DOIUrl":"https://doi.org/10.1111/andr.70091","url":null,"abstract":"<p><strong>Background: </strong>The constitutive Leydig cell hormone insulin-like peptide 3 (INSL3) is considered a good estimate of the adult Leydig cell functional capacity and appears to remain relatively consistent throughout adult male life, only gradually declining into old age. Importantly, in younger men it appears to predict hypogonadism and hence later health and morbidity.</p><p><strong>Objectives: </strong>Here, we have used the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort of boys and young men to assess those factors during pregnancy, infancy, childhood, and adolescence, when the adult-type Leydig cell population is being established, which by association might influence the final circulating INSL3 concentration in young adulthood.</p><p><strong>Methods: </strong>A wide range of clinical, anthropometric and lifestyle parameters were assessed from up to 2000 boys and young men based on direct medical measurement and/or by targeted questionnaires. Scalar variables used bivariate correlation analysis, whereas comparative statistics, such as t-tests, were applied to categorical variables.</p><p><strong>Results: </strong>Maternal parameters, such as maternal smoking, gestational age, or being small for gestational age (SGA) appeared to have no association with adult INSL3 levels. Of all the parameters assessed, those with greatest impact on young adult Leydig cell status appeared to be childhood and adolescent body mass index (BMI) and early childhood infectious disease. Particularly, chickenpox in infancy had a marked and significant negative association with INSL3 (reduced by 10%-14%) at both 17 and 24 years. Being overweight (> 85th percentile) at 13 years was associated with a 20% reduction in young adult INSL3. In contrast, childhood and adolescent inflammatory factors and cigarette exposure appeared to have no long-lasting impact on adult Leydig cell status.</p><p><strong>Limitations: </strong>This retrospective cohort study is limited by relatively small numbers and by its correlative analysis. The hypotheses generated will need to be validated in more extensive, in-depth studies.</p><p><strong>Lay summary: </strong>The testis hormone INSL3 is considered a good estimate of the gonadal capacity to make testosterone. It is relatively constant throughout adult male life, only gradually declining into old age. Importantly, in younger men reduced INSL3 appears to predict hypogonadism and hence later health and morbidity. Whilst showing low within-individual variation, between individuals INSL3 can vary more than 10- up to 100-fold. The source of this variance is unknown but is believed to have its origin during childhood and adolescence. Analysis of data from the ALSPAC cohort implies that of various parameters assessed, only childhood and adolescent BMI as well as early infectious disease, in particular chickenpox, have any influence on young adult INSL3 concentration, respectively reducing circulating levels each by","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144551766","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}