Systematic Analysis of Protein Interaction Network Associated with Azoospermia

Sabetian, Soudabeh; Shamsir, Mohd Shahir

doi:10.3390/ijms17111857

Cited by 16 publications

(10 citation statements)

References 52 publications

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“…Apart from obvious GO terms for broad biological processes, such as spermatogenesis, spermatid development, etc, many other specific terms were also found to be enriched among the 3,000 down-regulated genes in the current study, which have also been reported earlier to be key processes associated with NOA (e.g., 11,43,44). Though there were many common observations among the functions and pathways over-represented among genes up-or down-regulated as per earlier studies, a few new observations were also noted.…”

Section: Discussionsupporting

confidence: 78%

Listing candidate diagnostic markers and transcriptomic exploration of the molecular basis of a type of male infertility (Non-Obstructive Azoospermia), via next generation sequencing methods

Govindkumar

Basavaraju

Bajpai³

et al. 2019

Preprint

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Studying the molecular basis of Non-Obstructive Azoospermia (NOA), a type of male infertility with failed spermatogenesis at various stages, can also help in exploring molecular basis of human spermatogenesis and possibly pave way to identify new targets for male contraceptive development. Hence, we initiated a functional genomics study by applying RNA-seq. Testicular biopsies collected from donors with Non-Obstructive Azoospermia (NOA), Obstructive Azoospermia (OA), Congenital Bilateral Absence of the Vas Deferens (CBAVD), and Varicocele (VA) conditions. Strong association of 100+ genes with human spermatogenesis and NOA has been detected via NGS-based transcriptomic analysis. In addition, 20 RNA molecules have been short-listed for potential diagnostic applications (non-obstructive azoospermia vs. obstructive azoospermia, varicocele or normal). A hierarchical list of several genes and alternatively spliced mRNAs, transcribed differentially in NOA, is reported -based on a 'strength of association'. Such association with NOA, spermatogenesis or both is a new finding for many genes as revealed by a comparison with a newly prepared comprehensive list of genes having such association with human spermatogenesis/NOA. Many top-ranking genes involved in viral gene expression were up-regulated in testes from NOA-patients, while those associated with an antiviral mechanism were down-regulated. A tangential finding: while most well-established control mRNAs did not qualify, two new ones worked best in RT-qPCR experiments. Needle-aspiration of testicular biopsies, followed by the use of short-listed promising candidate biomarkers (i.e., 16 mRNA & 4 chimeric transcripts) and control mRNAs in RT-qPCR-based diagnostic assays, may help to avoid open surgeries in future.

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Section: Discussionsupporting

confidence: 78%

Listing candidate diagnostic markers and transcriptomic exploration of the molecular basis of a type of male infertility (Non-Obstructive Azoospermia), via next generation sequencing methods

Govindkumar

Basavaraju

Bajpai³

et al. 2019

Preprint

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“…The CREBBP (CREB-binding protein) gene is related to transcriptional coactivation of different transcription factors and has been associated with azoospermia (Sabetian & Shamsir, 2016). Partial disruption of CREBBP gene in mice interferes in germ cell development at the spermatocyte stage (Hummler et al, 1994) because CREB-binding protein is required to produce a critical Sertoli cell-derived factor for germ cell survival (Scobey et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Genome‐wide association study for age at puberty in young Nelore bulls

