Basic and Clinical Andrology最新文献

{"title":"Is BRD7 associated with spermatogenesis impairment and male infertility in humans? A case-control study in a Han Chinese population.","authors":"Tianrong He,&nbsp;Mohan Liu,&nbsp;Dachang Tao,&nbsp;Xiangyou Leng,&nbsp;Zhaokun Wang,&nbsp;Shengyu Xie,&nbsp;Yangwei Zhang,&nbsp;Xinyue Zhang,&nbsp;Xiaolan Tan,&nbsp;Yunqiang Liu,&nbsp;Yuan Yang","doi":"10.1186/s12610-021-00139-3","DOIUrl":"https://doi.org/10.1186/s12610-021-00139-3","url":null,"abstract":"<p><strong>Background: </strong>Bromodomain-containing protein 7 (BRD7), a member of the bromodomain-containing protein family, plays important roles in chromatin modification and transcriptional regulation. A recent model of Brd7-knockout mice presented azoospermia and male infertility, implying the potential role of BRD7 in spermatogenic failure in humans. This case-control study aimed to explore the association of the BRD7 gene with spermatogenic efficiency and the risk of spermatogenic defects in humans.</p><p><strong>Results: </strong>A total of six heterozygous variants were detected in the coding and splicing regions of the BRD7 gene in patients with azoospermia. For each of four rare variants predicted to potentially damage BRD7 function, we further identified these four variants in oligozoospermia and normozoospermia as well. However, no difference in the allele and genotype frequencies of rare variants were observed between cases with spermatogenic failure and controls with normozoospermia; the sperm products of variant carriers were similar to those of noncarriers. Moreover, similar distribution of the alleles, genotypes and haplotypes of seven tag single nucleotide polymorphisms (tagSNPs) was observed between the cases with azoospermia and oligozoospermia and controls with normozoospermia; associations of tagSNP-distinguished BRD7 alleles with sperm products were not identified.</p><p><strong>Conclusions: </strong>The lack of an association of BRD7-linked rare and common variants with spermatogenic failure implied a limited contribution of the BRD7 gene to spermatogenic efficiency and susceptibility to male infertility in humans.</p>","PeriodicalId":8730,"journal":{"name":"Basic and Clinical Andrology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2021-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39376578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Will whole-genome sequencing become the first-line genetic analysis for male infertility in the near future?","authors":"Farah Ghieh,&nbsp;Anne-Laure Barbotin,&nbsp;Clara Leroy,&nbsp;François Marcelli,&nbsp;Nelly Swierkowsky-Blanchard,&nbsp;Valérie Serazin,&nbsp;Béatrice Mandon-Pepin,&nbsp;François Vialard","doi":"10.1186/s12610-021-00138-4","DOIUrl":"https://doi.org/10.1186/s12610-021-00138-4","url":null,"abstract":"<p><p>Whereas the initially strategy for the genetic analysis of male infertility was based on a candidate gene approach, the development of next-generation sequencing technologies (such as whole-exome sequencing (WES)) provides an opportunity to analyze many genes in a single procedure. In order to recommend WES or whole-genome sequencing (WGS) after genetic counselling, an objective evaluation of the current genetic screening strategy for male infertility is required, even if, at present, we have to take into consideration the complexity of such a procedure, not discussed in this commentary.</p>","PeriodicalId":8730,"journal":{"name":"Basic and Clinical Andrology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2021-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39335543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of vitamin D supplementation in extender on sperm kinematics and apoptosis following the freeze-thaw process in normozoospermic and asthenozoospermic Holstein bulls.","authors":"Reza Asadpour,&nbsp;Morteza Taravat,&nbsp;Maryam Rahbar,&nbsp;Mohammadrasoul Khoshniyat,&nbsp;Gholamreza Hamidian","doi":"10.1186/s12610-021-00137-5","DOIUrl":"https://doi.org/10.1186/s12610-021-00137-5","url":null,"abstract":"<p><strong>Background: </strong>Asthenozoospermia is a usual male infertility factor, characterized by decreased semen quality. It has been revealed that antioxidants improve sperm function, enhance endogenous antioxidant activities, and protect spermatozoa against oxidative damage during cryopreservation. This aimed to evaluate the effects of vitamin D on sperm kinematics and apoptosis in the semen of bulls with normozoospermia and asthenozoospermia after the freeze-thaw process. For this purpose, 32 semen samples of four Holstein bulls (normozoospermic, progressive motility > 70 %) and 32 semen samples of four bull (asthenozoospermic progressive motility < 40 %) were collected and pooled separately (normozoospermic and asthenozoospermic). Samples were then diluted into four equal aliquots of extender containing different vitamin D concentrations (0, 5, 10, and 50 ng/mL) and aspirated into a 0.5 mL straw.