Shu-Wei Luo, Le Tang, Dai Zhou, Hao Bo, Li-Qing Fan
Continuous self-renewal and differentiation of spermatogonial stem cells (SSCs) is vital for maintenance of adult spermatogenesis. Although several spermatogonial stem cell regulators have been extensively investigated in rodents, regulatory mechanisms of human SSC self-renewal and differentiation have not been fully established. We analyzed single-cell sequencing data from the human testis and found that forkhead box P4 (FOXP4) expression gradually increased with development of SSCs. Further analysis of its expression patterns in human testicular tissues revealed that FOXP4 specifically marks a subset of spermatogonia with stem cell potential. Conditional inactivation of FOXP4 in human SSC lines suppressed SSC proliferation and significantly activated apoptosis. FOXP4 expressions were markedly suppressed in tissues with dysregulated spermatogenesis. These findings imply that FOXP4 is involved in human SSC proliferation, which will help elucidate on the mechanisms controlling the fate decisions in human SSCs.
{"title":"FOXP4 promotes proliferation of human spermatogonial stem cells.","authors":"Shu-Wei Luo, Le Tang, Dai Zhou, Hao Bo, Li-Qing Fan","doi":"10.4103/aja202254","DOIUrl":"https://doi.org/10.4103/aja202254","url":null,"abstract":"<p><p>Continuous self-renewal and differentiation of spermatogonial stem cells (SSCs) is vital for maintenance of adult spermatogenesis. Although several spermatogonial stem cell regulators have been extensively investigated in rodents, regulatory mechanisms of human SSC self-renewal and differentiation have not been fully established. We analyzed single-cell sequencing data from the human testis and found that forkhead box P4 (FOXP4) expression gradually increased with development of SSCs. Further analysis of its expression patterns in human testicular tissues revealed that FOXP4 specifically marks a subset of spermatogonia with stem cell potential. Conditional inactivation of FOXP4 in human SSC lines suppressed SSC proliferation and significantly activated apoptosis. FOXP4 expressions were markedly suppressed in tissues with dysregulated spermatogenesis. These findings imply that FOXP4 is involved in human SSC proliferation, which will help elucidate on the mechanisms controlling the fate decisions in human SSCs.</p>","PeriodicalId":8483,"journal":{"name":"Asian Journal of Andrology","volume":"25 3","pages":"322-330"},"PeriodicalIF":2.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/73/e8/AJA-25-322.PMC10226497.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9534743","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}
Xiu-Yun Li, Mei-Hua Zhang, Zhao-Wen Chen, Bin Zhang, Gang Bai, He-Feng Wang
This study assessed the effects of a simulated high-altitude environment on the reproductive system of prepubertal male rats and the reversibility of these effects upon return to a normal environment. Three-week-old male Wistar rats were randomly allocated to 4 groups that were exposed to different conditions: a normal environment for 6 weeks and 12 weeks, respectively, hypobaric hypoxia for 6 weeks, and hypobaric hypoxia for 6 weeks followed by a normal environment for 6 weeks. Multiple pathophysiological parameters were evaluated at the histological, endocrine, and molecular levels. Hypobaric hypoxia exposure for 6 weeks during the prepubertal phase significantly altered physiological parameters, body functions, blood indices, and reproductive potential. Six weeks after returning to a normal environment, the damaged reproductive functions partially recovered due to compensatory mechanisms. However, several changes were not reversed after returning to a normal environment for 6 weeks, including disorders of body development and metabolism, increased red blood cells, increased fasting blood glucose, abnormal blood lipid metabolism, decreased testicular and epididymis weights, abnormal reproductive hormone levels, excessive apoptosis of reproductive cells, and decreased sperm concentration. In summary, a hypobaric hypoxic environment significantly impaired the reproductive function of prepubertal male rats, and a return to normal conditions during the postpubertal phase did not fully recover these impairments.
