Bocheng Tu, Kang Liu, Bo Wen, Peng Hu, Taotao Sun, Beining Li, Manan Sulaiman, Shujun Jiang, Tao Wang, Jihong Liu, Yang Luan
Background: Diabetes mellitus-induced erectile dysfunction (DMED) responds poorly to first-line treatments, necessitating the development of new therapeutic strategies. Relaxin-2 (RLX-2) plays a crucial role in protecting vascular endothelium, vasodilatation, and antifibrosis in various diseases. However, its effects and mechanisms on DMED remain unclear.
Objectives: To investigate the effects and mechanisms of RLX-2 on DMED rats in vivo and vitro.
Methods: For in vivo research, 30 Sprague-Dawley rats were allocated into three groups: control, DMED, and DMED + RLX-2. The induction of DMED in the rats was achieved through intraperitoneal administration of streptozotocin, with confirmation of ED status being conducted via the apomorphine test. Rats in the DMED + RLX-2 group received continuous RLX-2 treatment by osmotic pump. Following a 4-week treatment period, assessment of erectile function was carried out using cavernous manometry, and samples of corpus cavernosum tissues were procured for subsequent analysis. For in vitro research, human cardiac microvascular endothelial cells (HCMECs) were allocated into three groups: control, high glucose (HG, 40 mM), and HG + RLX-2. HCMECs were cultured for 6 days and treated with RLX-2 for 48 h before collection for subsequent experiments.
Results: In DMED rats, RLX-2 treatment partially improved erectile function. We observed relatively normalized functions of endothelial and smooth muscle cells with decreased levels of apoptosis and fibrosis in the penis. In vitro experiments also demonstrated the antihyperglycemic effects of RLX-2.
Conclusions: RLX-2 can protect endothelial and smooth muscle function, and inhibit aberrant apoptosis and fibrosis in the corpus cavernosum, thereby improving erectile function in DMED rats. This may provide a novel treatment for DMED.
{"title":"Relaxin-2 improves type I diabetes mellitus-induced erectile dysfunction in rats by protecting cavernous endothelial and smooth muscle function, and inhibiting penile fibrosis and apoptosis.","authors":"Bocheng Tu, Kang Liu, Bo Wen, Peng Hu, Taotao Sun, Beining Li, Manan Sulaiman, Shujun Jiang, Tao Wang, Jihong Liu, Yang Luan","doi":"10.1111/andr.13822","DOIUrl":"https://doi.org/10.1111/andr.13822","url":null,"abstract":"<p><strong>Background: </strong>Diabetes mellitus-induced erectile dysfunction (DMED) responds poorly to first-line treatments, necessitating the development of new therapeutic strategies. Relaxin-2 (RLX-2) plays a crucial role in protecting vascular endothelium, vasodilatation, and antifibrosis in various diseases. However, its effects and mechanisms on DMED remain unclear.</p><p><strong>Objectives: </strong>To investigate the effects and mechanisms of RLX-2 on DMED rats in vivo and vitro.</p><p><strong>Methods: </strong>For in vivo research, 30 Sprague-Dawley rats were allocated into three groups: control, DMED, and DMED + RLX-2. The induction of DMED in the rats was achieved through intraperitoneal administration of streptozotocin, with confirmation of ED status being conducted via the apomorphine test. Rats in the DMED + RLX-2 group received continuous RLX-2 treatment by osmotic pump. Following a 4-week treatment period, assessment of erectile function was carried out using cavernous manometry, and samples of corpus cavernosum tissues were procured for subsequent analysis. For in vitro research, human cardiac microvascular endothelial cells (HCMECs) were allocated into three groups: control, high glucose (HG, 40 mM), and HG + RLX-2. HCMECs were cultured for 6 days and treated with RLX-2 for 48 h before collection for subsequent experiments.</p><p><strong>Results: </strong>In DMED rats, RLX-2 treatment partially improved erectile function. We observed relatively normalized functions of endothelial and smooth muscle cells with decreased levels of apoptosis and fibrosis in the penis. In vitro experiments also demonstrated the antihyperglycemic effects of RLX-2.</p><p><strong>Conclusions: </strong>RLX-2 can protect endothelial and smooth muscle function, and inhibit aberrant apoptosis and fibrosis in the corpus cavernosum, thereby improving erectile function in DMED rats. This may provide a novel treatment for DMED.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799113","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}
Clara Lazzaretti, Mohammed Akli Ayoub, Livio Casarini
Background: Gonadotropins are glycoprotein hormones fundamental in the endocrine regulation of reproduction. They act on structurally similar members of G protein-coupled receptors (GPCRs) expressed exclusively in the gonads and support gametogenesis, sex steroid synthesis, and pregnancy. While it is a common opinion that the gonadotropin receptors act as a single molecule entity (monomer), increasing evidence underlines the formation of molecular complexes involving multiple receptors.
Objectives: To review current knowledge of membrane receptor-receptor interactions in reproduction.