</p><p><strong>Results: </strong>The percentages of sperm progressive motility and viability were significantly higher (P < 0.05) in 50 ng/mL of vitamin D in normozoospermic group. Sperm kinematics parameters including curvilinear velocity (VCL), straight-line velocity (VSL), and average path velocity (VAP) were significantly higher in the high dose (50 ng/mL) vitamin D-treated group compared to the low dose vitamin D-treated group (5ng/mL) in normozoospermic bull semen samples. The supplementation of the semen extender with different concentrations of vitamin D could not increase the rate of acrosome integrity in normozoospermic bulls compared to the control group (P < 0.05). In the asthenozoospermic group, 10 ng/mL vitamin D-treated group could increase the rate of plasma membrane integrity compared to 5 ng/mL vitamin D-treated group (P < 0.05). The percentages of early-apoptosis (P = 0.049) and late-apoptosis (P = 0.005) were significantly higher in the asthenozoospermic than the normozoospermic group.</p><p><strong>Conclusions: </strong>The present study revealed that a high dose (50 ng/mL) of vitamin D protected normozoospermic bulls' sperms from the freezing procedure and lead to higher quality of frozen-thawed bull sperm.</p>","PeriodicalId":8730,"journal":{"name":"Basic and Clinical Andrology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2021-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8340513/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39275646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphometric analysis and redox state of the testicles in nandrolone decanoate and swimming treated adult male rats.","authors":"Jasmina Sretenovic,&nbsp;Jovana Joksimovic Jovic,&nbsp;Ivan Srejovic,&nbsp;Vladimir Zivkovic,&nbsp;Katarina Mihajlovic,&nbsp;Milica Labudovic-Borovic,&nbsp;Svetlana Trifunovic,&nbsp;Verica Milosevic,&nbsp;Dejan Lazic,&nbsp;Sergey Bolevich,&nbsp;Vladimir Jakovljevic,&nbsp;Zoran Milosavljevic","doi":"10.1186/s12610-021-00134-8","DOIUrl":"https://doi.org/10.1186/s12610-021-00134-8","url":null,"abstract":"<p><strong>Background: </strong>During the last decades, the abuse of anabolic androgenic steroids (AASs) has become popular among professional and recreational athletes. The abuse of AASs leads to decreased levels of sex hormones, but the available literature a gives very small pool of data regarding the effects of swimming alone or combined with AASs on testicle tissue. The aim of this study was to investigate the effects of four-week administration of nandrolone decanoate and swimming training alone or in combination on morphometric parameters, androgen receptor (AR) and redox state in testicle tissue. The study included Wistar albino male rats, 10 weeks old, classified into 4 groups: control (T-N-), nandrolone (T-N+), swimming training (T+N-) and swimming training with nandrolone (T+N+). The rats from nandrolone (N+) groups received nandrolone decanoate 20 mg/kg b.w.once per week. The rats from training (T+) groups, swam 1 h/day 5 days/week. The isolated testicles were measured, left testicles were routinely processed for histological analysis, while right testicles were homogenized and prepared for the analysis of the following oxidative stress biomarkers: index of lipid peroxidation (TBARS), nitrites, catalase, superoxide dismutase (SOD), and reduced glutathione (GSH).</p><p><strong>Results: </strong>Diameter, as well as cross-section area of seminiferous tubules were decreased by 10 % and 21 % (respectively) in the T-N+ group and by 15% and 41 % (respectively) in the T+N+ group compared to control. Interstitium of the testicles was decreased in all experimental groups. Reduction of immunoreactivity of AR in T-N+ group was 22 %, in T+N+ group was 9 % compared to control. TBARS levels were increased in T+N- and T+N+ groups. Nitrites were decreased in T+N+ group. Catalase activity was increased in all experimental groups. Swimming alone or combined with nandrolone decreased the level of GSH compared to control. SOD activity was decreased in T-N+ and T+N+ groups compared to control.