{"title":"Male reproductive system and simulated high-altitude environment: preliminary results in rats.","authors":"Xiu-Yun Li, Mei-Hua Zhang, Zhao-Wen Chen, Bin Zhang, Gang Bai, He-Feng Wang","doi":"10.4103/aja202290","DOIUrl":"https://doi.org/10.4103/aja202290","url":null,"abstract":"<p><p>This study assessed the effects of a simulated high-altitude environment on the reproductive system of prepubertal male rats and the reversibility of these effects upon return to a normal environment. Three-week-old male Wistar rats were randomly allocated to 4 groups that were exposed to different conditions: a normal environment for 6 weeks and 12 weeks, respectively, hypobaric hypoxia for 6 weeks, and hypobaric hypoxia for 6 weeks followed by a normal environment for 6 weeks. Multiple pathophysiological parameters were evaluated at the histological, endocrine, and molecular levels. Hypobaric hypoxia exposure for 6 weeks during the prepubertal phase significantly altered physiological parameters, body functions, blood indices, and reproductive potential. Six weeks after returning to a normal environment, the damaged reproductive functions partially recovered due to compensatory mechanisms. However, several changes were not reversed after returning to a normal environment for 6 weeks, including disorders of body development and metabolism, increased red blood cells, increased fasting blood glucose, abnormal blood lipid metabolism, decreased testicular and epididymis weights, abnormal reproductive hormone levels, excessive apoptosis of reproductive cells, and decreased sperm concentration. In summary, a hypobaric hypoxic environment significantly impaired the reproductive function of prepubertal male rats, and a return to normal conditions during the postpubertal phase did not fully recover these impairments.</p>","PeriodicalId":8483,"journal":{"name":"Asian Journal of Andrology","volume":"25 3","pages":"426-432"},"PeriodicalIF":2.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d7/20/AJA-25-426.PMC10226506.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9541585","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}
Enhanced recovery after surgery (ERAS) measures have not been systematically applied in transurethral surgery for benign prostatic hyperplasia (BPH). This study was performed on patients with BPH who required surgical intervention. From July 2019 to June 2020, the ERAS program was applied to 248 patients, and the conventional program was applied to 238 patients. After 1 year of follow-up, the differences between the ERAS group and the conventional group were evaluated. The ERAS group had a shorter time of urinary catheterization compared with the conventional group (mean ± standard deviation [s.d.]: 1.0 ± 0.4 days vs 2.7 ± 0.8 days, P < 0.01), and the pain (mean ± s.d.) was significantly reduced through postoperative hospitalization days (PODs) 0-2 (POD 0: 1.7 ± 0.8 vs 2.4 ± 1.0, P < 0.01; POD 1: 1.6 ± 0.9 vs 3.5 ± 1.3, P < 0.01; POD 2: 1.2 ± 0.7 vs 3.0 ± 1.3, P < 0.01). No statistically significant difference was found in the rate of postoperative complications, such as postoperative bleeding (P = 0.79), urinary retention (P = 0.40), fever (P = 0.55), and readmission (P = 0.71). The hospitalization cost of the ERAS group was similar to that of the conventional group (mean ± s.d.: 16 927.8 ± 5808.1 Chinese Yuan [CNY] vs 17 044.1 ± 5830.7 CNY, P =0.85). The International Prostate Symptom Scores (IPSS) and quality of life (QoL) scores in the two groups were also similar when compared at 1 month, 3 months, 6 months, and 12 months after discharge. The ERAS program we conducted was safe, repeatable, and efficient. In conclusion, patients undergoing the ERAS program experienced less postoperative stress than those undergoing the conventional program.