Results and discussion: Homo/heteromers of gonadotropin receptors may act as allosteric modulators, act as biased agonist and/or cooperate in sustaining intracellular signals fundamental to support reproduction. Technical limitations lead to in vitro data that require to be confirmed in vivo to figure out the physiological impact of gonadotropin receptor assemblies.
Conclusions: Gonadotropin receptor homo/heteromers provide a new field of research that deserves attention for possible clinical and therapeutic implications in physiology and pathophysiology.
{"title":"G protein-coupled receptor-receptor interactions in gonadal physiology.","authors":"Clara Lazzaretti, Mohammed Akli Ayoub, Livio Casarini","doi":"10.1111/andr.13821","DOIUrl":"https://doi.org/10.1111/andr.13821","url":null,"abstract":"<p><strong>Background: </strong>Gonadotropins are glycoprotein hormones fundamental in the endocrine regulation of reproduction. They act on structurally similar members of G protein-coupled receptors (GPCRs) expressed exclusively in the gonads and support gametogenesis, sex steroid synthesis, and pregnancy. While it is a common opinion that the gonadotropin receptors act as a single molecule entity (monomer), increasing evidence underlines the formation of molecular complexes involving multiple receptors.</p><p><strong>Objectives: </strong>To review current knowledge of membrane receptor-receptor interactions in reproduction.</p><p><strong>Results and discussion: </strong>Homo/heteromers of gonadotropin receptors may act as allosteric modulators, act as biased agonist and/or cooperate in sustaining intracellular signals fundamental to support reproduction. Technical limitations lead to in vitro data that require to be confirmed in vivo to figure out the physiological impact of gonadotropin receptor assemblies.</p><p><strong>Conclusions: </strong>Gonadotropin receptor homo/heteromers provide a new field of research that deserves attention for possible clinical and therapeutic implications in physiology and pathophysiology.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799110","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}
Vittoria Sterpi, Elena Ricci, Francesca Chiaffarino, Francesco Fedele, Giovanna Esposito, Fabio Parazzini, Paola Viganò, Sonia Cipriani
Background: Over the past few decades, several studies have found that semen quality parameters have steadily declined over time. Many hypotheses have been made to explain this finding, among which a sedentary lifestyle has been investigated. To synthesize the current evidence, we performed a systematic review of published papers reporting on the relationship between sedentary habits and semen parameters.
Methods: Embase and PubMed were systematically searched for papers published in English up to May 2023. We included all full-text observational papers that reported the relationship between sedentariness and semen parameters. Article selection adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.
Results: Sixteen observational studies were ultimately included, six in healthy men and ten in men from Fertility Clinics. They encompassed a total of 13,509 men, with 9877 being healthy men and 3632 presenting at Fertility Clinics for initial assessment. In terms of semen volume, no association emerged in the six studies involving healthy men: however, results in men referring to fertility clinics mainly showed no association, with one indicating a decline and one higher volume. Twelve studies did not report differences in sperm concentration, while one study in men from Fertility Clinics and two in healthy men observed a decline in this parameter with increasing time spent on TV watching or sedentary posture in spare time. Total sperm count was found to be similar across groups of inactivity, except for one study that showed a significant decrease when men from Fertility Clinics spent more time watching TV. No significant differences were reported in sperm motility across all studies, with only one study, among those addressing sperm morphology, indicating a lower percentage of normal forms in men watching TV more than 3 h per day. Finally, three studies conducted in men referring to Fertility Clinics analyzed the sperm DNA fragmentation index. Two of these studies found a higher DNA fragmentation index in men spending more time per day in a sitting posture.
Conclusions: This review suggests a weak association between time spent sitting during spare time and sperm concentration, but the findings are inconsistent, highlighting the need for further research.