</p><p><strong>Conclusions: </strong>Nandrolone alone or combined with swimming decreased morphometric parameters and amount of AR in testicle tissue. Changes in the redox state indicate reproductive dysfunction.</p>","PeriodicalId":8730,"journal":{"name":"Basic and Clinical Andrology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2021-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12610-021-00134-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39183656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viral infections that alter estrogen levels during pregnancy may contribute to the etiology of cryptorchidism.","authors":"Faruk Hadziselimovic","doi":"10.1186/s12610-021-00135-7","DOIUrl":"https://doi.org/10.1186/s12610-021-00135-7","url":null,"abstract":"<p><p>Cryptorchidism is as common as type 2 diabetes or celiac disease. Boys with congenital cryptorchidism are at increased risk of infertility and testicular cancer. Zika syndrome, which affects pregnant women, is associated with a high incidence of undescended testes in the infant, accompanied by epididymal anomalies. Zika and influenza virus infections during pregnancy trigger a strong anti-inflammatory immune response and elevated estradiol levels. Elevated estradiol and α-fetoprotein in syncytiotrophoblasts from women who have given birth to cryptorchid boys are indicative of increased estradiol levels in the fetus. Here, I present a hypothesis that hypogonadotropic hypogonadism, cryptorchidism, and retarded epididymal development may be due to elevated fetal estradiol levels caused by viral infection during pregnancy.</p>","PeriodicalId":8730,"journal":{"name":"Basic and Clinical Andrology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2021-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12610-021-00135-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39161564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Are serum levels of 25-hydroxy vitamin D reduced following orchiectomy in testicular cancer patients?","authors":"Klaus-Peter Dieckmann,&nbsp;Osama Andura,&nbsp;Uwe Pichlmeier,&nbsp;Klaus Martin Otte,&nbsp;Hendrik Isbarn,&nbsp;Christian Wülfing","doi":"10.1186/s12610-021-00136-6","DOIUrl":"https://doi.org/10.1186/s12610-021-00136-6","url":null,"abstract":"","PeriodicalId":8730,"journal":{"name":"Basic and Clinical Andrology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2021-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12610-021-00136-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39137696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contribution of serum anti-Müllerian hormone in the management of azoospermia and the prediction of testicular sperm retrieval outcomes: a study of 155 adult men.","authors":"Hamza Benderradji, Julie Prasivoravong, François Marcelli, Anne-Laure Barbotin, Sophie Catteau-Jonard, Carole Marchetti, Catherine Guittard, Philippe Puech, Valérie Mitchell, Jean-Marc Rigot, Arnauld Villers, Pascal Pigny, Clara Leroy","doi":"10.1186/s12610-021-00133-9","DOIUrl":"10.1186/s12610-021-00133-9","url":null,"abstract":"<p><strong>Background: </strong>Testicular sperm extraction (TESE) is the method of choice for recovering spermatozoa in patients with azoospermia. However, the lack of reliable biomarkers makes it impossible to predict sperm retrieval outcomes at TESE. To date, little attention has been given to anti-Müllerian hormone (AMH) serum levels in adult men with altered spermatogenesis. In this study we aimed to investigate whether serum concentrations of AMH and the AMH to total testosterone ratio (AMH/T) might be predictive factors for sperm retrieval outcomes during TESE in a cohort of 155 adult Caucasian men with azoospermia.</p><p><strong>Results: </strong>AMH serum levels were significantly lower in nonobstructive azoospermia (NOA) that was unexplained, cryptorchidism-related, cytotoxic and genetic (medians [pmol/l] = 30.1; 21.8; 26.7; 7.3; and p = 0.02; 0.001; 0.04; <0.0001, respectively]) compared with obstructive azoospermia (OA) (median = 44.8 pmol/l). Lowest values were observed in cases of genetic NOA (p < 0.0001, compared with unexplained NOA) and especially in individuals with non-mosaic Klinefelter syndrome (median = 2.3 pmol/l, p <0.0001). Medians of AMH/T values were significantly lower in genetic NOA compared to unexplained, cryptorchidism-related NOA as well as OA. Only serum concentrations of AMH differed significantly between positive and negative groups in men with non-mosaic Klinefelter syndrome. The optimal cut-off of serum AMH was set at 2.5 pmol/l. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of this cut-off to predict negative outcomes of SR were 100 %, 76.9 %, 66.6 %, 100 and 84.2 %, respectively.