{"title":"Enhanced recovery after surgery in transurethral surgery for benign prostatic hyperplasia.","authors":"Jing Zhou, Zhu-Feng Peng, Pan Song, Lu-Chen Yang, Zheng-Huan Liu, Shuai-Ke Shi, Lin-Chun Wang, Jun-Hao Chen, Liang-Ren Liu, Qiang Dong","doi":"10.4103/aja202267","DOIUrl":"https://doi.org/10.4103/aja202267","url":null,"abstract":"<p><p>Enhanced recovery after surgery (ERAS) measures have not been systematically applied in transurethral surgery for benign prostatic hyperplasia (BPH). This study was performed on patients with BPH who required surgical intervention. From July 2019 to June 2020, the ERAS program was applied to 248 patients, and the conventional program was applied to 238 patients. After 1 year of follow-up, the differences between the ERAS group and the conventional group were evaluated. The ERAS group had a shorter time of urinary catheterization compared with the conventional group (mean ± standard deviation [s.d.]: 1.0 ± 0.4 days vs 2.7 ± 0.8 days, P < 0.01), and the pain (mean ± s.d.) was significantly reduced through postoperative hospitalization days (PODs) 0-2 (POD 0: 1.7 ± 0.8 vs 2.4 ± 1.0, P < 0.01; POD 1: 1.6 ± 0.9 vs 3.5 ± 1.3, P < 0.01; POD 2: 1.2 ± 0.7 vs 3.0 ± 1.3, P < 0.01). No statistically significant difference was found in the rate of postoperative complications, such as postoperative bleeding (P = 0.79), urinary retention (P = 0.40), fever (P = 0.55), and readmission (P = 0.71). The hospitalization cost of the ERAS group was similar to that of the conventional group (mean ± s.d.: 16 927.8 ± 5808.1 Chinese Yuan [CNY] vs 17 044.1 ± 5830.7 CNY, P =0.85). The International Prostate Symptom Scores (IPSS) and quality of life (QoL) scores in the two groups were also similar when compared at 1 month, 3 months, 6 months, and 12 months after discharge. The ERAS program we conducted was safe, repeatable, and efficient. In conclusion, patients undergoing the ERAS program experienced less postoperative stress than those undergoing the conventional program.</p>","PeriodicalId":8483,"journal":{"name":"Asian Journal of Andrology","volume":"25 3","pages":"356-360"},"PeriodicalIF":2.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1b/1e/AJA-25-356.PMC10226510.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9542434","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}
Sahil Kumar, Elise Bertin, Cormac O'Dwyer, Amir Khorrami, Richard Wassersug, Smita Mukherjee, Neeraj Mehra, Marshall Dahl, Krista Genoway, Alexander G Kavanagh
Transmasculine individuals, considering whether to undergo total hysterectomy with bilateral salpingectomy, have the option to have a concomitant oophorectomy. While studies have evaluated hormone changes following testosterone therapy initiation, most of those patients have not undergone oophorectomy. Data are currently limited to support health outcomes regarding the decision to retain or remove the ovaries. We performed a retrospective chart review of transmasculine patients maintained on high-dose testosterone therapy at a single endocrine clinic in Vancouver, British Columbia, Canada. Twelve transmasculine individuals who underwent bilateral oophorectomy and had presurgical and postsurgical serum data were included. We identified 12 transmasculine subjects as controls, who were on testosterone therapy and did not undergo oophorectomy, but additionally matched to the first group by age, testosterone dosing regimen, and body mass index. There was a statistically significant decrease in the estradiol levels of case subjects postoophorectomy, when compared to presurgical estradiol levels (P = 0.02). There was no significant difference between baseline estradiol levels between control and case subjects; however, the difference in estradiol levels at follow-up measurements was significant (P = 0.03). Total testosterone levels did not differ between control and case subjects at baseline and follow-up (both P > 0.05). Our results demonstrate that oophorectomy further attenuates estradiol levels below what is achieved by high-dose exogenous testosterone alone. Correlated clinical outcomes, such as impacts on bone health, were not available. The clinical implications of oophorectomy versus ovarian retention on endocrinological and overall health outcomes are currently limited.