{"title":"The sitting men: A systematic review of spare and working time exposure to sedentariness in relation to semen parameters.","authors":"Vittoria Sterpi, Elena Ricci, Francesca Chiaffarino, Francesco Fedele, Giovanna Esposito, Fabio Parazzini, Paola Viganò, Sonia Cipriani","doi":"10.1111/andr.13816","DOIUrl":"https://doi.org/10.1111/andr.13816","url":null,"abstract":"<p><strong>Background: </strong>Over the past few decades, several studies have found that semen quality parameters have steadily declined over time. Many hypotheses have been made to explain this finding, among which a sedentary lifestyle has been investigated. To synthesize the current evidence, we performed a systematic review of published papers reporting on the relationship between sedentary habits and semen parameters.</p><p><strong>Methods: </strong>Embase and PubMed were systematically searched for papers published in English up to May 2023. We included all full-text observational papers that reported the relationship between sedentariness and semen parameters. Article selection adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.</p><p><strong>Results: </strong>Sixteen observational studies were ultimately included, six in healthy men and ten in men from Fertility Clinics. They encompassed a total of 13,509 men, with 9877 being healthy men and 3632 presenting at Fertility Clinics for initial assessment. In terms of semen volume, no association emerged in the six studies involving healthy men: however, results in men referring to fertility clinics mainly showed no association, with one indicating a decline and one higher volume. Twelve studies did not report differences in sperm concentration, while one study in men from Fertility Clinics and two in healthy men observed a decline in this parameter with increasing time spent on TV watching or sedentary posture in spare time. Total sperm count was found to be similar across groups of inactivity, except for one study that showed a significant decrease when men from Fertility Clinics spent more time watching TV. No significant differences were reported in sperm motility across all studies, with only one study, among those addressing sperm morphology, indicating a lower percentage of normal forms in men watching TV more than 3 h per day. Finally, three studies conducted in men referring to Fertility Clinics analyzed the sperm DNA fragmentation index. Two of these studies found a higher DNA fragmentation index in men spending more time per day in a sitting posture.</p><p><strong>Conclusions: </strong>This review suggests a weak association between time spent sitting during spare time and sperm concentration, but the findings are inconsistent, highlighting the need for further research.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794324","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}
Marion Bendayan, Florence Boitrelle, Safouane Maurens-Hamdi
Congenital absence of the vas deferens (CAVD) is a syndrome with a heterogeneous presentation: bilateral (CBAVD) or unilateral (CUAVD), complete or partial and associated or not with other anomalies of the male urogenital system. A turning point came in 1968 when CBAVD was associated with cystic fibrosis and its CFTR gene mutations. Genetic studies then revealed that a minority of CBAVD but a majority of CUAVD are CFTR-independent. In the literature, reference is classically made to two sources from the 18th and 19th century: Hunter and Reverdin. This scarcity prompted us to look for additional observations of CAVD. By a meticulous bibliographical search, we identified a corpus of 10 European observations (8 CUAVD and 2 CBAVD) some of them richly illustrated. They were collected between 1755 and 1876 throughout adult men autopsies. We also provided their primary and unambiguous sources. Analysis of the reported data revealed some interesting facts: both CBAVD cases were unlikely linked to cystic fibrosis and half of CUAVD cases were associated with an ipsilateral kidney absence, suggesting a CFTR-independent pathophysiology. Moreover, the anatomical details of the anomalies raise interesting embryological questions we have tried to address in the light of current data. This work made it possible to identify new historical sources dealing with male genital tract pathologies. It sheds light on the origins of andrology and opens up interesting prospects for research and education in the field.
{"title":"Congenital absence of vas deferens: Anatomical and embryological inputs from a series of autopsies reported in Europe throughout the 18th and 19th century.","authors":"Marion Bendayan, Florence Boitrelle, Safouane Maurens-Hamdi","doi":"10.1111/andr.13815","DOIUrl":"https://doi.org/10.1111/andr.13815","url":null,"abstract":"<p><p>Congenital absence of the vas deferens (CAVD) is a syndrome with a heterogeneous presentation: bilateral (CBAVD) or unilateral (CUAVD), complete or partial and associated or not with other anomalies of the male urogenital system. A turning point came in 1968 when CBAVD was associated with cystic fibrosis and its CFTR gene mutations. Genetic studies then revealed that a minority of CBAVD but a majority of CUAVD are CFTR-independent. In the literature, reference is classically made to two sources from the 18th and 19th century: Hunter and Reverdin. This scarcity prompted us to look for additional observations of CAVD. By a meticulous bibliographical search, we identified a corpus of 10 European observations (8 CUAVD and 2 CBAVD) some of them richly illustrated. They were collected between 1755 and 1876 throughout adult men autopsies. We also provided their primary and unambiguous sources. Analysis of the reported data revealed some interesting facts: both CBAVD cases were unlikely linked to cystic fibrosis and half of CUAVD cases were associated with an ipsilateral kidney absence, suggesting a CFTR-independent pathophysiology. Moreover, the anatomical details of the anomalies raise interesting embryological questions we have tried to address in the light of current data. This work made it possible to identify new historical sources dealing with male genital tract pathologies. It sheds light on the origins of andrology and opens up interesting prospects for research and education in the field.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794322","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}
Deborah I Bunin, Kyuri Kim, Toufan Parman, Janet Gahagen, Mary B Zelinski, Tiffany Adevai, Christina Wang, Liang Tang, Lalitha Iyer, Aaron Endsley, Diana L Blithe, Min S Lee
Background: Dimethandrolone undecanoate (DMAU) is under development as a single agent hormonal male contraceptive. DMAU is a prodrug hydrolyzed by esterase(s) to the active metabolite dimethandrolone (DMA) which has dual androgenic and progestogenic actions. Phase 1 clinical trial results show DMAU to be well-tolerated as an oral contraceptive in healthy men; however, delivery of DMAU as a long-acting injectable rather than a daily oral formulation would provide user compliance benefits and address oral bioavailability concerns.
Objective: To assess the safety, pharmacokinetics (PK), and long-acting contraceptive potential of DMAU in male non-human primates (NHP) when delivered as an injectable or oral formulation.
Materials and methods: DMAU was administered to cynomolgus macaques orally for 9 months or as five weekly intramuscular (IM) injections and to rhesus macaques as a single IM injection. Evaluations of safety, fertility indicators, and serum levels of DMAU and DMA were followed > 2 years post-dose.
