DAZ (Deleted In AZoospermia) genes encoie proteins located in human late spermatids and In sperm tails

Habermann, Barbara; Hf, Mi; Edelmann, A; Bohring, C.; It, Bäckert; Kiesewetter, F.; Aumüller, Gerhard; Ph, Vogt

doi:10.1093/humrep/13.2.363

Cited by 104 publications

(71 citation statements)

References 21 publications

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“…Since also DAZ proteins have been found to accumulate in late spermatids and human sperm tails " Fig. (6)" [206] it can be assumed that the functional activities of the multiple DAZ genes in human spermatogenesis significantly exceeds beyond the function of the single DAZL1 gene in mouse spermatogenesis. …”

Section: Dazl1 Expression Is Diagnostic For the Presence Of Germ Cellsmentioning

confidence: 99%

Molecular Genetic of Human Male Infertility: From Genes to New Therapeutic Perspectives

Vogt¹

2004

CPD

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Genetic lesions causing human male infertility are manifold. Besides gross chromosomal aneuploidies and rearrangements, microdeletions and single gene defects can interfere with male fertility. Male fertility is not only dependent on genes controlling the male germ line but also on genes of the networks functional for male gonad development and male somatic development, respectively. It is popular to unravel these netweorks with mouse gene knock-out mutants displaying reproductive defects. However, substantial arguments can be given for more functional studies directly on the human genes, because multiple reproductive proteins evolve quickly most likely for adopting to the specific needs of the species class. Prominent examples are mutations of the FSHR gene causing different pathologies in mouse and human and the DAZ gene family not found in the mouse genome but in the human genome with an essential male fertility function. Therefore this review is focussed on a comprehensive overview of human genes known with mutations causing male infertility (AR; AZF gene families; CFTR, DM-1, DNAH gene family, FGFR1, FSHR, INSL3, KAL-1, LGR8-GREAT, LHR, POLG). Then some human genes are described well recognised as functional in spermatogenesis and male fertility although gene specific mutations causing infertility were not yet identified (CREM, CDY1, DAZL1, PHGPx, PRM-1, PRM-2). They are designated as "spermatogenesis phase marker" or "male fertility index" genes, because they are useful tools for diagnosing the patient´s´ spermatogenesis disruption phase and for predicting the presence and quality of his mature sperms. Current therapeutic protocols for human male infertility do usually not cure the specific gene defect but try to bypass it using Artificial Reproductive Technology (ART). Putative imprinting defects in the early embryo probably associated with the used ART protocol and an increase of chromosome abnormalities in the ART offspring now strongly asks for a significant improvement of this outcome requesting urgently more basic research on the genes functioning in the human male germ line and during early human embryogenesis.

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Section: Dazl1 Expression Is Diagnostic For the Presence Of Germ Cellsmentioning

confidence: 99%

Molecular Genetic of Human Male Infertility: From Genes to New Therapeutic Perspectives

Vogt¹

2004

CPD

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“…In immunostaining experiments using antibodies probably specific for DAZ2, we found DAZ immunoreactivity in the innermost layer of the mature sperm cell epithelium, preferentially in their so-called residual bodies immediately prior to spermiation and in the tails of ejaculated spermatozoa [122] . From these findings, we can deduce a function for DAZ proteins in the RNA metabolism of late spermatids, presumably in the storage or transport of testis-specific mRNAs, the translation of which is repressed until the formation of mature spermatozoa.…”

Section: Azfc Gene Deletions and Male Infertilitymentioning

confidence: 84%

“…Expression of BOLL and DAZL proteins was mainly found in germ cells before meiosis [121] , whereas DAZ proteins were mainly expressed during the postmeiotic germ cell phase in late spermatids and spermatozoa [122] .…”

Section: Azfc Gene Deletions and Male Infertilitymentioning

confidence: 99%

Human Y Chromosome and Male Infertility: Forward and Back from Azoospermia Factor Chromatin Structure to Azoospermia Factor Gene Function