{"title":"Serum estradiol levels decrease after oophorectomy in transmasculine individuals on testosterone therapy.","authors":"Sahil Kumar, Elise Bertin, Cormac O'Dwyer, Amir Khorrami, Richard Wassersug, Smita Mukherjee, Neeraj Mehra, Marshall Dahl, Krista Genoway, Alexander G Kavanagh","doi":"10.4103/aja202262","DOIUrl":"https://doi.org/10.4103/aja202262","url":null,"abstract":"<p><p>Transmasculine individuals, considering whether to undergo total hysterectomy with bilateral salpingectomy, have the option to have a concomitant oophorectomy. While studies have evaluated hormone changes following testosterone therapy initiation, most of those patients have not undergone oophorectomy. Data are currently limited to support health outcomes regarding the decision to retain or remove the ovaries. We performed a retrospective chart review of transmasculine patients maintained on high-dose testosterone therapy at a single endocrine clinic in Vancouver, British Columbia, Canada. Twelve transmasculine individuals who underwent bilateral oophorectomy and had presurgical and postsurgical serum data were included. We identified 12 transmasculine subjects as controls, who were on testosterone therapy and did not undergo oophorectomy, but additionally matched to the first group by age, testosterone dosing regimen, and body mass index. There was a statistically significant decrease in the estradiol levels of case subjects postoophorectomy, when compared to presurgical estradiol levels (P = 0.02). There was no significant difference between baseline estradiol levels between control and case subjects; however, the difference in estradiol levels at follow-up measurements was significant (P = 0.03). Total testosterone levels did not differ between control and case subjects at baseline and follow-up (both P > 0.05). Our results demonstrate that oophorectomy further attenuates estradiol levels below what is achieved by high-dose exogenous testosterone alone. Correlated clinical outcomes, such as impacts on bone health, were not available. The clinical implications of oophorectomy versus ovarian retention on endocrinological and overall health outcomes are currently limited.</p>","PeriodicalId":8483,"journal":{"name":"Asian Journal of Andrology","volume":"25 3","pages":"309-313"},"PeriodicalIF":2.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/8b/e1/AJA-25-309.PMC10226504.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9543118","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}
Bang-Wei Che, Pan Chen, Ying Yu, Wei Li, Tao Huang, Wen-Jun Zhang, Sheng-Han Xu, Jun He, Miao Liu, Kai-Fa Tang
Coronavirus disease 2019 (COVID-19) has yet to be proven to alter male reproductive function, particularly in the majority of mild/asymptomatic patients. The purpose of this study was to explore whether mild/asymptomatic COVID-19 affects semen quality and sex-related hormone levels. To find suitable comparative studies, a systematic review and meta-analysis was done up to January 22, 2022, by using multiple databases (Web of Science, PubMed, and Embase). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to identify and choose the studies. Meta-analysis was used to examine the semen parameters and sex-related hormones of mild/asymptomatic COVID-19 patients before and after infection. The effects of semen collection time, fever, and intensity of verification on semen following infection were also investigated. A total of 13 studies (n = 770) were included in the analysis, including three case-control studies, six pre-post studies, and four single-arm studies. A meta-analysis of five pre-post studies showed that after infection with COVID-19, sperm concentration (I2 = 0; P = 0.003), total sperm count (I2 = 46.3%; P = 0.043), progressive motility (I2 = 50.0%; P < 0.001), total sperm motility (I2 = 76.1%; P = 0.047), and normal sperm morphology (I2 = 0; P = 0.001) decreased. Simultaneously, a systematic review of 13 studies found a significant relationship between semen collection time after infection, inflammation severity, and semen parameter values, with fever having only bearing on semen concentration. Furthermore, there was no significant difference in sex-related hormone levels before and after infection in mild/asymptomatic patients. Mild/asymptomatic COVID-19 infection had a significant effect on semen quality in the short term. It is recommended to avoid initiating a pregnancy during this period of time.
