Rare double sex and mab-3-related transcription factor 1 regulatory variants in severe spermatogenic failure.

Abstract:

:The double sex and mab-3-related transcription factor 1 (DMRT1) gene has long been linked to sex-determining pathways across vertebrates and is known to play an essential role in gonadal development and maintenance of spermatogenesis in mice. In humans, the genomic region harboring the DMRT gene cluster has been implicated in disorders of sex development and recently DMRT1 deletions were shown to be associated with non-obstructive azoospermia (NOA). In this work, we have employed different methods to screen a cohort of Portuguese NOA patients for DMRT1 exonic insertions and deletions [by multiplex ligation probe assay (MLPA); n = 68] and point mutations (by Sanger sequencing; n = 155). We have found three novel patient-specific non-coding variants in heterozygosity that were absent from 357 geographically matched controls. One of these is a complex variant with a putative regulatory role (c.-223_-219CGAAA>T), located in the promoter region within a conserved sequence involved in Dmrt1 repression. Moreover, while DMRT1 domains are highly conserved across vertebrates and show reduced levels of diversity in human populations, two rare synonymous substitutions (rs376518776 and rs34946058) and two rare non-coding variants that potentially affect DMRT1 expression and splicing (rs144122237 and rs200423545) were overrepresented in patients when compared with 376 Portuguese controls (301 fertile and 75 normozoospermic). Overall our previous and present results suggest a role of changes in DMRT1 dosage in NOA potentially also through a process of gene misregulation, even though DMRT1 deleterious variants seem to be rare.

journal_name

Andrology

journal_title

Andrology

authors

Lima AC,Carvalho F,Gonçalves J,Fernandes S,Marques PI,Sousa M,Barros A,Seixas S,Amorim A,Conrad DF,Lopes AM

doi

10.1111/andr.12063

subject

Has Abstract

pub_date

2015-09-01 00:00:00

pages

825-33

issue

5

eissn

2047-2919

issn

2047-2927

journal_volume

3

pub_type

杂志文章
  • Intracavernous delivery of Dickkopf3 gene or peptide rescues erectile function through enhanced cavernous angiogenesis in the diabetic mouse.

    abstract:BACKGROUND:Severe peripheral angiopathy in patients with diabetes is a major contributing factor for low response rate to phosphodiesterase-5 inhibitors. OBJECTIVES:To examine whether and how Dickkopf3 (DKK3), a secreted modulator of the Wnt pathway that known to be involved in endothelial cell repair and vascular pro...

    journal_title:Andrology

    pub_type: 杂志文章

    doi:10.1111/andr.12784

    authors: Song KM,Kim WJ,Choi MJ,Limanjaya A,Ghatak K,Minh NN,Ock J,Yin GN,Hong SS,Suh JK,Ryu JK

    更新日期:2020-09-01 00:00:00

  • Levels of l-arginine and l-citrulline in patients with erectile dysfunction of different etiology.

    abstract::Nitric oxide is a physiologic signal essential to penile erection. l-citrulline (l-Cit) is converted into l-arginine (l-Arg), the precursor from which nitric oxide is generated. The level of l-Arg and l-Cit in the field of male sexual function remains relatively underexplored. The aim of the study was to evaluate the ...

    journal_title:Andrology

    pub_type: 杂志文章

    doi:10.1111/andr.12293

    authors: Barassi A,Corsi Romanelli MM,Pezzilli R,Damele CA,Vaccalluzzo L,Goi G,Papini N,Colpi GM,Massaccesi L,Melzi d'Eril GV

    更新日期:2017-03-01 00:00:00

  • Identification of the G protein-coupled estrogen receptor (GPER) in human prostate: expression site of the estrogen receptor in the benign and neoplastic gland.

    abstract::Estrogens are involved in growth, differentiation and pathogenesis of human prostate through the mediation of the classical estrogen receptors ERα and ERβ. The G protein-coupled estrogen receptor (GPER) is a 'novel' mediator of estrogen signaling which has been recently recognized in some human reproductive tissues, b...

    journal_title:Andrology

    pub_type: 杂志文章

    doi:10.1111/andr.12131

    authors: Rago V,Romeo F,Giordano F,Ferraro A,Carpino A

    更新日期:2016-01-01 00:00:00

  • Male soy food intake was not associated with in vitro fertilization outcomes among couples attending a fertility center.

    abstract::Male factor etiology may be a contributing factor in up to 60% of infertility cases. Dietary intake of phytoestrogens has been related to abnormal semen quality and hormone levels. However, its effect on couple fecundity is still unclear. Intake of soy products was assessed in 184 men from couples undergoing infertili...

