Coding and regulatory transcriptome comparisons between fertile and infertile spermatozoa identify
            <scp>RNA</scp>
            signatures of male infertility

Joshi, Meghali; Andrabi, Syed Waseem; Singh, Vertika; Makker, Girish Chandra; Mishra, Geetanjali; Gupta, Gopal; Rajender, Singh

doi:10.1111/and.14437

Cited by 8 publications

(7 citation statements)

References 55 publications

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“…High cost of analysis, critical role of RNA preparation quality and relatively narrow range of variation in their expression are some of the limitations of using miRNAs as biomarkers of infertility. It is noteworthy that all studies on sperm miRNA in infertility, except our study [31], were microarray or RT-PCR based, next generation sequencing based studies would identify as yet unidentified miRNAs in sperm.…”

Section: Discussionmentioning

confidence: 92%

“…On comparison of miRNA differential expression data across all published studies, including our case-control sequencing data [31], we found 497 differentially expressed miRNAs (DE-miRNAs) in sperm/semen of infertile patients as compared to fertile controls. Consistent differential expression of seven miRNAs across diverse studies indicated their strong association with infertility, suggesting their potential as markers of sperm fertility/quality.…”

Section: Discussionmentioning

confidence: 99%

“…Eight studies (two microarray and six RT-PCR based) had investigated the expression of miRNAs in sperm/semen of infertile patients till date (Table 1). We also included our miRNA sequencing data for oligo/oligoasthenozospermia infertile Indian patients [31]. Thus, nine datasets were compared to identify common differentially expressed miRNAs in male infertility.…”

Section: Literature Searchmentioning

confidence: 99%

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Qualitative and quantitative assessment of sperm miRNAs identifies hsa-miR-9-3p, hsa-miR-30b-5p and hsa-miR-122-5p as potential biomarkers of male infertility and sperm quality

Joshi

Andrabi

Yadav

et al. 2022

Reprod Biol Endocrinol

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Background In contrast with the preceding stages of the germ cells, spermatozoa are unusually rich in small non-coding RNAs in comparison to the coding RNAs. These small RNAs may have had an essential role in the process of spermatogenesis or may have critical roles in the post-fertilization development. Sporadic efforts have identified a few differentially expressed miRNAs in infertile individuals, which do not replicate in other studies. Methods In order to identify miRNAs signatures of infertility or poor sperm quality, we compared miRNA differential expression data across nine datasets, followed by their analysis by real-time PCR in a case–control study. This was followed by the validation of potential biomarkers in yet another set of cases and controls. For this, total RNA was isolated from 161 sperm samples. miRNA expression levels in infertile cases and fertile controls were measured using TaqMan real-time PCR. Meta-analyses of two miRNAs (hsa-miR-9-3p and hsa-miR-122-5p) were performed using Comprehensive Meta‐Analysis Software (version 2). All statistical analyses were performed with the help of GraphPad Prism Software (version 8). Results Literature search identified seven miRNAs (hsa-let-7a-5p, hsa-miR-9-3p, hsa-miR-22-5p, has-miR-30b-5p, hsa-miR-103-3p, hsa-miR-122-5p and hsa-miR-335-5p) showing consistent dysregulation in infertility across a minimum of four studies. In the discovery phase, six miRNAs showed strong association with infertility with four (hsa-miR-9-3p, hsa-miR-30b-5p, hsa-miR-103-3p and hsa-miR-122-5p) showing consistent differential regulation across all sub-groups. Receiver operating characteristic (ROC) curve analysis showed that the area under curve of > 0.75 was achieved by three (hsa-mir-9-3p, hsa-miR-30b-5p and hsa-miR-122-5p) miRNAs. In the validation phase, these three miRNAs showed consistent association with infertility (hsa-mir-9-3p, hsa-miR-30b-5p, and hsa-miR-122-5p). Meta-analysis on hsa-miR-122-5p showed its significant quantitative association with infertility [Hedge’s g = -2.428, p = 0.001 (Random effects)]. Conclusions Three miRNAs (hsa-miR-9-3p, hsa-miR-30b-5p and hsa-miR-122-5p) have strong linkage with infertility and a high potential as sperm quality biomarkers.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Literature Searchmentioning

confidence: 99%

See 1 more Smart Citation

Qualitative and quantitative assessment of sperm miRNAs identifies hsa-miR-9-3p, hsa-miR-30b-5p and hsa-miR-122-5p as potential biomarkers of male infertility and sperm quality

Joshi

Andrabi

Yadav

et al. 2022

Reprod Biol Endocrinol

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“…The problem of sample size has always been an objective problem in related research of human gametes. For example, some sperm proteomics studies can only detect single-digit samples [76,77], and sperm transcriptome analysis also has objective limitations.…”