Vogt¹,

Bender²,

Zimmer³

et al. 2017

Genetics of Human Infertility

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In the euchromatic part of the long arm of the human Y chromosome (Yq11) at least 13 Y genes encoding proteins and expressed in male germ cells were found in 3 distinct genomic Y regions frequently deleted in infertile men with idiopathic azoospermia, i.e., for unknown reasons no mature sperm were found in their semen fluid. Accordingly, they were designated as azoospermia factor (AZF) regions: AZFa, AZFb, and AZFc. Additionally, 10 Y genes called "testis-specific transcript Y" ( TTTY ) genes were mapped in the same AZF intervals. They belong to the long non-coding RNA gene pool in human germ cells because they seem to lack any protein-coding potential. Distinct chromatin regions in Yq11 overlapping with AZFb and AZFc are supposed to be involved in the premeiotic X and Y chromosome pairing and inactivation process controlling male germ cell meiosis. It can thus be assumed that the germ line function of the AZF loci in Yq11 may be not only based on the expression of some germ cell proteins, but also on the expression of some germ cell-specific TTTY transcripts and a locally dynamic and specific chromatin folding structure probably controlled by some germ cell-specific nuclear proteins.

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“…The gr/gr deletions (which is most frequently observed) remove almost half the gene content of AZFc involving two of the four copies of the DAZ (deleted in azoospermia) gene, one of the two copies of CDY1 (chromodomain protein on Y, 1) and BPY2 (basic protein Y-2) genes; the b1/b3 and b2/b3 deletions also remove the similar amount of genetic material and the same genes [14]. Amongst these three, the DAZ and CDY1 are the key genes required for spermatogenesis [15][16][17][18]. The DAZ gene has four functional copies in AZFc locus that encode for a RNA binding protein and is essential to promote germ cell progression to meiosis [15,17].…”

Section: Introductionmentioning

confidence: 99%

“…Amongst these three, the DAZ and CDY1 are the key genes required for spermatogenesis [15][16][17][18]. The DAZ gene has four functional copies in AZFc locus that encode for a RNA binding protein and is essential to promote germ cell progression to meiosis [15,17]. The CDY1 gene exists in two copies in the AZFc locus and encodes for chromodomain protein 1 which is postulated to be involved in the hyperacetylation of histones in the maturing spermatids [16,18].…”

Section: Introductionmentioning

confidence: 99%

Susceptibility of gr/gr rearrangements to azoospermia or oligozoospermia is dependent on DAZ and CDY1 gene copy deletions

Sen

Ambulkar

Hinduja

et al. 2015

J Assist Reprod Genet

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Purpose The purpose of this study was to determine the association of AZFc subdeletions (gr/gr, b1/b3 and b2/b3) and deletion of DAZ and CDY1 gene copies with male infertility Methods Three hundred twelve controls, 172 azoospermic and 343 oligozoospermic subjects were subjected to AZFc subdeletion typing by STS PCR. Deletion of DAZ and CDY1 gene copies was done using sequence family variant analysis. Sperm concentration and motility were compared between men with and without AZFc subdeletions. Effect of the AZFc subdeletions on ICSI outcome was evaluated. Results Amongst the three AZFc subdeletions, the frequency of gr/gr was higher in oligozoospermic (10.5 %) and azoospermic (11.6 %) men as compared to controls (5.1 %). In men with AZFc subdeltions, loss of two DAZ and one CDY1 gene copy made them highly susceptible to azoospermia and severe oligozoospermia with OR of 29.7 and 26, respectively. These subdeletions had no effect on ICSI outcome, albeit there were an increased number of poor quality embryos in AZFc subdeleted group. Conclusion AZFc subdeletions are a major risk factor for male infertility in the Indian population. In the subjects with AZFc subdeletions, the deletion of DAZ and CDY1 gene copies increases its susceptibility to azoospermia or severe oligozoospermia. Since these deletions can be vertically transmitted to the future male offspring by ICSI, it will be essential to counsel the couples for the transmission of the genetic defect in the male offspring born after assisted reproduction and the risk of perpetuating infertility in future generation.

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DAZ (Deleted In AZoospermia) genes encoie proteins located in human late spermatids and In sperm tails

Cited by 104 publications

References 21 publications

Molecular Genetic of Human Male Infertility: From Genes to New Therapeutic Perspectives

Molecular Genetic of Human Male Infertility: From Genes to New Therapeutic Perspectives

Human Y Chromosome and Male Infertility: Forward and Back from Azoospermia Factor Chromatin Structure to Azoospermia Factor Gene Function

Susceptibility of gr/gr rearrangements to azoospermia or oligozoospermia is dependent on DAZ and CDY1 gene copy deletions

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