Andrology最新文献

{"title":"Kinetics of the inhibition and recovery of spermatogenesis induced by treatment with WIN 18,446, a male contraceptive, in mice.","authors":"Jisun Paik, Jessica M Snyder, Andy Kim, Michael Haenisch, Kevin Fogassy, John K Amory","doi":"10.1111/andr.13807","DOIUrl":"https://doi.org/10.1111/andr.13807","url":null,"abstract":"<p><strong>Background: </strong>Retinoic acid (RA) is essential for spermatogenesis. Genetic deletion of the retinoic acid synthesizing enzymes, Aldh1a1/1a2, in the testes causes infertility in mice. An inhibitor of the ALDH1A1/1A2 enzymes, WIN 18,446 reversibly inhibit spermatogenesis and is a promising approach to male contraception. Previously we reported that a 4-week treatment of WIN 18,446 inhibits spermatogenesis and 9-week recovery from treatment normalized fertility of treated mice. However, the precise kinetics of this process has not been studied.</p><p><strong>Objectives: </strong>To extend our knowledge of kinetics of ALDH1A inhibition, we studied the changes in the seminiferous epithelium and retinoic acid synthesis capacity of the testes during 4 weeks of WIN 18,446 treatment and during 9 weeks of recovery.</p><p><strong>Materials and methods: </strong>Male mice were fed a diet containing WIN 18,446 for 4 weeks followed by a normal diet for up to 8 weeks. Frequently, during the treatment and recovery period, five mice were euthanized, and testes were analyzed for testicular histology and retinoic acid synthesis capacity and compared with controls.</p><p><strong>Results: </strong>Testes weights progressively decreased, and the seminiferous epithelium deteriorated over the time with WIN 18,446 treatment and returned to normal after 8 weeks. Retinoic acid synthesis capacity was significantly inhibited 3 days after the WIN 18,446 treatment and recovered after 7 days of no treatment. After 4 weeks of treatment, complete blockage of spermatogenesis with only spermatogonia and Sertoli cells was observed. The RA biosynthetic capacity of the testes was significantly reduced before the disruption of spermatogenesis was observed and recovered prior to the reinitiation of spermatogonial differentiation.</p><p><strong>Conclusions: </strong>Effects of ALDH1A inhibition on spermatogenesis are reversible. Our observation that strong inhibition of ALDH1A disrupts the seminiferous epithelium prior to the completion of a full cycle of spermatogenesis suggests that episodic inhibition of ALDH1A may function as a male contraceptive.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674936","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":"Surgical treatment of hypospadias with lichen sclerosus: Long-term outcomes from a single center.","authors":"Bo Yang, Xue-Jun Wang, Li Bo-Ya, Shao-Ji Chen, Jiao Li, Yan-Mei Deng, Li-Shuang Bai, Lin-Hong Song, Dao-Rui Qin, Yu Mao, Yun-Man Tang","doi":"10.1111/andr.13805","DOIUrl":"https://doi.org/10.1111/andr.13805","url":null,"abstract":"<p><strong>Background: </strong>Hypospadias with lichen sclerosus (LS) poses surgical challenges due to lack of materials for urethral reconstruction and coverage and the limited number of reports on this clinical condition.</p><p><strong>Objectives: </strong>To report surgical strategies and outcomes for primary and redo hypospadias patients with LS.</p><p><strong>Materials and methods: </strong>We conducted a retrospective observational descriptive study with 31 patients with primary/redo hypospadias and LS between 2013 and 2023. Of these patients, 9 had primary hypospadias with 7 distal types and 2 proximal types, and 22 were redo patients. Nineteen of the 31 patients underwent various surgical techniques, and 12 underwent the oral mucosa onlay procedure (OMOP). Postoperative uroflowmetry, hypospadias objective scoring evaluation (HOSE), and complications were evaluated.</p><p><strong>Results: </strong>For primary distal hypospadias with LS-affected skin, five patients underwent circumcision; these patients had normal postoperative urinary flow, and only one patient had an inconspicuous penis after surgery. For the patients with primary proximal hypospadias with an LS-affected urethra, one patient required perineal urethrostomy following a modified Koyanagi procedure for recurrent stricture; the other patient underwent two-stage transverse preputial island flap urethroplasty with no postoperative lower urinary tract symptoms (LUTS) and satisfactory aesthetic scores. In two remaining cases of primary distal hypospadias with meatus/urethral LS, no LUTS or postoperative complications occurred following meatoplasty/circumcision and penile basal fixation. During reoperations, compared with those of patients who underwent other redo procedures, twelve patients who underwent OMOP had better Qmax and uroflowmetry (p = 0.002) and higher HOSE scores (p = 0.01).