    journal_title:Andrology

    pub_type: 杂志文章

    doi:10.1111/andr.12046

    authors: Mínguez-Alarcón L,Afeiche MC,Chiu YH,Vanegas JC,Williams PL,Tanrikut C,Toth TL,Hauser R,Chavarro JE

    更新日期:2015-07-01 00:00:00

  • Tamoxifen in men: a review of adverse events.

    abstract::Tamoxifen is an off-label option to treat men for breast cancer, infertility, and idiopathic gynecomastia. Lately, tamoxifen has been proposed as a treatment to prevent gynecomastia in prostate cancer patients receiving antiandrogen therapy. We reviewed the adverse events (AEs) reported in studies of men prescribed ta...

    journal_title:Andrology

    pub_type: 杂志文章,评审

    doi:10.1111/andr.12197

    authors: Wibowo E,Pollock PA,Hollis N,Wassersug RJ

    更新日期:2016-09-01 00:00:00

  • The mouse transcription factor-like 5 gene encodes a protein localized in the manchette and centriole of the elongating spermatid.

    abstract::Spermiogenesis is the final phase of spermatogenesis. During this process, haploid round spermatids differentiate into spermatozoa, with dramatic morphological changes, including elongation and condensation of the nuclei, and formation of the flagella. Meig1 is one of many genes involved in the regulation of this proc...

    journal_title:Andrology

    pub_type: 杂志文章

    doi:10.1111/j.2047-2927.2013.00069.x

    authors: Shi Y,Zhang L,Song S,Teves ME,Li H,Wang Z,Hess RA,Jiang G,Zhang Z

    更新日期:2013-05-01 00:00:00

  • Potential confounding factors in measurement of specific cell-free seminal mRNAs and microRNAs derived from human reproductive organs.

    abstract::Cell-free seminal RNA (cfs-RNA) is mixed transcripts derived from male reproductive organs, and is potential biomarker for the research and diagnosis of male reproductive-related diseases. However, some clinical factors, including age, asymptomatic Ureaplasma urealyticum (UU) infection, scrotal heat stress, abstinence...

    journal_title:Andrology

    pub_type: 杂志文章

    doi:10.1111/andr.12238

    authors: Dong TT,Yu Q,Qing XR,Ma XL,Dong WW,Shi J,Li HG

    更新日期:2016-11-01 00:00:00

  • p53 and MDM2 expression in primary and metastatic testicular germ cell tumors: Association with clinical outcome.

    abstract:BACKGROUND:Testicular germ cell tumors (TGCTs) are highly sensitive to platinum-based chemotherapy, and wild-type p53 seems to play a pivotal role in this susceptibility. On the other hand, overexpression of MDM2 seems to entail treatment resistance and unfavorable prognosis. OBJECTIVES:We aimed to describe p53 and MD...

    journal_title:Andrology

    pub_type: 杂志文章

    doi:10.1111/andr.12814

    authors: Lobo J,Alzamora MA,Guimarães R,Cantante M,Lopes P,Braga I,Maurício J,Jerónimo C,Henrique R

    更新日期:2020-09-01 00:00:00

  • Functions of genes related to testicular germ cell tumour development.

    abstract:OBJECTIVE:Testicular germ cell tumour (TGCT) is a malignancy with a high heritable component. The inherited risk is polygenic, and around 50 susceptibility genes are identified. The functional role of the gene products for TGCT development is not well understood. The focus of this review is functional studies of geneti...

    journal_title:Andrology

    pub_type: 杂志文章,评审

    doi:10.1111/andr.12663

    authors: Das MK,Kleppa L,Haugen TB

    更新日期:2019-07-01 00:00:00

  • Conditional survival after surgery for patients with penile cancer.

    abstract:BACKGROUND:Penile cancer represents a rare pathology whose natural history of treatment is poorly understood. OBJECTIVE:To illustrate the dynamic survival profiles in surgically treated patients with squamous cell carcinoma of the penis (SCCP) using the conditional survival (CS) estimates. MATERIALS AND METHODS:Patie...

    journal_title:Andrology

    pub_type: 杂志文章

    doi:10.1111/andr.12856

    authors: Liu W,Luo Y,Wang G,Li N,Wang Z,Lei J,Wang X

    更新日期:2020-11-01 00:00:00

  • Lower birthweight and left-/mixed-handedness are associated with intensified age-related sex steroid decline in men. Findings from the Men's Health 40+ Study.