Section: Limitation Of the Studymentioning

confidence: 99%

Epigenetic Alterations in Cryopreserved Human Spermatozoa: Suspected Potential Functional Defects

Wang

Todorov

Cheng

et al. 2022

Cells

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Background: Gene set enrichment analysis (GSEA) was conducted on raw data, and alternative splicing (AS) events were found after mRNA sequencing of human spermatozoa. In this study, we aimed to compare unknown micro-epigenetics alternations in fresh and cryopreserved spermatozoa to evaluate the effectivity of cryopreservation protocols. Methods: Spermatozoa were divided into three groups: fresh spermatozoa (group 1), cryoprotectant-free vitrified spermatozoa (group 2), and conventionally frozen spermatozoa (group 3). Nine RNA samples (three replicates in each group) were detected and were used for library preparation with an Illumina compatible kit and sequencing by the Illumina platform. Results: Three Gene Ontology (GO) terms were found to be enriched in vitrified spermatozoa compared with fresh spermatozoa: mitochondrial tRNA aminoacylation, ATP-dependent microtubule motor activity, and male meiotic nuclear division. In alternative splicing analysis, a number of unknown AS events were found, including functional gene exon skipping (SE), alternative 5′ splice sites (A5SS), alternative 3′ splice sites (A3SS), mutually exclusive exon (MXE), and retained intron (RI). Conclusions: Cryopreservation of spermatozoa from some patients can agitate epigenetic instability, including increased alternative splicing events and changes in crucial mitochondrial functional activities. For fertilization of oocytes, for such patients, it is recommended to use fresh spermatozoa whenever possible; cryopreservation of sperm is recommended to be used only in uncontested situations.

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“…These studies showed a direct link between the messenger RNAs (mRNAs) and different classes of non-coding RNAs such as microRNAs (miRNAs) in men undergoing infertility treatment. As for the more holistic approaches, a total of 60,505 transcripts have been identified for the sperm transcriptome including 11,688 differentially expressed transcripts in infertile and fertile men (2022) [ 6 ]. A total of 6871 proteins have been identified for the sperm proteome, as reviewed by [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Proteomic Landscape of Human Sperm in Patients with Different Spermatogenic Impairments

Becker

Smadi

Räschle

et al. 2023

Cells

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Although the proteome of sperm has been characterized, there is still a lack of high-throughput studies on dysregulated proteins in sperm from subfertile men, with only a few studies on the sperm proteome in asthenozoospermic and oligoasthenozoospermic men. Using liquid chromatography–mass spectrometry (LC-MS/MS) along with bioinformatics analyses, we investigated the proteomic landscape of sperm collected from subfertile men (n = 22), i.e., asthenozoospermic men (n = 13), oligoasthenozoospermic men (n = 9) and normozoospermic controls (n = 31). We identified 4412 proteins in human sperm. Out of these, 1336 differentially abundant proteins were identified in 70% of the samples. In subfertile men, 32 proteins showed a lower abundance level and 34 showed a higher abundance level when compared with normozoospermic men. Compared to normozoospermic controls, 95 and 8 proteins showed a lower abundance level, and 86 and 1 proteins showed a higher abundance level in asthenozoospermic and oligoasthenozoospermic men, respectively. Sperm motility and count were negatively correlated with 13 and 35 and positively correlated with 37 and 20 differentially abundant proteins in asthenozoospermic and oligoasthenozoospermic men, respectively. The combination of the proteins APCS, APOE, and FLOT1 discriminates subfertile males from normozoospermic controls with an AUC value of 0.95. Combined APOE and FN1 proteins discriminate asthenozoospermic men form controls with an AUC of 1, and combined RUVBL1 and TFKC oligoasthenozoospermic men with an AUC of 0.93. Using a proteomic approach, we revealed the proteomic landscape of sperm collected from asthenozoospermic or oligoasthenozoospermic men. Identified abundance changes of several specific proteins are likely to impact sperm function leading to subfertility. The data also provide evidence for the usefulness of specific proteins or protein combinations to support future diagnosis of male subfertility.

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Coding and regulatory transcriptome comparisons between fertile and infertile spermatozoa identify RNA signatures of male infertility

Cited by 8 publications

References 55 publications

Qualitative and quantitative assessment of sperm miRNAs identifies hsa-miR-9-3p, hsa-miR-30b-5p and hsa-miR-122-5p as potential biomarkers of male infertility and sperm quality

Qualitative and quantitative assessment of sperm miRNAs identifies hsa-miR-9-3p, hsa-miR-30b-5p and hsa-miR-122-5p as potential biomarkers of male infertility and sperm quality

Epigenetic Alterations in Cryopreserved Human Spermatozoa: Suspected Potential Functional Defects

Proteomic Landscape of Human Sperm in Patients with Different Spermatogenic Impairments

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