</p><p><strong>Conclusions: </strong>For primary hypospadias patients with LS, enhanced exposure of the penile shaft and glans may benefit distal hypospadias, whereas staged surgery may be suitable for proximal hypospadias. The oral mucosa is favored for urethral augmentation in patients with redo hypospadias complicated with LS, and the OMOP can address neourethra coverage effectively.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646791","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":"Successful colonization of the testicular germinal epithelium by bone marrow stem cells producing spermatozoa of donor genotype is rare.","authors":"Nandini Shankara-Narayana, Bing Yu, Jie Qian, Steven Allen, Brisa Reyes, Anthony Cheong, Joseph Daniele, Sue Sleiman, Fey Bacha, Veena Jayadev, David J Handelsman","doi":"10.1111/andr.13799","DOIUrl":"https://doi.org/10.1111/andr.13799","url":null,"abstract":"<p><strong>Background: </strong>It is not known whether bone marrow stem cells when injected intravenously for a bone marrow transplant colonize the human testicular epithelium. No previous studies of sperm genotype after bone marrow transplantation are reported.</p><p><strong>Objectives: </strong>To differentiate host from donor genotype in spermatozoa of men who have undergone successful bone marrow transplants.</p><p><strong>Materials and methods: </strong>Triplet DNA samples (spermatozoa, blood, and hair) obtained from men who had recovered sperm production after bone marrow transplant were genotyped using 44 autosomal and three sex-related single nucleotide polymorphisms to determine the tissue genotype in pairwise comparisons of DNA profiles.</p><p><strong>Results: </strong>Participants were 14 men at a median of 5.5 years after allogeneic bone marrow transplant who had a median sperm output of 77 million spermatozoa/ejaculate. In 14/14 the donor (leukocyte) DNA genotype differed significantly from the spermatozoa and hair genotypes whereas hair and sperm genotypes showed no variations.</p><p><strong>Discussion: </strong>These data suggest that paternity after a successful bone marrow transplant is likely to be of the host and not the donor's genetic origins. The study's small sample size reflects the paucity of eligible man with recovered spermatogenesis after bone marrow transplant and represents preliminary evidence. A large-scale epidemiological analysis to estimate the frequency of bone marrow donor stem cell colonization of the testicular germinal epithelium based on progeny sex ratio and frequency of female donors is proposed.</p><p><strong>Conclusion: </strong>Successful colonization of the testicular germinal and hair follicle epithelia by allogeneic bone marrow transplant donor stem cells is rare or does not occur.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646790","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":"EP300-interacting inhibitor of differentiation 3 is required for spermatogenesis in mice.","authors":"Ping Zhang, Longsheng Zhang, Li Yu, Xinli Zhou, Xu Chen, Yuchuan Zhou, Ningling Wang, Hui Zhu","doi":"10.1111/andr.13800","DOIUrl":"https://doi.org/10.1111/andr.13800","url":null,"abstract":"<p><strong>Background: </strong>Mammalian spermatogenesis is a highly complex process of cell proliferation, meiosis, and differentiation. A series of genes are expressed in an orderly and precise manner to ensure spermatogenesis, with chromatin undergoing intricate changes throughout. EP300-interacting inhibitor of differentiation 3 (Eid3) is a testis-enriched gene, but its role in male reproduction remains unclear.</p><p><strong>Objective: </strong>To investigate the role of EID3 in male spermatogenesis and explore the potential underlying mechanism.</p><p><strong>Materials and methods: </strong>We generated Eid3 knockout mouse model using the CRISPR-Cas9 system. We measured the expression of EID3 in mouse tissues and testicular cell populations by qRT-PCR and western blot. Histological analysis, including hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining, together with computer-assisted sperm analysis (CASA), were performed to evaluate the effect of EID3 on spermatogenesis in mice. Light and ultrastructural microscopy were used to evaluate the morphology and structure of the Eid3^-/- spermatozoa. We used western blot and immunofluorescence to further analyze the function of EID3 in spermiogenesis.