    abstract::In males, age-related decline in free testosterone (T) and dehydroepiandrosterone (DHEA) by 2-3% per year has been reported. Estradiol (E2) and progesterone (P) seem to decrease as well, but to a lesser extent. Lower sex steroid levels in men have been related to physical and mental symptoms. Low birthweight and left-...

    journal_title:Andrology

    pub_type: 杂志文章

    doi:10.1111/andr.12516

    authors: Hoppler S,Walther A,La Marca-Ghaemmaghami P,Ehlert U

    更新日期:2018-11-01 00:00:00

  • The SET protein promotes androgen production in testicular Leydig cells.

    abstract::Approximately 40% of middle-aged men exhibit symptoms of late-onset hypogonadism (LOH). However, the mechanism of androgen deficiency is still currently unclear. As shown in our previous studies, the SET protein is expressed in testicular Leydig cells and ovarian granule cells. This study was designed to investigate t...

    journal_title:Andrology

    pub_type: 杂志文章

    doi:10.1111/andr.12476

    authors: Zhang B,Ma W,Zhu Q,Xu W,Gao L,Xu B,Xu S,Gao C,Gao L,Liu J,Cui Y

    更新日期:2018-05-01 00:00:00

  • Male partners of infertile couples with congenital unilateral absence of the vas deferens are mainly non-azoospermic.

    abstract:BACKGROUND:Men with congenital unilateral absence of vas deferens were reported to be mainly azoospermic, with both unilateral renal absence and mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) but some have neither. OBJECTIVES:To assess whether in infertile couples the male partners with co...

    journal_title:Andrology

    pub_type: 杂志文章

    doi:10.1111/andr.12749

    authors: Mieusset R,Bieth E,Daudin M,Isus F,Delaunay B,Bujan L,Monteil L,Fauquet I,Huyghe E,Hamdi SM

    更新日期:2020-05-01 00:00:00

  • Growth hormone (GH) activity is associated with increased serum oestradiol and reduced anti-Müllerian hormone in healthy male volunteers treated with GH and a GH antagonist.

    abstract::Growth hormone (GH) and insulin-like growth factor I (IGF-I) receptors are present on pituitary gonadotrophs and on testicular Leydig and Sertoli cells. Thus, the GH/IGF-I system may modulate the pituitary-gonadal axis in males. This is a randomized cross-over study. Eight healthy male volunteers (mean age 35, range 2...

    journal_title:Andrology

    pub_type: 杂志文章,随机对照试验

    doi:10.1111/j.2047-2927.2013.00096.x

    authors: Andreassen M,Frystyk J,Faber J,Kristensen LØ,Juul A

    更新日期:2013-07-01 00:00:00

  • The association between sperm head elongation and semen quality.

    abstract:BACKGROUND:Previous studies suggested that sperm head shape may serve as an effective indicator of semen quality. However, there lacks research with large sample and quantitative measurement. OBJECTIVES:The objective of this retrospective study was to explore the association between sperm head elongation (Width/Length...

    journal_title:Andrology

    pub_type: 杂志文章

    doi:10.1111/andr.12619

    authors: Chen F,Gao L,Zhou H,Guo L,Chen Q,Gan Y,Sun X,Li Q,Wang K

    更新日期:2019-11-01 00:00:00

  • Decreased activity of superoxide dismutase in the seminal plasma of infertile men correlates with increased sperm deoxyribonucleic acid fragmentation during the first hours after sperm donation.

    abstract::Sperm DNA fragmentation varies between individuals and is more pronounced with increased patient age and time after sperm donation. The intensification of DNA fragmentation depends on the balance of the oxidoreductive system, which is regulated mainly by two enzymes - superoxide dismutase (SOD) and catalase. The objec...

    journal_title:Andrology

    pub_type: 杂志文章

    doi:10.1111/andr.12061

    authors: Wdowiak A,Bakalczuk S,Bakalczuk G

    更新日期:2015-07-01 00:00:00

  • Historical Vignette: Attempted treatment of Sigmund Freud's oral squamous cell carcinoma by vasectomy (Steinach Operation) in 1923.

    abstract:BACKGROUND:At the beginning of the 20th century, the Viennese physiologist Eugen Steinach proposed to treat the effects of physiological ageing by vasectomy. After experimenting his theory with animal, he published his results, and convinced scientists to apply this method to humans (ie men). The scientific community h...

    journal_title:Andrology

    pub_type: 杂志文章

    doi:10.1111/andr.12729

    authors: Benmoussa N,Charlier P,Rebibo JD

    更新日期:2020-05-01 00:00:00

  • Supplementing cryopreservation media with reduced glutathione increases fertility and prolificacy of sows inseminated with frozen-thawed boar semen.