Results: Repeat dose oral and IM administrations were well-tolerated with no significant toxicological findings. Dramatic reductions in serum testosterone concentration occurred within days of administration followed by sustained suppression of additional fertility indicators (e.g., serum inhibin B, sperm count, and testicular spermatogenesis). Slight body weight increases and reductions in testes weight also occurred. Repeat DMAU injections resulted in DMA serum concentrations above the lower limit of quantification (1 ng/mL) for > 500 days. DMAU PK parameters increased with increasing IM dose, while dose dependence was not seen for serum DMA concentrations suggesting a depot effect with a reservoir of non-circulating prodrug remaining at the injection site which gets slowly hydrolyzed to DMA and absorbed into circulation. Testosterone levels and spermatogenesis returned by the end of the recovery period.
Conclusions: Nonclinical safety, PK, and pharmacodynamic data in male NHP demonstrate the safe, well-tolerated, long-acting, and reversible contraceptive potential of injectable DMAU.
{"title":"Evaluation of dimethandrolone undecanoate in non-human primates as a candidate for long-acting injectable male contraceptive.","authors":"Deborah I Bunin, Kyuri Kim, Toufan Parman, Janet Gahagen, Mary B Zelinski, Tiffany Adevai, Christina Wang, Liang Tang, Lalitha Iyer, Aaron Endsley, Diana L Blithe, Min S Lee","doi":"10.1111/andr.13819","DOIUrl":"10.1111/andr.13819","url":null,"abstract":"<p><strong>Background: </strong>Dimethandrolone undecanoate (DMAU) is under development as a single agent hormonal male contraceptive. DMAU is a prodrug hydrolyzed by esterase(s) to the active metabolite dimethandrolone (DMA) which has dual androgenic and progestogenic actions. Phase 1 clinical trial results show DMAU to be well-tolerated as an oral contraceptive in healthy men; however, delivery of DMAU as a long-acting injectable rather than a daily oral formulation would provide user compliance benefits and address oral bioavailability concerns.</p><p><strong>Objective: </strong>To assess the safety, pharmacokinetics (PK), and long-acting contraceptive potential of DMAU in male non-human primates (NHP) when delivered as an injectable or oral formulation.</p><p><strong>Materials and methods: </strong>DMAU was administered to cynomolgus macaques orally for 9 months or as five weekly intramuscular (IM) injections and to rhesus macaques as a single IM injection. Evaluations of safety, fertility indicators, and serum levels of DMAU and DMA were followed > 2 years post-dose.</p><p><strong>Results: </strong>Repeat dose oral and IM administrations were well-tolerated with no significant toxicological findings. Dramatic reductions in serum testosterone concentration occurred within days of administration followed by sustained suppression of additional fertility indicators (e.g., serum inhibin B, sperm count, and testicular spermatogenesis). Slight body weight increases and reductions in testes weight also occurred. Repeat DMAU injections resulted in DMA serum concentrations above the lower limit of quantification (1 ng/mL) for > 500 days. DMAU PK parameters increased with increasing IM dose, while dose dependence was not seen for serum DMA concentrations suggesting a depot effect with a reservoir of non-circulating prodrug remaining at the injection site which gets slowly hydrolyzed to DMA and absorbed into circulation. Testosterone levels and spermatogenesis returned by the end of the recovery period.</p><p><strong>Conclusions: </strong>Nonclinical safety, PK, and pharmacodynamic data in male NHP demonstrate the safe, well-tolerated, long-acting, and reversible contraceptive potential of injectable DMAU.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794323","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}
Giuseppe Grande, Andrea Graziani, Luca De Toni, Federica Finocchi, Adriano Presciutti, Sara Corrò, Alberto Ferlin, Andrea Garolla
Background: The most prevalent sexually transmitted disease in the world has the human papillomavirus (HPV) as its etiological agent.
Objectives: To evaluate the prevalence of previous and actual HPV infection and the clinical manifestations in unselected males.
Materials and methods: A total of 718 males participating to a surveillance program were asked to complete a study visit at our unit, including semen collection, balanopreputial sulcus swab, and blood collection for total anti-HPV immunoglobulin G (IgG). When HPV-DNA was detected, we performed HPV fluorescence in situ hybridization, oral and anal swab, and penoscopy. Because previous studies demonstrated a very high risk for HPV infection in subjects with history of HPV-induced lesions, with a partner with diagnosed HPV infection or reporting couple infertility or sexual promiscuity and an increase of the risk in males having sex with males, in subjects with unprotected sexual intercourses or in heavy smokers, patients were therefore stratified according to the presence of these known risk factors (RFs).
Results: Actual HPV infection was detected in 401/718 subjects (55.85%). Oral HPV-DNA was reported in 80 subjects and anal HPV infection in 52 subjects. Anti-HPV IgG antibodies have been detected in 288 subjects. The overall prevalence of HPV exposition, considering actual and/or previous infection was 77.99%. Among infected men, high-risk HPV genotypes were detected in 66.08%. A total of 514 subjects were considered as the RF population, while 150 were classified in the non-RF population. There was a significantly higher prevalence of condylomatosis (odds ratio [OR] 4.07) and of seminal infection (OR 6.22) in the RF group.