</p><p><strong>Results: </strong>Eid3^-/- mouse showed a significant decrease in sperm count, motility, and morphology. Loss of EID3 impaired the normal meiotic process and induced apoptosis of abnormally developing spermatocytes, ultimately resulting in the decrease of sperm cell number. Additionally, EID3 deficiency led to a decrease in histone acetylation levels in spermatids, impaired histone-to-protamine transition and chromatin condensation process, and ultimately resulted in abnormal sperm morphology.</p><p><strong>Discussion and conclusions: </strong>This study confirms for the first time that EID3 is crucial for meiosis and chromatin condensation during spermatogenesis, and EID3 deficiency leads to a significant decrease in sperm parameters. Given the high expression paradigm of Eid3 in human testis, EID3 likely plays a role in human reproduction. Future research could provide a new target for the clinical diagnosis and treatment of male infertility.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646789","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":"Associations of vasectomy with sexual dysfunctions and the sex life of middle-aged men.","authors":"Matthias Jahnen, Anna Rechberger, Valentin H Meissner, Stefan Schiele, Helga Schulwitz, Jürgen E Gschwend, Kathleen Herkommer","doi":"10.1111/andr.13804","DOIUrl":"https://doi.org/10.1111/andr.13804","url":null,"abstract":"<p><strong>Background: </strong>Vasectomy is a safe and effective form of contraception. However, fear of altered sexual function is still associated with vasectomy in many men.</p><p><strong>Objectives: </strong>To assess the prevalence of vasectomy among middle-aged men in Germany and to investigate possible associations between a previous vasectomy and sexual dysfunctions.</p><p><strong>Methods: </strong>Data on lifestyle, sexual activity, satisfaction, and dysfunction from 5425 middle-aged, heterosexual men were collected. Differences between vasectomized (VM) and non-vasectomized men (NVM) were assessed. Multiple logistic regression analyses were calculated to determine variables associated with erectile dysfunction (ED), premature ejaculation (PE), and low libido.</p><p><strong>Results: </strong>5425 men with a mean age of 50.6 ± 0.8 years were included in this analysis. Vasectomy was performed in 12.5% (679/5425) on average 8.6 ± 5.8 years ago. 84.4% were sexually active in the last 3 months (93.0% in vasectomized men vs. 83.2% in non-vasectomized men; p < 0.001), and 45.4% were satisfied with their sexual life (55.2% in vasectomized men vs. 44.0% in non-vasectomized men; p < 0.001). The prevalence of erectile dysfunction was significantly lower in vasectomized men (12.1% vs. 20.1%; p < 0.001), and a previous vasectomy was associated with a decreased risk for erectile dysfunction in multivariable regression analysis (OR: 0.65 [0.40-0.83]). The prevalence of low libido (4.7% in vasectomized men vs. 7.1% in non-vasectomized men; p = 0.02) was marginally higher among non-vasectomized men. The prevalence of premature ejaculation (7.1% in vasectomized men vs. 6.1% in non-vasectomized men, p = 0.5) did not differ significantly between vasectomized and non-vasectomized men.</p><p><strong>Discussion: </strong>A previous vasectomy is not associated with an increased risk for sexual dysfunction, and vasectomized middle-aged men are more sexually active and satisfied compared to their non-vasectomized counterparts. The main limitations are the retrospective design and missing pre-vasectomy data.</p><p><strong>Conclusions: </strong>Men can be reassured that the fear of sexual dysfunctions and diminished sex life after a vasectomy is unwarranted.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of intra-individual variation in the detection of thresholds for DFI and for misclassification rates: A retrospective analysis of 14,775 SCSA^® tests.","authors":"Preben Christensen, Robert Fischer, Wolfgang Schulze, Vera Baukloh, Kimberly Kienast, Graham Coull, Erik T Parner","doi":"10.1111/andr.13801","DOIUrl":"https://doi.org/10.1111/andr.13801","url":null,"abstract":"<p><strong>Background: </strong>Sperm DNA damage is associated with reduced male fertility after natural conception and intrauterine insemination. However, the impact on in vitro fertilization (IVF) and especially intracytoplasmic sperm injection (ICSI) treatments is still unclear. Few studies have focused on the intra-individual variation in DFI even though it may have an important role to play in terms of detection of thresholds and for misclassification rates.</p><p><strong>Methods: </strong>Results for Sperm Chromatin Structure Assay (SCSA^®) tests performed for 70 European fertility clinics between January 1^st, 2008 and December 31^st, 2022 were examined. A small retrospective study included 406 couples receiving their first treatment with IVF or ICSI. These results were then used for a mathematical simulation to investigate the role of intra-individual variation. The large retrospective study included a total of 14,138 diagnostic tests and 637 tests from an IUI study. The distribution of DFI was assessed for the IUI cohort and cohorts of patients attending Sims IVF and Fertility Center Hamburg (FCH). Descriptive analysis of the data was performed regarding time of year, male age, and year.