</p><p><strong>Conclusions: </strong>Serum AMH levels, but not AMH/T values, are a good marker for Sertoli and germ cell population dysfunction in adult Caucasian men with non-mosaic Klinefelter syndrome and could help us to predict negative outcomes of SR at TESE with 100 % sensitivity when serum levels of AMH are below 2.5 pmol/l.</p>","PeriodicalId":8730,"journal":{"name":"Basic and Clinical Andrology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2021-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39237334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revised manuscript R2, clean version are serum levels of 25-hydroxy vitamin D reduced following orchiectomy in testicular cancer patients?","authors":"Klaus-Peter Dieckmann,&nbsp;Osama Andura,&nbsp;Uwe Pichlmeier,&nbsp;Klaus Martin Otte,&nbsp;Hendrik Isbarn,&nbsp;Christian Wülfing","doi":"10.1186/s12610-021-00132-w","DOIUrl":"https://doi.org/10.1186/s12610-021-00132-w","url":null,"abstract":"<p><strong>Background: </strong>The testis represents one place where the progenitor of vitamin D is converted into its active form. Loss of one testis was suggested to result in reduced vitamin D serum levels. Vitamin D deficiency would represent a significant health problem in the long-term course of patients with testicular germ cell tumors (GCTs) since most of them survive. The purpose of this study was to look to the serum 25(OH)-Vitamin D (25OHD) levels in patients with GCTs before and after orchiectomy. A total of 177 GCT patients underwent measurements of serum 25OHD levels, thereof 83 with preoperative measurements and 94 with measurements at six particular time-points from immediate postoperatively to >24 months. Longitudinal assessments of 25OHD serum levels were performed in individual patients with repeated measurements. A second analysis involved patient cohorts with measurements at six postoperative time-points. Serum levels of patients were also compared with 2 control groups, one consisting of 84 patients with non-neoplastic testicular diseases and another with 237 patients with non-neoplastic urologic diseases. We also looked to associations of 25OHD levels with levels of testosterone, follicle stimulating hormone (FSH), age, histology of GCT and season. Descriptive statistical methods were employed to compare groups and to analyze changes over time.</p><p><strong>Results: </strong>Normal serum levels of 25OHD were found in 21.7%, 23.1%, 20.2%, 21.9% in GCT patients preoperatively, after >2 years, in control group 1 and control group 2, respectively. Levels were significantly higher in spring and summer, but no association was found with other parameters. We found a significant transient decrease of 25OHD levels with a nadir at 6-12 months after orchiectomy and a recovery thereafter.</p><p><strong>Conclusion: </strong>Contrasting with previous studies we found no permanent reduction of serum 25OHD levels after orchiectomy but transient postoperative drop of 25OHD levels. There were no associations of 25OHD levels with age, and levels of testosterone or FSH. Our results may point to a particular role of the testis in vitamin D metabolism and may thus enhance the understanding of the diverse physiological roles of the testis.</p>","PeriodicalId":8730,"journal":{"name":"Basic and Clinical Andrology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2021-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12610-021-00132-w","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39079202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"D-chiro-inositol, an aromatase down-modulator, increases androgens and reduces estrogens in male volunteers: a pilot study.","authors":"Giovanni Monastra, Mónica Vazquez-Levin, Maria Salome Bezerra Espinola, Gabriele Bilotta, Antonio Simone Laganà, Vittorio Unfer","doi":"10.1186/s12610-021-00131-x","DOIUrl":"10.1186/s12610-021-00131-x","url":null,"abstract":"<p><strong>Background: </strong>Androgen deficiency affects men in the adulthood, causing several harmful effects at the reproductive and behavioural levels. Since aromatase is an enzyme that catalyses the conversion of androgens to estrogens, and it is responsible for an adequate balance of both sex hormones in males and females, the administration of molecules acting as down modulators may contribute to restore an abnormal enzymatic activity. A prospective pilot study was carried out to investigate the effect of D-chiro-inositol, a putative aromatase down-modulator, on serum levels of testosterone, estradiol, estrone, dehydroepiandrosterone and epiandrosterone from a group of adult male volunteers. Glucose, insulin, follicle-stimulating hormone, luteinizing hormone, inhibin B, D-chiro-inositol and myo-inositol serum levels were also measured.