Discussion and conclusion: These data represent an alert for the healthcare system to perform informative and screening campaigns for HPV infection in males and to promote HPV vaccination both in young people and for adult males with RF for HPV infections.
{"title":"Prevalence of HPV infection in the general population of young and adult males in Italy.","authors":"Giuseppe Grande, Andrea Graziani, Luca De Toni, Federica Finocchi, Adriano Presciutti, Sara Corrò, Alberto Ferlin, Andrea Garolla","doi":"10.1111/andr.13817","DOIUrl":"https://doi.org/10.1111/andr.13817","url":null,"abstract":"<p><strong>Background: </strong>The most prevalent sexually transmitted disease in the world has the human papillomavirus (HPV) as its etiological agent.</p><p><strong>Objectives: </strong>To evaluate the prevalence of previous and actual HPV infection and the clinical manifestations in unselected males.</p><p><strong>Materials and methods: </strong>A total of 718 males participating to a surveillance program were asked to complete a study visit at our unit, including semen collection, balanopreputial sulcus swab, and blood collection for total anti-HPV immunoglobulin G (IgG). When HPV-DNA was detected, we performed HPV fluorescence in situ hybridization, oral and anal swab, and penoscopy. Because previous studies demonstrated a very high risk for HPV infection in subjects with history of HPV-induced lesions, with a partner with diagnosed HPV infection or reporting couple infertility or sexual promiscuity and an increase of the risk in males having sex with males, in subjects with unprotected sexual intercourses or in heavy smokers, patients were therefore stratified according to the presence of these known risk factors (RFs).</p><p><strong>Results: </strong>Actual HPV infection was detected in 401/718 subjects (55.85%). Oral HPV-DNA was reported in 80 subjects and anal HPV infection in 52 subjects. Anti-HPV IgG antibodies have been detected in 288 subjects. The overall prevalence of HPV exposition, considering actual and/or previous infection was 77.99%. Among infected men, high-risk HPV genotypes were detected in 66.08%. A total of 514 subjects were considered as the RF population, while 150 were classified in the non-RF population. There was a significantly higher prevalence of condylomatosis (odds ratio [OR] 4.07) and of seminal infection (OR 6.22) in the RF group.</p><p><strong>Discussion and conclusion: </strong>These data represent an alert for the healthcare system to perform informative and screening campaigns for HPV infection in males and to promote HPV vaccination both in young people and for adult males with RF for HPV infections.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765579","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}
Wesley H Chou, Cameron Chalker, Alexandra O Sokolova, Sudhir Isharwal
Prostate cancer remains a lethal disease for many men. Knowledge of genetic contributions to this condition has increasingly been used in its management. In this narrative review, we summarize various genetic alterations and syndromes associated with prostate cancer, including hereditary breast and ovarian cancer syndrome, Lynch syndrome, and hereditary prostate cancer, among others. Indications for germline testing are reviewed, as well as incorporation of genetic data at different phases of management for prostate cancer, such as screening and monitoring, and treatment of localized and metastatic disease.
{"title":"Prostate cancer and genetic contributions.","authors":"Wesley H Chou, Cameron Chalker, Alexandra O Sokolova, Sudhir Isharwal","doi":"10.1111/andr.13812","DOIUrl":"https://doi.org/10.1111/andr.13812","url":null,"abstract":"<p><p>Prostate cancer remains a lethal disease for many men. Knowledge of genetic contributions to this condition has increasingly been used in its management. In this narrative review, we summarize various genetic alterations and syndromes associated with prostate cancer, including hereditary breast and ovarian cancer syndrome, Lynch syndrome, and hereditary prostate cancer, among others. Indications for germline testing are reviewed, as well as incorporation of genetic data at different phases of management for prostate cancer, such as screening and monitoring, and treatment of localized and metastatic disease.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749577","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}
Lara Tamburrino, Giulia Traini, Maria Emanuela Ragosta, Sara Dabizzi, Sara Vezzani, Flavia Scarpa, Linda Vignozzi, Elisabetta Baldi, Sara Marchiani
Background: Sperm cryopreservation is a consolidate option for long-term male fertility preservation. The freezing/thawing procedure causes detrimental effects to spermatozoa, including damage to viability, motility, membrane composition, and DNA, whereas the effect on sperm chromatin compaction is less studied.
Objectives: The primary aim of this study was to investigate the impact of cryopreservation on sperm chromatin compaction. Furthermore, the effect of cryopreservation on sperm parameters (motility, viability, chromatin compaction, and DNA fragmentation) was also assessed in relation to the storage time in liquid nitrogen.
Materials and methods: Semen samples, collected from 126 (92 normozoospermic and 34 oligozoospermic) patients undergoing routine semen analysis in the Andrology Laboratory of Careggi University Hospital of Florence, were frozen by conventional fast vapor freezing method. Sperm motility, viability, kinematic parameters (by computer-aided sperm analysis [CASA]), chromatin compaction (by staining with both aniline blue [AB] and Chromomycin A3 [CMA3]), and sperm DNA fragmentation (sDF, by TUNEL/Propidium Iodide [PI]) were evaluated before freezing and after thawing at different timepoints.