</p><p><strong>Results: </strong>When DFI was above the thresholds of 15 and 25, a significant reduction in ongoing pregnancies after 12 weeks of gestation was observed for IVF and ICSI treatments, respectively. For IVF treatments, the pregnancy rate was reduced from 45.1% to 24.6%, odds ratio = 2.58 (p = 0.004). For ICSI treatments, the pregnancy rate was reduced from 48.6% to 29.6%, odds ratio = 2.00 (p = 0.032). Intra-individual variation was significantly related to the misclassification rate and the sample size required to identify a threshold. The percentage of patients with a DFI below 15 was 64.8% for the IUI cohort and 51.7% and 41.6% for cohorts of patients attending Sims IVF and FCH, respectively. The median DFI for these cohorts differed significantly and was 11.6, 15.0 and 17.2, respectively. DFI shows a seasonal variation, and increases with male age. During the past 15 years, the median DFI has increased by 0.05% per year (p = 0.02).</p><p><strong>Discussion and conclusions: </strong>Ongoing pregnancy rates are reduced significantly for both IVF and ICSI treatments when DFI is above the thresholds of 15 and 25, respectively. The misclassification rate and the required sample size increase with increasing intra-individual variation. Couples with a DFI above 15 are more likely to experience failed assisted reproductive technology (ART) cycles. DFI appears to have increased during the past 15 years.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638565","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":"European Academy of Andrology (EAA): Report of activities in 2023.","authors":"Ewa Rajpert-De Meyts, Hermann M Behre","doi":"10.1111/andr.13794","DOIUrl":"https://doi.org/10.1111/andr.13794","url":null,"abstract":"","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association of men's beverage intake with semen quality and assisted reproduction outcomes in patients undergoing fertility treatment.","authors":"Albert Salas-Huetos, Makiko Mitsunami, Lidia Mínguez-Alarcón, Eduardo Ortiz-Panozo, Michelle M Murphy, Irene Souter, Jorge E Chavarro","doi":"10.1111/andr.13795","DOIUrl":"https://doi.org/10.1111/andr.13795","url":null,"abstract":"<p><strong>Background: </strong>Although some studies have investigated the relationships between beverage intake and reproductive health these have generated conflicting results.</p><p><strong>Objectives: </strong>To evaluate the associations between men's beverage intake and semen quality parameters and couple outcomes of medically assisted reproduction.</p><p><strong>Material and methods: </strong>The relationship between preconception beverage intake and semen quality was evaluated in 896 semen samples from 343 men. The relation between beverage intake and medically assisted reproduction outcomes (fertilization, implantation, clinical pregnancy, total/clinical pregnancy loss, and live birth) was evaluated in 296 men and their female partners who underwent 714 medically assisted reproduction cycles: 306 intrauterine insemination cycles and 408 in vitro fertilization. Intake of caffeinated, alcoholic, sugar-sweetened, and artificially sweetened beverages and sub-groups were considered as exposures.</p><p><strong>Results: </strong>Caffeinated, alcoholic, sugar-sweetened, and artificially sweetened beverage intake was not associated with semen quality parameters or with fertilization, implantation, clinical pregnancy, or live birth in couples undergoing medically assisted reproduction. When specific types of beverages were explored, there was an inverse association between a greater intake of coffee/tea with caffeine and lower live birth probabilities in couples undergoing in vitro fertilization cycles. The adjusted probabilities (95% confidence interval) of live birth in the lowest and highest tertiles of intake were 0.49 (0.38, 0.61) and 0.33 (0.24, 0.43) for coffee with caffeine, and 0.49 (0.33, 0.51) and 0.31 (0.22, 0.41) for tea with caffeine. A similar trend was detected with liquor intake and live birth probabilities: 0.45 (0.37, 0.53) and 0.32 (0.25, 0.41). We also found an association between a greater beer intake and higher live birth probabilities. The adjusted probabilities (95% confidence interval) in the lowest and highest quartile of intake were 0.32 (0.23, 0.42) and 0.51 (0.39, 0.62).