A comprehensive review of genetics and genetic testing in azoospermia

Hamada, Alaa; Esteves, Sandro C.; Agarwal, Ashok

doi:10.6061/clinics/2013(sup01)06

Cited by 155 publications

(144 citation statements)

References 281 publications

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“…(2) Non-obstructive azoospermia (NOA) accounting for approximately 60% of men with azoospermia, in which spermatogenesis is inactive and thus sperm cells are not generated. The pathophysiology of NOA is characterised by the absence of sperm cells due to a Sertoli cell-only histology pattern, where only Sertoli cells line the seminiferous tubules (Sertoli cell-only syndrome (SCOS), maturation arrest, where spermatogenesis is not complete and may be arrested at one or more levels of spermatogenesis; hypospermatogenesis, where complete spermatogenesis is present but only few mature sperm cells can be observed or mixed patterns 4. NOA is a severe form of male infertility, with limited treatment options and low fertility success rates 2…”

Section: Introductionmentioning

confidence: 99%

Mutation in TDRD9 causes non-obstructive azoospermia in infertile men

et al. 2017

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Section: Introductionmentioning

confidence: 99%

Mutation in TDRD9 causes non-obstructive azoospermia in infertile men

et al. 2017

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“…Nonobstructive azoospermia (NOA), in which the testicles fail to produce mature sperm in the ejaculate because of abnormal spermatogenesis, accounts for approximately onehalf of azoospermia cases (2,3). NOA is a heterogeneous disorder caused by complex genetic and environmental factors.…”

mentioning

confidence: 99%

Major spliceosome defects cause male infertility and are associated with nonobstructive azoospermia in humans

Sun

Wen

et al. 2016

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

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Processing of pre-mRNA into mRNA is an important regulatory mechanism in eukaryotes that is mediated by the spliceosome, a huge and dynamic ribonucleoprotein complex. Splicing defects are implicated in a spectrum of human disease, but the underlying mechanistic links remain largely unresolved. Using a genome-wide association approach, we have recently identified single nucleotide polymorphisms in humans that associate with nonobstructive azoospermia (NOA), a common cause of male infertility. Here, using genetic manipulation of corresponding candidate loci in Drosophila, we show that the spliceosome component SNRPA1/U2A is essential for male fertility. Loss of U2A in germ cells of the Drosophila testis does not affect germline stem cells, but does result in the accumulation of mitotic spermatogonia that fail to differentiate into spermatocytes and mature sperm. Lack of U2A causes insufficient splicing of mRNAs required for the transition of germ cells from proliferation to differentiation. We show that germ cellspecific disruption of other components of the major spliceosome manifests with the same phenotype, demonstrating that mRNA processing is required for the differentiation of spermatogonia. This requirement is conserved, and expression of human SNRPA1 fully restores spermatogenesis in U2A mutant flies. We further report that several missense mutations in human SNRPA1 that inhibit the assembly of the major spliceosome dominantly disrupt spermatogonial differentiation in Drosophila. Collectively, our findings uncover a conserved and specific requirement for the major spliceosome during the transition from spermatogonial proliferation to differentiation in the male testis, suggesting that spliceosome defects affecting the differentiation of human spermatogonia contribute to NOA.

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“…USP26 gene, located on Xq26.2 region is expressed throughout the testes in the preliminary stages of spermatogenesis [11]. Any mutation in this gene results in the severe impairment of spermatogenesis [12]. Another gene DIAPH2 located at Xq22 region which affects spermatogenesis is disrupted due to deletion at Xq21.3.…”

Section: Discussionmentioning

confidence: 99%

Case Report on Xq Deletion - As a Cause for Primary Infertility in Male

Sharma

Sambyal²,

Kamboj

2016

Int J of Biomed & Adv Res

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Male infertility is often described in terms of role played by Y chromosome and Yq microdeletions. But studies have shown that X chromosome, being enriched for testis specific genes plays a significant role in formation of mature spermatozoa. The couple under study had undergone treatments for infertility including 7 Intrauterine inseminations (IUI) and 6 Invitro Fertilization (IVF) cycles but without any success. On cytogenetic analysis chromosomal aberrations were observed in both male and female partners. But male had more aberrations with major clonal aberrations in the form of Xq deletions. The genes CPXCR1, ARPT1, GLUD-2, SAGE-1 and USP26 are located on Xq21, Xq25 and Xq26 regions. These genes show testis specific expression pattern and play an important role in spermatogenesis. Therefore Xq deletions could be a cause for primary infertility in male.

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A comprehensive review of genetics and genetic testing in azoospermia

Cited by 155 publications

References 281 publications

Mutation in TDRD9 causes non-obstructive azoospermia in infertile men

Mutation in TDRD9 causes non-obstructive azoospermia in infertile men

Major spliceosome defects cause male infertility and are associated with nonobstructive azoospermia in humans

Case Report on Xq Deletion - As a Cause for Primary Infertility in Male

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