Results: After 7 days of storage, a significant decline in sperm motility, viability, and kinematics parameters, as well as a significant increase in the percentage of sperm positivity to CMA3, AB, and sDF, were observed. It is noteworthy that while motility and viability decreased in almost all subjects, the increase in CMA3 and AB positivity was observed in 68.0% and 79.2% of samples, respectively. A progressive deterioration of sperm motility and viability, less evident for chromatin structure, was observed at longer times of storage (28 and 180 days).
Discussion: Our results indicate that freezing/thawing procedures can alter chromatin structure. A reduction in protamine content and/or a modification in chromatin assembly can be hypothesized. Furthermore, the length of storage in liquid nitrogen appears to progressively affect sperm parameters, although it should be confirmed in larger cohort of subjects.
Conclusion: Current sperm cryopreservation protocols need to be improved with new strategies and personalized procedures aimed to minimize the damage.
{"title":"Semen cryopreservation and storage in liquid nitrogen: Impact on chromatin compaction.","authors":"Lara Tamburrino, Giulia Traini, Maria Emanuela Ragosta, Sara Dabizzi, Sara Vezzani, Flavia Scarpa, Linda Vignozzi, Elisabetta Baldi, Sara Marchiani","doi":"10.1111/andr.13806","DOIUrl":"https://doi.org/10.1111/andr.13806","url":null,"abstract":"<p><strong>Background: </strong>Sperm cryopreservation is a consolidate option for long-term male fertility preservation. The freezing/thawing procedure causes detrimental effects to spermatozoa, including damage to viability, motility, membrane composition, and DNA, whereas the effect on sperm chromatin compaction is less studied.</p><p><strong>Objectives: </strong>The primary aim of this study was to investigate the impact of cryopreservation on sperm chromatin compaction. Furthermore, the effect of cryopreservation on sperm parameters (motility, viability, chromatin compaction, and DNA fragmentation) was also assessed in relation to the storage time in liquid nitrogen.</p><p><strong>Materials and methods: </strong>Semen samples, collected from 126 (92 normozoospermic and 34 oligozoospermic) patients undergoing routine semen analysis in the Andrology Laboratory of Careggi University Hospital of Florence, were frozen by conventional fast vapor freezing method. Sperm motility, viability, kinematic parameters (by computer-aided sperm analysis [CASA]), chromatin compaction (by staining with both aniline blue [AB] and Chromomycin A3 [CMA3]), and sperm DNA fragmentation (sDF, by TUNEL/Propidium Iodide [PI]) were evaluated before freezing and after thawing at different timepoints.</p><p><strong>Results: </strong>After 7 days of storage, a significant decline in sperm motility, viability, and kinematics parameters, as well as a significant increase in the percentage of sperm positivity to CMA3, AB, and sDF, were observed. It is noteworthy that while motility and viability decreased in almost all subjects, the increase in CMA3 and AB positivity was observed in 68.0% and 79.2% of samples, respectively. A progressive deterioration of sperm motility and viability, less evident for chromatin structure, was observed at longer times of storage (28 and 180 days).</p><p><strong>Discussion: </strong>Our results indicate that freezing/thawing procedures can alter chromatin structure. A reduction in protamine content and/or a modification in chromatin assembly can be hypothesized. Furthermore, the length of storage in liquid nitrogen appears to progressively affect sperm parameters, although it should be confirmed in larger cohort of subjects.</p><p><strong>Conclusion: </strong>Current sperm cryopreservation protocols need to be improved with new strategies and personalized procedures aimed to minimize the damage.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749740","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}
Rossella Mazzilli, Danilo Cimadomo, Federica Innocenti, Marilena Taggi, Greta Chiara Cermisoni, Sara Ginesi, Lisa Dovere, Laura Albricci, Maurizio Guido, Maria Rosaria Campitiello, Susanna Ferrero, Antonio Capalbo, Alberto Vaiarelli, Filippo Maria Ubaldi, Alberto Ferlin, Laura Rienzi, Gianluca Gennarelli
Objective: To examine the association between semen parameters, assessed according to World Health Organization (WHO)-2021 criteria, and paternal body mass index (BMI) and age, with embryological and clinical outcomes in ICSI cycles involving preimplantation genetic testing for aneuploidy (PGT-A).
Design: Retrospective study at a private in vitro fertilization (IVF) clinic.
Intervention: We performed trophectoderm biopsy, and comprehensive chromosome testing to report uniform aneuploidies and vitrified-warmed euploid single-blastocyst-transfers. Regression analyses adjusted for relevant confounders were conducted to outline putative associations of semen analysis and characteristics and paternal BMI and age with all embryological/clinical outcomes.