    abstract::The main aim of this work was to evaluate how supplementing freezing media with reduced glutathione (GSH) affected the 'in vivo' fertilizing ability of boar semen subjected to cryopreservation procedures. With this purpose, 12 ejaculates coming from 12 boars were cryopreserved in the presence or absence of 2 mm GSH, w...

    journal_title:Andrology

    pub_type: 杂志文章

    doi:10.1111/j.2047-2927.2013.00144.x

    authors: Estrada E,Rodríguez-Gil JE,Rocha LG,Balasch S,Bonet S,Yeste M

    更新日期:2014-01-01 00:00:00

  • European academy of andrology guidelines on Klinefelter Syndrome Endorsing Organization: European Society of Endocrinology.

    abstract:BACKGROUND:Knowledge about Klinefelter syndrome (KS) has increased substantially since its first description almost 80 years ago. A variety of treatment options concerning the spectrum of symptoms associated with KS exists, also regarding aspects beyond testicular dysfunction. Nevertheless, the diagnostic rate is still...

    journal_title:Andrology

    pub_type: 杂志文章,评审

    doi:10.1111/andr.12909

    authors: Zitzmann M,Aksglaede L,Corona G,Isidori AM,Juul A,T'Sjoen G,Kliesch S,D'Hauwers K,Toppari J,Słowikowska-Hilczer J,Tüttelmann F,Ferlin A

    更新日期:2021-01-01 00:00:00

  • Testosterone replacement in transgenic sickle cell mice controls priapic activity and upregulates PDE5 expression and eNOS activity in the penis.

    abstract::Sickle cell disease (SCD)-associated priapism is characterized by decreased nitric oxide (NO) signaling and downregulated phosphodiesterase (PDE)5 protein expression and activity in the penis. Priapism is also associated with testosterone deficiency, but molecular mechanisms underlying testosterone effects in the peni...

    journal_title:Andrology

    pub_type: 杂志文章

    doi:10.1111/andr.12442

    authors: Musicki B,Karakus S,Akakpo W,Silva FH,Liu J,Chen H,Zirkin BR,Burnett AL

    更新日期:2018-01-01 00:00:00

  • Cytological evaluation of spermatogenesis: a novel and simple diagnostic method to assess spermatogenesis in non-obstructive azoospermia using testicular sperm extraction specimens.

    abstract::Most of the non-obstructive azoospermia (NOA)-patients have only focal spermatogenesis which results in insufficient numbers of spermatozoa to reach the ejaculate. In ≈50% of these NOA-patients testicular sperm extraction (TESE) is successful and intracytoplasmic sperm injection (ICSI) is pursued. We studied whether (...

    journal_title:Andrology

    pub_type: 杂志文章

    doi:10.1111/andr.12023

    authors: Hessel M,de Vries M,D'Hauwers KW,Fleischer K,Hulsbergen-van de Kaa CA,Braat DD,Ramos L

    更新日期:2015-05-01 00:00:00

  • Altered gene expression signature of early stages of the germ line supports the pre-meiotic origin of human spermatogenic failure.

    abstract::The molecular basis of spermatogenic failure (SpF) is still largely unknown. Accumulating evidence suggests that a series of specific events such as meiosis, are determined at the early stage of spermatogenesis. This study aims to assess the expression profile of pre-meiotic genes of infertile testicular biopsies that...

    journal_title:Andrology

    pub_type: 杂志文章

    doi:10.1111/j.2047-2927.2014.00217.x

    authors: Bonache S,Algaba F,Franco E,Bassas L,Larriba S

    更新日期:2014-07-01 00:00:00

  • Effect of equilibration times, freezing, and thawing rates on post-thaw quality of buffalo (Bubalus bubalis) bull spermatozoa.

    abstract::The effects of equilibration times (E1, 2 h; E2, 4 h; E3, 6 h), freezing rates (FR1, manual, 5 cm above liquid nitrogen (LN2 ) for 10 min, plunging in LN2 ; FR2, programmable ultra-fast, holding at +4 °C for 2 min, from 4 to -10 °C at -10 °C/min, from -10 to -20 °C at -15 °C/min, from -20 to -120 °C at -60 °C/min, hol...

    journal_title:Andrology

    pub_type: 杂志文章

    doi:10.1111/andr.12214

    authors: Shah SA,Andrabi SM,Qureshi IZ

    更新日期:2016-09-01 00:00:00

  • Impact of time from diagnosis to treatment on erectile function outcomes after radical prostatectomy.