{"title":"Effects of mild/asymptomatic COVID-19 on semen parameters and sex-related hormone levels in men: a systematic review and meta-analysis.","authors":"Bang-Wei Che, Pan Chen, Ying Yu, Wei Li, Tao Huang, Wen-Jun Zhang, Sheng-Han Xu, Jun He, Miao Liu, Kai-Fa Tang","doi":"10.4103/aja202250","DOIUrl":"https://doi.org/10.4103/aja202250","url":null,"abstract":"<p><p>Coronavirus disease 2019 (COVID-19) has yet to be proven to alter male reproductive function, particularly in the majority of mild/asymptomatic patients. The purpose of this study was to explore whether mild/asymptomatic COVID-19 affects semen quality and sex-related hormone levels. To find suitable comparative studies, a systematic review and meta-analysis was done up to January 22, 2022, by using multiple databases (Web of Science, PubMed, and Embase). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to identify and choose the studies. Meta-analysis was used to examine the semen parameters and sex-related hormones of mild/asymptomatic COVID-19 patients before and after infection. The effects of semen collection time, fever, and intensity of verification on semen following infection were also investigated. A total of 13 studies (n = 770) were included in the analysis, including three case-control studies, six pre-post studies, and four single-arm studies. A meta-analysis of five pre-post studies showed that after infection with COVID-19, sperm concentration (I<sup>2</sup> = 0; P = 0.003), total sperm count (I<sup>2</sup> = 46.3%; P = 0.043), progressive motility (I<sup>2</sup> = 50.0%; P < 0.001), total sperm motility (I<sup>2</sup> = 76.1%; P = 0.047), and normal sperm morphology (I<sup>2</sup> = 0; P = 0.001) decreased. Simultaneously, a systematic review of 13 studies found a significant relationship between semen collection time after infection, inflammation severity, and semen parameter values, with fever having only bearing on semen concentration. Furthermore, there was no significant difference in sex-related hormone levels before and after infection in mild/asymptomatic patients. Mild/asymptomatic COVID-19 infection had a significant effect on semen quality in the short term. It is recommended to avoid initiating a pregnancy during this period of time.</p>","PeriodicalId":8483,"journal":{"name":"Asian Journal of Andrology","volume":"25 3","pages":"382-388"},"PeriodicalIF":2.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/98/05/AJA-25-382.PMC10226500.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9542409","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}
Meng-Ya Sun, Yang Peng, Da-Wei Liu, Ke Wang, Huan-Jun Wang, Jian Guan
CG) and hemorrhage, detected by multiparametric magnetic resonance imaging (MRI)
{"title":"Ectopic prostate tissue at the bladder trigone accompanied by cystitis glandularis and hemorrhage detected by multiparametric MRI.","authors":"Meng-Ya Sun, Yang Peng, Da-Wei Liu, Ke Wang, Huan-Jun Wang, Jian Guan","doi":"10.4103/aja202279","DOIUrl":"https://doi.org/10.4103/aja202279","url":null,"abstract":"CG) and hemorrhage, detected by multiparametric magnetic resonance imaging (MRI)","PeriodicalId":8483,"journal":{"name":"Asian Journal of Andrology","volume":"25 3","pages":"438-439"},"PeriodicalIF":2.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/01/94/AJA-25-438.PMC10226512.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9541166","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}
Xiao-Hao Ruan, Da Huang, Xiao-Ling Lin, Zu-Jun Fang, Qiang Ding, Yi-Shuo Wu, Rong Na
carriers. BRCA2 -mutant prostate tumors were associated with high-grade disease and progression to metastatic castration-resistant PCa, affecting treatment effectiveness. 4,5 Some recent studies suggested that pathogenic mutations in the PCCR of BRCA2 were related to a higher PCa risk than mutations elsewhere in the gene, by 1.78–2.34-fold hazard ratio (HR). 6,7 Both studies evaluated the hypothesis of the PCCR in BRCA2 carrier cohorts of Caucasians or nonrace-specific populations under either a prospective or retrospective design. However, whether PCCR mutations are associated with PCa risk at the population level is still unknown. In addition, the relationship between BRCA2 regions and PCa has been poorly studied in the Chinese population. We conducted the present study in two cohorts, the UK Biobank (UKB) prospective cohort and a Chinese PCa cohort. The study was approved by the North West Multi-centre Research Ethics Committee in Manchester, UK (IRAS project ID: 299116; approval No. 66813), and the Institutional Review Board of Shanghai Huashan Hospital in Shanghai, China (approval No. KY2011-009). Written informed consent was obtained from each participant. The UKB is a large-scale biomedical database containing genetic and phenotype information from a prospective cohort study. 8 We established a prospective cohort of 83 181 European who had not been diagnosed with PCa at recruitment and had not developed any other types of cancers during follow-up (last follow-up in January 2022). A PCa diagnosis was identified from national cancer registries and self-report records (International Classification of Diseases [ICD] 10: C61). PCa-related death ( i.e. , lethal PCa) information was identified from death registries. The Chinese PCa cohort was a retrospective case-only cohort of 235 PCa patients who had undergone whole-exome sequencing (WES) of