Stafuzza

Silva

Silva³

et al. 2019

J Animal Breeding Genetics

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Selection for bulls that would reach puberty early reduces the generation interval and increases fertility and herd productivity. Despite its economic importance, there are few QTL associated with age at puberty described in the literature. In this study, a weighted single‐step genome‐wide association study was performed to detect genomic regions and putative candidate genes related to age at puberty in young Nelore bulls. Several protein‐coding genes related to spermatogenesis functions were identified within the genomic regions that explain more than 0.5% of the additive genetic variance for age at puberty in Nelore bulls, such as ADAM11, BRCA1, CSNK2A, CREBBP, MEIOC, NDRG2, NECTIN3, PARP2, PARP9, PRSS21, RAD51C, RNASE4, SLX4, SPA17, TEX14, TIMP2 and TRIP13 gene. Enrichment analysis by DAVID also revealed several GO terms related to spermatogenesis such as DNA replication (GO:0006260), male meiosis I (GO:0007141), double‐strand break repair (GO:0006302), base excision repair (GO:0006284), apoptotic process (GO:0006915), cell–cell adhesion (GO: 0098609) and focal adhesion (GO:0005925). The heritability for age at puberty shows that this trait can be improved based on traditional EBV selection. Adding genomic information to the system helps to elucidate genes and molecular mechanisms controlling the sexual precocity and could help to predict sexual precocity in Nelore bulls with greater accuracy at younger age, which would speed up the breeding programme for this breed.

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“…The FDR (false discovery rate) was set as <1% on both protein and peptide levels. The data were normalized across the conditions including the replicates using spectral counts method 40,41 . For identifying differentially expressed proteins, the normalized peptide matches of the treatment were divided by that of control conditions.…”

Section: Methodsmentioning

confidence: 99%

“…PPI information of proteins was obtained from the String database (version 9.1; http://string-db.org/) having the confidence score > 0.7. It was further imported in Cytoscape (version 3.6.0; http://www.cytoscape.org/) and the union calculation was performed, followed by removal of the duplicated edges by using Advanced Network Merge 40,42 .…”

Section: Methodsmentioning

confidence: 99%

Differential protein profiling of soil diazotroph Rhodococcus qingshengii S10107 towards low-temperature and nitrogen deficiency

Suyal

Juyal

Kumar

et al. 2019

Sci Rep

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Protein-based biomarkers can be a promising approach for identification and real-time monitoring of the bio-inoculants employed under sustainable agricultural plans. In this perspective, differential proteomics of psychrophilic diazotroph Rhodococcus qingshengii S10107 (JX173283) was performed to unravel its adaptive responses towards low-temperature nitrogen deficiency and identification of a biomarker for respective physiological conditions. LC-MS/MS-based proteome analysis mapped more than 4830 proteins including 77 up-regulated and 47 down-regulated proteins (p ≤ 0.05). Differential expression of the structural genes of nif regulon viz. nifH, nifD, and nifK along with their response regulators i.e. nifA, nifL, and nifB indicated that the nitrogenase complex was activated successfully. Besides up-regulating the biosynthesis of certain amino acids viz. Leucine, Lysine, and Alanine; the expression of the peptidoglycan synthesis proteins were also increased; while, the enzymes involved in Lipid biosynthesis were found to decrease. Furthermore, two important enzymes of the pentose phosphate pathway viz. Transketolase and Transaldolase along with Ribose import ATP-binding protein RbsA were also found to induce significantly under low temperature a nitrogen deficient condition, which suggests the cellular need for ample ribose sugar instantly. Additionally, comparative protein profiling of S10107 strain with our previous studies revealed that CowN protein was significantly up-regulated in all the cases under low-temperature nitrogen deficient conditions and therefore, can be developed as a biomarker. Conclusively, present study for the first time provides an in-depth proteome profiling of R. qingshengii S10107 and proclaims CowN as a potential protein biomarker for monitoring BNF under cold niches.

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Systematic Analysis of Protein Interaction Network Associated with Azoospermia

Cited by 16 publications

References 52 publications

Listing candidate diagnostic markers and transcriptomic exploration of the molecular basis of a type of male infertility (Non-Obstructive Azoospermia), via next generation sequencing methods

Listing candidate diagnostic markers and transcriptomic exploration of the molecular basis of a type of male infertility (Non-Obstructive Azoospermia), via next generation sequencing methods

Genome‐wide association study for age at puberty in young Nelore bulls

Differential protein profiling of soil diazotroph Rhodococcus qingshengii S10107 towards low-temperature and nitrogen deficiency

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