    abstract:BACKGROUND:Concerns exist about the effect of delaying treatment for prostate cancer (PCa) regarding both oncological and functional outcomes after radical prostatectomy (RP). OBJECTIVE:To assess the impact of time from diagnosis to RP on post-operative erectile function (EF) outcomes. MATERIALS AND METHODS:We analyz...

    journal_title:Andrology

    pub_type: 杂志文章

    doi:10.1111/andr.12699

    authors: Schifano N,Capogrosso P,Pozzi E,Ventimiglia E,Cazzaniga W,Matloob R,Gandaglia G,Dehò F,Briganti A,Montorsi F,Salonia A

    更新日期:2020-03-01 00:00:00

  • Endocrine and molecular investigations in a cohort of 25 adolescent males with prominent/persistent pubertal gynecomastia.

    abstract::Pubertal gynecomastia is a common condition observed in up to 65% of adolescent males. It is usually idiopathic and tends to regress within 1-2 years. In this descriptive cross-sectional study, we investigated 25 adolescent males with prominent (>B3) and/or persistent (>2 years) pubertal gynecomastia (P/PPG) to determ...

    journal_title:Andrology

    pub_type: 杂志文章

    doi:10.1111/andr.12145

    authors: Paris F,Gaspari L,Mbou F,Philibert P,Audran F,Morel Y,Biason-Lauber A,Sultan C

    更新日期:2016-03-01 00:00:00

  • A new Bayesian network-based approach to the analysis of sperm motility: application in the study of tench (Tinca tinca) semen.

    abstract::In this study a Bayesian network (BN) has been built for the study of the objective motility of Tinca tinca spermatozoa (spz). Semen from eight 2-year-old sexually mature male tenchs was obtained and motility analyses were performed at 6-17, 23-34 and 40-51 s after activation, using computer-assisted sperm analysis (C...

    journal_title:Andrology

    pub_type: 杂志文章

    doi:10.1111/andr.12071

    authors: Gil Anaya MC,Calle F,Pérez CJ,Martín-Hidalgo D,Fallola C,Bragado MJ,García-Marín LJ,Oropesa AL

    更新日期:2015-09-01 00:00:00

  • Germline genome protection: implications for gamete quality and germ cell tumorigenesis.

    abstract:BACKGROUND:Germ cells have a unique and critical role as the conduit for hereditary information and therefore employ multiple strategies to protect genomic integrity and avoid mutations. Unlike somatic cells, which often respond to DNA damage by arresting the cell cycle and conducting DNA repair, germ cells as well as ...

    journal_title:Andrology

    pub_type: 杂志文章,评审

    doi:10.1111/andr.12651

    authors: Bloom JC,Loehr AR,Schimenti JC,Weiss RS

    更新日期:2019-07-01 00:00:00

  • The role of resistin on metabolic syndrome-induced erectile dysfunction and the possible therapeutic effect of Boldine.

    abstract:BACKGROUND:Resistin is known as a potential mediator of obesity-associated insulin resistance. The high resistin level disrupts nitric oxide (NO)-mediated relaxation which is also important in erectile function. An antioxidant alkaloid, Boldine, is known as anti-diabetic and protects endothelial functions. OBJECTIVES:...

    journal_title:Andrology

    pub_type: 杂志文章

    doi:10.1111/andr.12853

    authors: Kara E,Kahraman E,Dayar E,Yetik Anacak G,Demir O,Gidener S,Atabey N,Durmus N

    更新日期:2020-11-01 00:00:00

  • Biology of childhood germ cell tumours, focussing on the significance of microRNAs.

    abstract::Genomic and protein-coding transcriptomic data have suggested that germ cell tumours (GCTs) of childhood are biologically distinct from those of adulthood. Global messenger RNA profiles segregate malignant GCTs primarily by histology, but then also by age, with numerous transcripts showing age-related differential exp...

    journal_title:Andrology

    pub_type: 杂志文章,评审

    doi:10.1111/andr.277

    authors: Murray MJ,Nicholson JC,Coleman N

    更新日期:2015-01-01 00:00:00

  • Sperm cephalic vacuoles: new arguments for their non acrosomal origin in two cases of total globozoospermia.

    abstract::To add new arguments concerning the origin of the sperm-head vacuoles observed under high magnification with interference contrast microscopy, we carried out in two patients with total globozoospermia confirmed using transmission electron microscopy (TEM), a detailed sperm morphometric analysis with high magnification...

    journal_title:Andrology

    pub_type: 杂志文章

    doi:10.1111/j.2047-2927.2012.00011.x

    authors: Gatimel N,Léandri RD,Foliguet B,Bujan L,Parinaud J

    更新日期:2013-01-01 00:00:00