Results: Maternal age was the only significant confounding variable affecting euploidy blastocyst rate (EBR) (primary embryological outcome). When categorized, motility < 5th-percentile (-2.5%, 95%CI -4.9 to -0.2%, p = 0.03), concentration plus morphology < 5th-percentile (-2.7%,95%CI -4.8 to -0.6%, p = 0.01), concentration plus morphology plus motility < 5th-percentile (-4.0%,95%CI -5.5 to -2.6%, p < 0.01), obstructive-azoospermia [OA] (-5.5%,95%CI -9 to -2%, p = 0.02) and non-obstructive azoospermia (NOA) (-5.8%,95%CI -10.9 to -0.6%, p = 0.03) showed significantly lower results compared to all parameters > 5th-percentile. Furthermore, after adjusting for maternal age and the number of metaphase-II-oocytes inseminated, the only significant confounding variable affecting the chance of obtaining ≥ 1 live birth among completed cycles (primary clinical outcome) was basal and post sperm processing motility. When categorized, concentration plus morphology plus motility < 5th-percentile (multivariable-OR: 0.73, 95%CI 0.58-0.93, p = 0.01) and OA (multivariable-OR: 0.47, 95%CI 0.24-0.92, p = 0.03) showed significantly lower chances compared to all parameters > 5th-percentile. Advanced paternal age (defined as > 44 years) was associated only with lower day 5-blastocyst and Gardner's AA-grade (i.e., top quality) blastocyst rates.
Conclusions: This comprehensive analysis provides IVF professionals with useful figures to counsel infertile couples about their chances of success, taking into account the impact of semen characteristics and paternal BMI and age. These estimates are valuable for personalized decision-making about the most effective reproductive strategies to adopt, especially not underestimating male factor, by improving sperm concentration and motility whenever possible before assisted reproductive technologies.
{"title":"A WHO 2021-based comprehensive scheme outlining sperm parameters' associations with IVF outcomes in PGT-A cycles.","authors":"Rossella Mazzilli, Danilo Cimadomo, Federica Innocenti, Marilena Taggi, Greta Chiara Cermisoni, Sara Ginesi, Lisa Dovere, Laura Albricci, Maurizio Guido, Maria Rosaria Campitiello, Susanna Ferrero, Antonio Capalbo, Alberto Vaiarelli, Filippo Maria Ubaldi, Alberto Ferlin, Laura Rienzi, Gianluca Gennarelli","doi":"10.1111/andr.13811","DOIUrl":"https://doi.org/10.1111/andr.13811","url":null,"abstract":"<p><strong>Objective: </strong>To examine the association between semen parameters, assessed according to World Health Organization (WHO)-2021 criteria, and paternal body mass index (BMI) and age, with embryological and clinical outcomes in ICSI cycles involving preimplantation genetic testing for aneuploidy (PGT-A).</p><p><strong>Design: </strong>Retrospective study at a private in vitro fertilization (IVF) clinic.</p><p><strong>Subjects: </strong>3101 couples undergoing 4013 intracytoplasmic sperm injection (ICSI) + PGT-A cycles with own-oocytes (years 2013-2021).</p><p><strong>Intervention: </strong>We performed trophectoderm biopsy, and comprehensive chromosome testing to report uniform aneuploidies and vitrified-warmed euploid single-blastocyst-transfers. Regression analyses adjusted for relevant confounders were conducted to outline putative associations of semen analysis and characteristics and paternal BMI and age with all embryological/clinical outcomes.</p><p><strong>Results: </strong>Maternal age was the only significant confounding variable affecting euploidy blastocyst rate (EBR) (primary embryological outcome). When categorized, motility < 5<sup>th</sup>-percentile (-2.5%, 95%CI -4.9 to -0.2%, p = 0.03), concentration plus morphology < 5<sup>th</sup>-percentile (-2.7%,95%CI -4.8 to -0.6%, p = 0.01), concentration plus morphology plus motility < 5<sup>th</sup>-percentile (-4.0%,95%CI -5.5 to -2.6%, p < 0.01), obstructive-azoospermia [OA] (-5.5%,95%CI -9 to -2%, p = 0.02) and non-obstructive azoospermia (NOA) (-5.8%,95%CI -10.9 to -0.6%, p = 0.03) showed significantly lower results compared to all parameters > 5<sup>th</sup>-percentile. Furthermore, after adjusting for maternal age and the number of metaphase-II-oocytes inseminated, the only significant confounding variable affecting the chance of obtaining ≥ 1 live birth among completed cycles (primary clinical outcome) was basal and post sperm processing motility. When categorized, concentration plus morphology plus motility < 5<sup>th</sup>-percentile (multivariable-OR: 0.73, 95%CI 0.58-0.93, p = 0.01) and OA (multivariable-OR: 0.47, 95%CI 0.24-0.92, p = 0.03) showed significantly lower chances compared to all parameters > 5<sup>th</sup>-percentile. Advanced paternal age (defined as > 44 years) was associated only with lower day 5-blastocyst and Gardner's AA-grade (i.e., top quality) blastocyst rates.</p><p><strong>Conclusions: </strong>This comprehensive analysis provides IVF professionals with useful figures to counsel infertile couples about their chances of success, taking into account the impact of semen characteristics and paternal BMI and age. These estimates are valuable for personalized decision-making about the most effective reproductive strategies to adopt, especially not underestimating male factor, by improving sperm concentration and motility whenever possible before assisted reproductive technologies.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749571","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}
Sheng Xin, Wen Song, Jiaquan Mao, Peng Hu, Zhong Chen, Jihong Liu, Xiaodong Song, Qian Fang, Kai Cui
Background: Among erectile dysfunction (ED) caused by metabolic abnormalities, diabetes mellitus-induced ED (DMED) progresses rapidly, manifests with severe symptoms, and shows reduced responsiveness to conventional medications. Hyperglycemia in the corpus cavernosum has been linked to the induction of both ferroptosis and oxidative stress, which are mediated by nuclear factor E2 related factor 2 (Nrf2). Hesperidin (Hes), a flavonoid compound, has been revealed to activate Nrf2 in certain diabetic complications, yet the efficacy of Hes on DMED and the specific mechanism remain unclear.
