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Transcriptomic analysis of the Non-Obstructive Azoospermia (NOA) to address gene expression regulation in human testis

Overview of attention for article published in Spermatogenesis, March 2023
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About this Attention Score

  • Above-average Attention Score compared to outputs of the same age (55th percentile)
  • High Attention Score compared to outputs of the same age and source (80th percentile)

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Title
Transcriptomic analysis of the Non-Obstructive Azoospermia (NOA) to address gene expression regulation in human testis
Published in
Spermatogenesis, March 2023
DOI 10.1080/19396368.2023.2176268
Pubmed ID
Authors

Govindkumar Balagannavar, Kavyashree Basavaraju, Akhilesh Kumar Bajpai, Sravanthi Davuluri, Shruthi Kannan, Vasan S. Srini, Darshan S. Chandrashekar, Neelima Chitturi, Kshitish K. Acharya

Abstract

There is a need to understand the molecular basis of testes under Non-Obstructive Azoospermia (NOA), a state of failed spermatogenesis. There has been a lack of attention to the transcriptome at the level of alternatively spliced mRNAs (iso-mRNAs) and the mechanism of gene expression regulation. Hence, we aimed to establish a reliable iso-mRNA profile of NOA-testes, and explore molecular mechanisms - especially those related to gene expression regulation. We sequenced mRNAs from testicular samples of donors with complete spermatogenesis (control samples) and a failure of spermatogenesis (NOA samples). We identified differentially expressed genes and their iso-mRNAs via standard NGS data analyses. We then listed these iso-mRNAs hierarchically based on the extent of consistency of differential quantities across samples and groups, and validated the lists via RT-qPCRs (for 80 iso-mRNAs). In addition, we performed extensive bioinformatic analysis of the splicing features, domains, interactions, and functions of differentially expressed genes and iso-mRNAs. Many top-ranking down-regulated genes and iso-mRNAs, i.e., those down-regulated more consistently across the NOA samples, are associated with mitosis, replication, meiosis, cilium, RNA regulation, and post-translational modifications such as ubiquitination and phosphorylation. Most down-regulated iso-mRNAs correspond to full-length proteins that include all expected domains. The predominance of alternative promoters and termination sites in these iso-mRNAs indicate their gene expression regulation via promoters and UTRs. We compiled a new, comprehensive list of human transcription factors (TFs) and used it to identify TF-'TF gene' interactions with potential significance in down-regulating genes under the NOA condition. The results indicate that RAD51 suppression by HSF4 prevents SP1-activation, and SP1, in turn, could regulate multiple TF genes. This potential regulatory axis and other TF interactions identified in this study could explain the down-regulation of multiple genes in NOA-testes. Such molecular interactions may also have key regulatory roles during normal human spermatogenesis.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 9 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 9 100%

Demographic breakdown

Readers by professional status Count As %
Unspecified 2 22%
Researcher 1 11%
Other 1 11%
Unknown 5 56%
Readers by discipline Count As %
Unspecified 2 22%
Biochemistry, Genetics and Molecular Biology 1 11%
Medicine and Dentistry 1 11%
Unknown 5 56%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 18 March 2023.
All research outputs
#15,441,303
of 26,171,302 outputs
Outputs from Spermatogenesis
#293
of 540 outputs
Outputs of similar age
#188,625
of 430,851 outputs
Outputs of similar age from Spermatogenesis
#2
of 10 outputs
Altmetric has tracked 26,171,302 research outputs across all sources so far. This one is in the 40th percentile – i.e., 40% of other outputs scored the same or lower than it.
So far Altmetric has tracked 540 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.6. This one is in the 45th percentile – i.e., 45% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 430,851 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 55% of its contemporaries.
We're also able to compare this research output to 10 others from the same source and published within six weeks on either side of this one. This one has scored higher than 8 of them.