</p><p><strong>Results: </strong>Male volunteers were selected according to age and body mass index. Subjects with altered glycemia and/or hormonal status, due to advanced age or abnormal weight, were enrolled in the study. Each of the 10 volunteers enrolled took oral D-chiro-inositol (1 g/day) for 1 month. Serum assays of selected markers were performed at baseline (control) and after treatment. D-chiro-inositol administration was associated to reduced serum levels of estrone (- 85.0%) and estradiol (- 14.4%), and increased serum levels of testosterone (+ 23.4%) and dehydroepiandrosterone (+ 13.8%). In addition, epiandrosterone levels were higher (+39%) after treatment. On the other hand, follicle-stimulating hormone, luteinizing hormone and inhibin B did not change. A trend toward a decrease of glycemia, insulinemia and Homeostatic Model Assessment index was observed after D-chiro-inositol treatment, although differences did not reach statistical significance. D-chiro-inositol treatment did not cause any noticeable adverse effect.</p><p><strong>Conclusions: </strong>Increased androgens and decreased estrogens seem to confirm that D-chiro-inositol acts as an aromatase down-modulator, but with a still unknown mechanism of action. This pilot study opens up new perspectives of research and therapeutic applications for D-chiro-inositol at different dosages and length of treatment. Authorization number 005/2020 released by the Local Ethics Committee of Alma Res Fertility Center, Rome.</p><p><strong>Trial registration number: </strong>NCT04615767 (registry: ClinicalTrials.gov) Date of registration: November 3, 2020.</p>","PeriodicalId":8730,"journal":{"name":"Basic and Clinical Andrology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2021-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12610-021-00131-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39070401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LRWD1 expression is regulated through DNA methylation in human testicular embryonal carcinoma cells.","authors":"Jui-Hsiang Hung, Han-Yi Cheng, Yung-Chieh Tsai, Hsien-An Pan, Hany A Omar, Chien-Chih Chiu, Yin-Mei Su, Yung-Ming Lin, Yen-Ni Teng","doi":"10.1186/s12610-021-00130-y","DOIUrl":"10.1186/s12610-021-00130-y","url":null,"abstract":"<p><strong>Background: </strong>Sperm growth and maturation are correlated with the expression levels of Leucine-rich repeat and WD repeat-containing protein 1 (LRWD1), a widely expressed protein in the human testicles. The decrease in LRWD1 cellular level was linked to the reduction in cell growth and mitosis and the rise in cell microtubule atrophy rates. Since DNA methylation has a major regulatory role in gene expression, this study aimed at exploring the effect of the modulation of DNA methylation on LRWD1 expression levels.</p><p><strong>Results: </strong>The results revealed the presence of a CpG island up of 298 bps (- 253 ~ + 45) upon LRWD1 promoter in NT2/D1 cells. The hypermethylation of the LRWD1 promoter was linked to a reduction in the transcription activity in NT2/D1 cells, as indicated by luciferase reporter assay. The methylation activator, floxuridine, confirmed the decrease in the LRWD1 promoter transcriptional activity. On the other hand, 5-Aza-2'-deoxycytidine (5-Aza-dc, methylation inhibitor), significantly augmented LRWD1 promoter activity and the expression levels of mRNA and proteins. Furthermore, DNA methylation status of LRWD1 promoter in human sperm genomic DNA samples was analyzed. The results indicated that methylation of LRWD1 promoter was correlated to sperm activity.</p><p><strong>Conclusions: </strong>Thus, the regulation of LRWD1 expression is correlated with the methylation status of LRWD1 promoter, which played a significant role in the modulation of spermatogenesis, sperm motility, and vitality. Based on these results, the methylation status of LRWD1 promoter may serve as a novel molecular diagnostic marker or a therapeutic target in males' infertility.</p>","PeriodicalId":8730,"journal":{"name":"Basic and Clinical Andrology","volume":null,"pages":null},"PeriodicalIF":2.4,"publicationDate":"2021-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12610-021-00130-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38999162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}