Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA–binding protein gene

Reijo, Renee A.; Lee, Tien-Yi; Salo, Pia; Alagappan, Raaji; Brown, Laura G.; Rosenberg, Michael; Rozen, Steve; Jaffe, Tom; Straus, Daniel S.; Hovatta, Outi; Chapelle, Albert de la; Silber, Sherman J.; Page, David C.

doi:10.1038/ng0895-383

Cited by 1,104 publications

(568 citation statements)

References 41 publications

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“…Northern hybridization and RT-PCR were performed as described (1). Tissues were homogenized in Trizol according to instructions (GIBCO͞BRL, Bethesda).…”

Section: Methodsmentioning

confidence: 99%

“…This finding suggests that DAZ proteins may function with interacting proteins to regulate translation. (ii) Four of the proteins are encoded by loci shown genetically to be required for fertility in other organisms (PUM2, BOL, hQK3, and DAZL) (1,8,(17)(18)(19). (iii) Five of the proteins have been shown biochemically to interact with DAZ [BOL, DZIP1, DZIP2, hQK3 (data not shown)] and DAZL (14,20,21).…”

Section: Identification Of Daz-interacting Proteinsmentioning

confidence: 99%

“…Men with deletions encompassing the Y-chromosome DAZ gene cluster have defects in spermatogenesis that are detected initially in the stem cell population. These men frequently lack all germ cells, including the spermatogonial stem cells, and only somatic cells are present in testicular tissue (1)(2)(3). In addition, expression of the DAZ gene and its ancestral, autosomal homolog, DAZL, only occurs in germ cells; DAZ is expressed in males, and DAZL is expressed in males and females (4,5).…”

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confidence: 99%

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Human Pumilio-2 is expressed in embryonic stem cells and germ cells and interacts with DAZ (Deleted in AZoospermia) and DAZ-Like proteins

Moore

Jaruzelska

Fox

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

208

215

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Early in development, a part of the embryo is set aside to become the germ cell lineage that will ultimately differentiate to form sperm and eggs and transmit genetic information to the next generation. Men with deletions encompassing the Y-chromosome DAZ genes have few or no germ cells but are otherwise healthy, indicating they harbor specific defects in formation or maintenance of germ cells. A DAZ homolog, DAZL (DAZ-Like), is found in diverse organisms, including humans and is required for germ cell development in males and͞or females. We identified proteins that interact with DAZ proteins to better understand their function in human germ cells. Here, we show that PUM2, a human homolog of Pumilio, a protein required to maintain germ line stem cells in Drosophila and Caenorhabditis elegans, forms a stable complex with DAZ through the same functional domain required for RNA binding, protein-protein interactions and rescue of Pumilio mutations in flies. We also show that PUM2 is expressed predominantly in human embryonic stem cells and germ cells and colocalizes with DAZ and DAZL in germ cells. These data implicate PUM2 as a component of conserved cellular machinery that may be required for germ cell development.A ll stem cells have potential to differentiate or proliferate mitotically. These potentials must be balanced for the stem cell population to be maintained. If differentiation exceeds proliferation, the stem cell population is not maintained. Evidence in humans suggests that the DAZ genes function early in the germ line stem cells. Men with deletions encompassing the Y-chromosome DAZ gene cluster have defects in spermatogenesis that are detected initially in the stem cell population. These men frequently lack all germ cells, including the spermatogonial stem cells, and only somatic cells are present in testicular tissue (1-3). In addition, expression of the DAZ gene and its ancestral, autosomal homolog, DAZL, only occurs in germ cells; DAZ is expressed in males, and DAZL is expressed in males and females (4, 5). Evidence from model organisms also suggests the DAZ genes function in germ cell maintenance. The Xenopus homolog of DAZ, Xdazl, is expressed in a region of the early oocyte that contains the germ plasm that is required for formation and maintenance of the germ cell lineage (6, 7). Inhibition of Xdazl leads to loss of the primordial germ cells (6, 7). Finally, the DAZ homolog in mice, Dazl, is most abundantly expressed in premeiotic germ cells; disruption of this gene causes depletion of germ cells beginning prenatally (8-10). DAZ and DAZL homologs may function interchangeably as suggested by the observation that a human DAZ transgene can partially rescue a mouse Dazl mutation (11). To shed light on how DAZ genes might function in human germ cells, we sought to identify proteins that interact with DAZ proteins. Materials and MethodsTwo-Hybrid Screening of DAZ-Interacting Proteins. The yeast two-hybrid system was used to identify proteins that interact with a DAZ:GAL4 DNA-binding domain fusion prot...