Objectives: To elucidate the potential mechanism and efficacy of Hes in regulating Nrf2-mediated ferroptosis and oxidative stress in DMED.
Materials and methods: DMED rats were constructed through the intraperitoneal injection of streptozotocin (STZ), partially supplemented with Hes. In parallel, in vitro research utilized human umbilical vein endothelial cells (HUVECs), with glucose addition to simulating a high glucose (HG) environment, and induced with Hes or ML385 (an Nrf2 inhibitor). Penile tissues and HUVECs were harvested for subsequent analyses.
Results: The results of this study indicate that Hes partially reversed the impaired erectile function. The expression of Nrf2, glutathione peroxidase 4 (GPX4), and heme oxygenase-1 (HO-1) in the corpus cavernosum elevated after supplementing with Hes, resulted in an inhibition in ferroptosis and oxidative stress. Moreover, the quantity and function of erectile effector cells were restored, and cavernous fibrosis was ameliorated. In HG-induced HUVECs, Hes ameliorated Nrf2-mediated ferroptosis and oxidative stress, effects which ML385 partially reversed.
Conclusions: Hes exerts a therapeutic effect on DMED rats and a regulatory mechanism on the Nrf2-HO-1/GPX4 axis, concurrently revitalizing endothelial and smooth muscle cells, and diminishing fibrosis. Our study provides robust preclinical evidence for employing Hes in treating DMED.
{"title":"Therapeutic potential of hesperidin in diabetes mellitus-induced erectile dysfunction through Nrf2-mediated ferroptosis and oxidative stress.","authors":"Sheng Xin, Wen Song, Jiaquan Mao, Peng Hu, Zhong Chen, Jihong Liu, Xiaodong Song, Qian Fang, Kai Cui","doi":"10.1111/andr.13814","DOIUrl":"https://doi.org/10.1111/andr.13814","url":null,"abstract":"<p><strong>Background: </strong>Among erectile dysfunction (ED) caused by metabolic abnormalities, diabetes mellitus-induced ED (DMED) progresses rapidly, manifests with severe symptoms, and shows reduced responsiveness to conventional medications. Hyperglycemia in the corpus cavernosum has been linked to the induction of both ferroptosis and oxidative stress, which are mediated by nuclear factor E2 related factor 2 (Nrf2). Hesperidin (Hes), a flavonoid compound, has been revealed to activate Nrf2 in certain diabetic complications, yet the efficacy of Hes on DMED and the specific mechanism remain unclear.</p><p><strong>Objectives: </strong>To elucidate the potential mechanism and efficacy of Hes in regulating Nrf2-mediated ferroptosis and oxidative stress in DMED.</p><p><strong>Materials and methods: </strong>DMED rats were constructed through the intraperitoneal injection of streptozotocin (STZ), partially supplemented with Hes. In parallel, in vitro research utilized human umbilical vein endothelial cells (HUVECs), with glucose addition to simulating a high glucose (HG) environment, and induced with Hes or ML385 (an Nrf2 inhibitor). Penile tissues and HUVECs were harvested for subsequent analyses.</p><p><strong>Results: </strong>The results of this study indicate that Hes partially reversed the impaired erectile function. The expression of Nrf2, glutathione peroxidase 4 (GPX4), and heme oxygenase-1 (HO-1) in the corpus cavernosum elevated after supplementing with Hes, resulted in an inhibition in ferroptosis and oxidative stress. Moreover, the quantity and function of erectile effector cells were restored, and cavernous fibrosis was ameliorated. In HG-induced HUVECs, Hes ameliorated Nrf2-mediated ferroptosis and oxidative stress, effects which ML385 partially reversed.</p><p><strong>Conclusions: </strong>Hes exerts a therapeutic effect on DMED rats and a regulatory mechanism on the Nrf2-HO-1/GPX4 axis, concurrently revitalizing endothelial and smooth muscle cells, and diminishing fibrosis. Our study provides robust preclinical evidence for employing Hes in treating DMED.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715287","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}