{"title":"Germline mutations in 5' to c.7914 of <i>BRCA2</i> significantly increase risk of prostate cancer.","authors":"Xiao-Hao Ruan, Da Huang, Xiao-Ling Lin, Zu-Jun Fang, Qiang Ding, Yi-Shuo Wu, Rong Na","doi":"10.4103/aja202277","DOIUrl":"https://doi.org/10.4103/aja202277","url":null,"abstract":"carriers. BRCA2 -mutant prostate tumors were associated with high-grade disease and progression to metastatic castration-resistant PCa, affecting treatment effectiveness. 4,5 Some recent studies suggested that pathogenic mutations in the PCCR of BRCA2 were related to a higher PCa risk than mutations elsewhere in the gene, by 1.78–2.34-fold hazard ratio (HR). 6,7 Both studies evaluated the hypothesis of the PCCR in BRCA2 carrier cohorts of Caucasians or nonrace-specific populations under either a prospective or retrospective design. However, whether PCCR mutations are associated with PCa risk at the population level is still unknown. In addition, the relationship between BRCA2 regions and PCa has been poorly studied in the Chinese population. We conducted the present study in two cohorts, the UK Biobank (UKB) prospective cohort and a Chinese PCa cohort. The study was approved by the North West Multi-centre Research Ethics Committee in Manchester, UK (IRAS project ID: 299116; approval No. 66813), and the Institutional Review Board of Shanghai Huashan Hospital in Shanghai, China (approval No. KY2011-009). Written informed consent was obtained from each participant. The UKB is a large-scale biomedical database containing genetic and phenotype information from a prospective cohort study. 8 We established a prospective cohort of 83 181 European who had not been diagnosed with PCa at recruitment and had not developed any other types of cancers during follow-up (last follow-up in January 2022). A PCa diagnosis was identified from national cancer registries and self-report records (International Classification of Diseases [ICD] 10: C61). PCa-related death ( i.e. , lethal PCa) information was identified from death registries. The Chinese PCa cohort was a retrospective case-only cohort of 235 PCa patients who had undergone whole-exome sequencing (WES) of","PeriodicalId":8483,"journal":{"name":"Asian Journal of Andrology","volume":"25 3","pages":"433-434"},"PeriodicalIF":2.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/63/38/AJA-25-433.PMC10226507.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9541169","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}
Hui-Yu Dong, Lei Ding, Tian-Ren Zhou, Tao Yan, Jie Li, Chao Liang
Most prostate cancers initially respond to androgen deprivation therapy (ADT). With the long-term application of ADT, localized prostate cancer will progress to castration-resistant prostate cancer (CRPC), metastatic CRPC (mCRPC), and neuroendocrine prostate cancer (NEPC), and the transcriptional network shifted. Forkhead box protein A1 (FOXA1) may play a key role in this process through multiple mechanisms. To better understand the role of FOXA1 in prostate cancer, we review the interplay among FOXA1-targeted genes, modulators of FOXA1, and FOXA1 with a particular emphasis on androgen receptor (AR) function. Furthermore, we discuss the distinct role of FOXA1 mutations in prostate cancer and clinical significance of FOXA1. We summarize possible regulation pathways of FOXA1 in different stages of prostate cancer. We focus on links between FOXA1 and AR, which may play different roles in various types of prostate cancer. Finally, we discuss FOXA1 mutation and its clinical significance in prostate cancer. FOXA1 regulates the development of prostate cancer through various pathways, and it could be a biomarker for mCRPC and NEPC. Future efforts need to focus on mechanisms underlying mutation of FOXA1 in advanced prostate cancer. We believe that FOXA1 would be a prognostic marker and therapeutic target in prostate cancer.