</p><p><strong>Conclusion: </strong>Male preconception intakes of coffee, tea, and liquor were inversely associated, whereas beer intake was positively associated with the probability of live birth during infertility treatment.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The aporetic dialogues of Modena on gender differences: Is it all about testosterone? EPISODE I: CRIME.","authors":"Giulia Brigante, Giulia D'Angelo, Vanessa Caccin, Silvia Coluccia, Immacolata Conte, Veronica Maria Demichelis, Rossana Cecchi, Manuela Simoni","doi":"10.1111/andr.13797","DOIUrl":"https://doi.org/10.1111/andr.13797","url":null,"abstract":"<p><p>This is the first episode of a series of four discussions on the differences between males and females, in apparently non-andrological fields. You will read the transcript of discussions that actually took place at the Endocrinology Unit in Modena, Italy, in the form of the aporetic dialogues of ancient Greece. In this episode, the role of testosterone in gender differences in criminal behavior will be explored. The discussants were divided into two groups: group 1, which supports the thesis of a predominant role of testosterone, and group 2, which opposes it. The first group affirmed that both endogenous testosterone and anabolic-androgenic steroids could trigger aggressive and criminal behavior, regardless of predisposition to psychiatric disease or sociocultural background. The second group asserted the multifactorial genesis of aggressive and criminal behavior, citing other hormonal and non-hormonal factors, such as neurotransmitters, cortisol, and sociological and psychological aspects. In the end, a forensic physician, acting as a referee, tried to resolve the aporia: are the two theories equivalent or one is superior?</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602282","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":"Dexamethasone is a regulator of clock genes in testicular peritubular cells.","authors":"Harald Welter, Nicole Kreitmair, Michaela Schneider, Julia Schneider, Stoyan Petkov, Youli Stepanov, Frank-Michael Köhn, Ulrich Pickl, Matthias Trottmann, Thomas Fröhlich, Rüdiger Behr, Artur Mayerhofer","doi":"10.1111/andr.13788","DOIUrl":"10.1111/andr.13788","url":null,"abstract":"<p><strong>Background: </strong>We recently found that peritubular cells of the human testis are a dominant site of expression of the glucocorticoid receptor (GR; encoded by NR3C1). Activation of GR by dexamethasone (Dex) strongly influences the phenotype of cultured human testicular peritubular cells (HTPCs), causing massive changes of their proteome and secretome. As glucocorticoids (GC) are also known to set the internal clock of peripheral organs by regulating clock genes, we tested such an influence of Dex in HTPCs.</p><p><strong>Methods: </strong>We performed cellular studies with HTPCs and immortalized nonhuman primate (Callithrix jacchus; Cj)-derived peritubular cells, organotypic incubations of testicular fragments of Cj, qPCR and proteomic, as well as immunohistochemical studies.</p><p><strong>Results: </strong>Basal clock gene expression levels, when monitored by qPCR under standard culture conditions, showed alterations over 24 h, suggesting an endogenous circadian rhythm, especially for BMAL1. Dex (1 µM) when added to cells, caused a strong and significant increase of PER1, followed by elevations of BMAL1, and other clock genes. This action was observed as early as 4 h after the addition of Dex. Immunohistochemistry and data mining revealed GR in testicular peritubular cells and other somatic cells of Cj, in situ. We therefore performed organotypic incubations of testicular fragments of Cj (n = 3) and found that upon addition of Dex (1 µM), mRNA levels of BMAL1 and PER1 also increased in samples of two out of three animals after 6 h. Mass spectrometry did, however, not reveal significant alterations of the testicular proteome, possibly due to the short time point and/or the fact that the somatic GR-expressing cells represent only a small portion of the testis. In support for this assumption, Dex (1 µM; 6 h) significantly increased mRNA levels of BMAL1 and PER1 in Cj-derived immortalized testicular peritubular cells.</p><p><strong>Conclusion: </strong>The results indicate that an internal clock system likely exists in peritubular cells of the testis and that Dex, via testicular GR expressed by peritubular cells and other somatic cells, is a strong regulator of this system. In a physiological situation, GC thus may be important regulators of the testicular clock, while in a situation of prolonged stress or GC-medication, derangements in clock gene expression may result.</p>","PeriodicalId":7898,"journal":{"name":"Andrology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590091","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}