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“…Northern hybridization and RT-PCR were performed as described (1). Tissues were homogenized in Trizol according to instructions (GIBCO͞BRL, Bethesda).…”

Section: Methodsmentioning

confidence: 99%

Section: Identification Of Daz-interacting Proteinsmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Human Pumilio-2 is expressed in embryonic stem cells and germ cells and interacts with DAZ (Deleted in AZoospermia) and DAZ-Like proteins

Moore

Jaruzelska

Fox

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

208

215

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“…Genetic causes of azoospermia include chromosomal abnormalities, Y chromosome microdeletions, and specific mutations or deletions of several Y chromosomal genes 2, 3. Thus, in 1995, it was demonstrated that DAZ mutations (Yq11.23) cause various forms of human male infertility that range from oligospermia to azoospermia 4, 5. In 1997, it was reported that RBMY (Yq11.223) mutations cause azoospermia via meiotic arrest5, 6 and, in 1999, it was shown that USP9Y (Yq11.2) mutations lead to azoospermia that is secondary to hypospermatogenesis 5, 7.…”

Section: Introductionmentioning

confidence: 99%

Human male infertility and its genetic causes

Miyamoto

Minase

Shin

et al. 2017

Reprod Medicine & Biology

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BackgroundInfertility affects about 15% of couples who wish to have children and half of these cases are associated with male factors. Genetic causes of azoospermia include chromosomal abnormalities, Y chromosome microdeletions, and specific mutations/deletions of several Y chromosome genes. Many researchers have analyzed genes in the AZF region on the Y chromosome; however, in 2003 the SYCP3 gene on chromosome 12 (12q23) was identified as causing azoospermia by meiotic arrest through a point mutation.MethodsWe mainly describe the SYCP3 and PLK4 genes that we have studied in our laboratory, and add comments on other genes associated with human male infertility.ResultsUp to now, The 17 genes causing male infertility by their mutation have been reported in human.ConclusionsInfertility caused by nonobstructive azoospermia (NOA) is very important in the field of assisted reproductive technology. Even with the aid of chromosomal analysis, ultrasonography of the testis, and detailed endocrinology, only MD‐TESE can confirm the presence of immature spermatozoa in the testes. We strongly hope that these studies help clinics avoid ineffective MD‐TESE procedures.

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“…While many members of the hnRNP family were discovered two or more decades ago, a family member relevant to spermatogenesis was isolated more recently. This hnRNP protein-DAZAP1-was isolated on the basis of its interaction with DAZ, a germ-cell-specific RNA-binding protein encoded on the Y chromosome that is deleted in 10 per cent of infertile men with idiopathic azoospermia (Reijo et al 1995(Reijo et al , 1996Tsui et al 2000). To determine the in vivo function of DAZAP1, Hsu et al (2008) generated Dazap1-mutant mice carrying either a floxed neomycin resistant (Fn) hypomorphic allele or a null allele.…”

Section: Rna-binding Proteins That Regulate Spermatogenesismentioning

confidence: 99%

Transcription and post-transcriptional regulation of spermatogenesis

Bettegowda

Wilkinson

2010

Phil. Trans. R. Soc. B

143

101

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Spermatogenesis in mammals is achieved by multiple players that pursue a common goal of generating mature spermatozoa. The developmental processes acting on male germ cells that culminate in the production of the functional spermatozoa are regulated at both the transcription and posttranscriptional levels. This review addresses recent progress towards understanding such regulatory mechanisms and identifies future challenges to be addressed in this field. We focus on transcription factors, chromatin-associated factors and RNA-binding proteins necessary for spermatogenesis and/ or sperm maturation. Understanding the molecular mechanisms that govern spermatogenesis has enormous implications for new contraceptive approaches and treatments for infertility.

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Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA–binding protein gene

Cited by 1,104 publications

References 41 publications

Human Pumilio-2 is expressed in embryonic stem cells and germ cells and interacts with DAZ (Deleted in AZoospermia) and DAZ-Like proteins

Human Pumilio-2 is expressed in embryonic stem cells and germ cells and interacts with DAZ (Deleted in AZoospermia) and DAZ-Like proteins

Human male infertility and its genetic causes

Transcription and post-transcriptional regulation of spermatogenesis

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