{"title":"FOXA1 in prostate cancer.","authors":"Hui-Yu Dong, Lei Ding, Tian-Ren Zhou, Tao Yan, Jie Li, Chao Liang","doi":"10.4103/aja202259","DOIUrl":"https://doi.org/10.4103/aja202259","url":null,"abstract":"<p><p>Most prostate cancers initially respond to androgen deprivation therapy (ADT). With the long-term application of ADT, localized prostate cancer will progress to castration-resistant prostate cancer (CRPC), metastatic CRPC (mCRPC), and neuroendocrine prostate cancer (NEPC), and the transcriptional network shifted. Forkhead box protein A1 (FOXA1) may play a key role in this process through multiple mechanisms. To better understand the role of FOXA1 in prostate cancer, we review the interplay among FOXA1-targeted genes, modulators of FOXA1, and FOXA1 with a particular emphasis on androgen receptor (AR) function. Furthermore, we discuss the distinct role of FOXA1 mutations in prostate cancer and clinical significance of FOXA1. We summarize possible regulation pathways of FOXA1 in different stages of prostate cancer. We focus on links between FOXA1 and AR, which may play different roles in various types of prostate cancer. Finally, we discuss FOXA1 mutation and its clinical significance in prostate cancer. FOXA1 regulates the development of prostate cancer through various pathways, and it could be a biomarker for mCRPC and NEPC. Future efforts need to focus on mechanisms underlying mutation of FOXA1 in advanced prostate cancer. We believe that FOXA1 would be a prognostic marker and therapeutic target in prostate cancer.</p>","PeriodicalId":8483,"journal":{"name":"Asian Journal of Andrology","volume":"25 3","pages":"287-295"},"PeriodicalIF":2.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/94/52/AJA-25-287.PMC10226509.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9534745","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}
Yuan-Bin Huang, Wei-Lin Li, Man Sun, Xu Duan, Yu-Tong Wang, Lu-Xin Zhang, Zi-Han Xin, Zhi-Fei Yun, Bo Fan, Xian-Cheng Li
Studies have investigated the effects of androgen deprivation therapy (ADT) use on the incidence and clinical outcomes of coronavirus disease 2019 (COVID-19); however, the results have been inconsistent. We searched the PubMed, Medline, Cochrane, Scopus, and Web of Science databases from inception to March 2022; 13 studies covering 84 003 prostate cancer (PCa) patients with or without ADT met the eligibility criteria and were included in the meta-analysis. We calculated the pooled risk ratios (RRs) with 95% confidence intervals (CIs) to explore the association between ADT use and the infection risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severity of COVID-19. After synthesizing the evidence, the pooled RR in the SARS-CoV-2 positive group was equal to 1.17, and the SARS-CoV-2 positive risk in PCa patients using ADT was not significantly different from that in those not using ADT (P = 0.544). Moreover, no significant results concerning the beneficial effect of ADT on the rate of intensive care unit admission (RR = 1.04, P = 0.872) or death risk (RR = 1.23, P = 0.53) were found. However, PCa patients with a history of ADT use had a markedly higher COVID-19 hospitalization rate (RR = 1.31, P = 0.015) than those with no history of ADT use. These findings indicate that ADT use by PCa patients is associated with a high risk of hospitalization during infection with SARS-CoV-2. A large number of high quality studies are needed to confirm these results.
研究探讨了雄激素剥夺疗法(ADT)对2019冠状病毒病(COVID-19)发病率和临床结局的影响;然而,结果却不一致。我们检索了PubMed、Medline、Cochrane、Scopus和Web of Science数据库,从成立到2022年3月;13项研究涵盖84003例伴有或未伴有ADT的前列腺癌(PCa)患者,符合入选标准,纳入meta分析。我们以95%置信区间(ci)计算合并风险比(rr),探讨ADT使用与严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)感染风险和COVID-19严重程度之间的关系。综合证据,SARS-CoV-2阳性组的合并RR = 1.17,使用ADT的PCa患者与未使用ADT的PCa患者的SARS-CoV-2阳性风险差异无统计学意义(P = 0.544)。此外,ADT对重症监护病房入院率(RR = 1.04, P = 0.872)和死亡风险(RR = 1.23, P = 0.53)的有益影响未见显著结果。然而,有ADT使用史的PCa患者的COVID-19住院率明显高于无ADT使用史的PCa患者(RR = 1.31, P = 0.015)。这些发现表明,PCa患者使用ADT与感染SARS-CoV-2期间住院的高风险相关。需要大量高质量的研究来证实这些结果。
{"title":"Impacts of androgen deprivation therapy on the risks and outcomes of SARS-CoV-2 infection in patients with prostate cancer.","authors":"Yuan-Bin Huang, Wei-Lin Li, Man Sun, Xu Duan, Yu-Tong Wang, Lu-Xin Zhang, Zi-Han Xin, Zhi-Fei Yun, Bo Fan, Xian-Cheng Li","doi":"10.4103/aja202246","DOIUrl":"https://doi.org/10.4103/aja202246","url":null,"abstract":"<p><p>Studies have investigated the effects of androgen deprivation therapy (ADT) use on the incidence and clinical outcomes of coronavirus disease 2019 (COVID-19); however, the results have been inconsistent. We searched the PubMed, Medline, Cochrane, Scopus, and Web of Science databases from inception to March 2022; 13 studies covering 84 003 prostate cancer (PCa) patients with or without ADT met the eligibility criteria and were included in the meta-analysis. We calculated the pooled risk ratios (RRs) with 95% confidence intervals (CIs) to explore the association between ADT use and the infection risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severity of COVID-19. After synthesizing the evidence, the pooled RR in the SARS-CoV-2 positive group was equal to 1.17, and the SARS-CoV-2 positive risk in PCa patients using ADT was not significantly different from that in those not using ADT (P = 0.544). Moreover, no significant results concerning the beneficial effect of ADT on the rate of intensive care unit admission (RR = 1.04, P = 0.872) or death risk (RR = 1.23, P = 0.53) were found. However, PCa patients with a history of ADT use had a markedly higher COVID-19 hospitalization rate (RR = 1.31, P = 0.015) than those with no history of ADT use. These findings indicate that ADT use by PCa patients is associated with a high risk of hospitalization during infection with SARS-CoV-2. A large number of high quality studies are needed to confirm these results.</p>","PeriodicalId":8483,"journal":{"name":"Asian Journal of Andrology","volume":"25 3","pages":"366-374"},"PeriodicalIF":2.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/80/ad/AJA-25-366.PMC10226495.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9541137","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}
Li Li, Min-Yan Wang, Hua-Bo Jiang, Chun-Rong Guo, Xian-Dan Zhu, Xia-Qin Yao, Wei-Wei Zeng, Yuan Zhao, Ling-Kan Chi
Bisphenol A is a common environmental factor and endocrine disruptor that exerts a negative impact on male reproductive ability. By exploring bisphenol A-induced testicular cell death using the Institute of Cancer Research (ICR) mouse model, we found that a ferroptosis phenomenon may exist. Mice were divided into six groups and administered different doses of bisphenol A via intragastric gavage once daily for 45 consecutive days. Serum was then collected to determine the levels of superoxide dismutase and malondialdehyde. Epididymal sperm was also collected for semen analysis, and testicular tissue was collected for ferritin content determination, electron microscope observation of mitochondrial morphology, immunohistochemistry, real-time quantitative polymerase chain reaction, and western blot analysis. Exposure to bisphenol A was found to decrease sperm quality and cause oxidative damage, iron accumulation, and mitochondrial damage in the testes of mice. In addition, bisphenol A was confirmed to affect the expression of the ferroptosis-related genes, glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), cyclooxygenase 2 (COX2), and acyl-CoA synthetase 4 (ACSL4) in mouse testicular tissues. Accordingly, we speculate that bisphenol A induces oxidative stress, which leads to the ferroptosis of testicular cells. Overall, the inhibition of ferroptosis may be a potential strategy to reduce male reproductive toxicity caused by bisphenol A.
{"title":"Bisphenol A induces testicular oxidative stress in mice leading to ferroptosis.","authors":"Li Li, Min-Yan Wang, Hua-Bo Jiang, Chun-Rong Guo, Xian-Dan Zhu, Xia-Qin Yao, Wei-Wei Zeng, Yuan Zhao, Ling-Kan Chi","doi":"10.4103/aja202266","DOIUrl":"https://doi.org/10.4103/aja202266","url":null,"abstract":"<p><p>Bisphenol A is a common environmental factor and endocrine disruptor that exerts a negative impact on male reproductive ability. By exploring bisphenol A-induced testicular cell death using the Institute of Cancer Research (ICR) mouse model, we found that a ferroptosis phenomenon may exist. Mice were divided into six groups and administered different doses of bisphenol A via intragastric gavage once daily for 45 consecutive days. Serum was then collected to determine the levels of superoxide dismutase and malondialdehyde. Epididymal sperm was also collected for semen analysis, and testicular tissue was collected for ferritin content determination, electron microscope observation of mitochondrial morphology, immunohistochemistry, real-time quantitative polymerase chain reaction, and western blot analysis. Exposure to bisphenol A was found to decrease sperm quality and cause oxidative damage, iron accumulation, and mitochondrial damage in the testes of mice. In addition, bisphenol A was confirmed to affect the expression of the ferroptosis-related genes, glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), cyclooxygenase 2 (COX2), and acyl-CoA synthetase 4 (ACSL4) in mouse testicular tissues. Accordingly, we speculate that bisphenol A induces oxidative stress, which leads to the ferroptosis of testicular cells. Overall, the inhibition of ferroptosis may be a potential strategy to reduce male reproductive toxicity caused by bisphenol A.</p>","PeriodicalId":8483,"journal":{"name":"Asian Journal of Andrology","volume":"25 3","pages":"375-381"},"PeriodicalIF":2.9,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/de/cd/AJA-25-375.PMC10226511.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9542423","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}