Proteomic Landscape of Human Sperm in Patients with Different Spermatogenic Impairments

Becker, Lea Simone; Smadi, Mohammad A. Al; Räschle, Markus; Rishik, Shusruto; Abdul‐Khaliq, Hashim; Meese, Eckart; Abu‐Halima, Masood

doi:10.3390/cells12071017

Cited by 5 publications

(3 citation statements)

References 71 publications

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“…However, the implication of its downregulation remains elusive despite its role in tail-associated functions and sperm motility (Malm et al, 2008). It was observed to be downregulated in another proteomic study comparing the proteomic landscape of sub-fertile men with different sperm abnormalities (Becker et al, 2023). The downregulation of these proteins was also observed in both waves, indicating the effect of COVID-19 on spermatogenesis.…”

Section: Discussionmentioning

confidence: 99%

Semen proteomics reveals alterations in fertility-related proteins post-recovery from COVID-19

Dash,

Salkar,

Nissa

et al. 2023

Front. Physiol.

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Introduction: Changes to sperm quality and decline in reproductive function have been reported in COVID-19-recovered males. Further, the emergence of SARS-CoV-2 variants has caused the resurgences of COVID-19 cases globally during the last 2 years. These variants show increased infectivity and transmission along with immune escape mechanisms, which threaten the already burdened healthcare system. However, whether COVID-19 variants induce an effect on the male reproductive system even after recovery remains elusive.Methods: We used mass-spectrometry-based proteomics approaches to understand the post-COVID-19 effect on reproductive health in men using semen samples post-recovery from COVID-19. The samples were collected between late 2020 (1st wave, n = 20), and early-to-mid 2021 (2nd wave, n = 21); control samples were included (n = 10). During the 1st wave alpha variant was prevalent in India, whereas the delta variant dominated the second wave.Results: On comparing the COVID-19-recovered patients from the two waves with control samples, using one-way ANOVA, we identified 69 significantly dysregulated proteins among the three groups. Indeed, this was also reflected by the changes in sperm count, morphology, and motility of the COVID-19- recovered patients. In addition, the pathway enrichment analysis showed that the regulated exocytosis, neutrophil degranulation, antibacterial immune response, spermatogenesis, spermatid development, regulation of extracellular matrix organization, regulation of peptidase activity, and regulations of calcium ion transport were significantly dysregulated. These pathways directly or indirectly affect sperm parameters and function. Our study provides a comprehensive landscape of expression trends of semen proteins related to male fertility in men recovering from COVID-19.Discussion: Our study suggests that the effect of COVID-19 on the male reproductive system persists even after recovery from COVID-19. In addition, these post-COVID-19 complications persist irrespective of the prevalent variants or vaccination status.

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Section: Discussionmentioning

confidence: 99%

Semen proteomics reveals alterations in fertility-related proteins post-recovery from COVID-19

Dash,

Salkar,

Nissa

et al. 2023

Front. Physiol.

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“…We recently conducted a study of the proteomic landscape of human sperm obtained from oligoasthenozoospermic men, comparing these samples with samples from normozoospermic men using LC-MS/MS. Despite the detection of 4412 proteins and the analysis of 53 samples, we did not detect any of the miRNA-23a/b targets [ 38 ]. In the present study, we performed Western blot that also failed to detect the proteins that are encoded by the miRNA-23a/b target genes (Anti-NOL4, PA5-103986, Invitrogen and Anti-SOX6, ab64946, Abcam).…”

Section: Discussionmentioning

confidence: 99%

Towards a More Comprehensive Picture of the MicroRNA-23a/b-3p Impact on Impaired Male Fertility

Becker

Smadi

Koch

et al. 2023

Biology

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The expression levels of various genes involved in human spermatogenesis are influenced by microRNAs (miRNAs), specifically microRNA-23a/b-3p. While certain genes are essential for spermatogenesis and male germ cell function, the regulation of their expression remains unclear. This study aimed to investigate whether microRNA-23a/b-3p targets genes involved in spermatogenesis and the impact of this targeting on the expression levels of these genes in males with impaired fertility. In-silico prediction and dual-luciferase assays were used to determine the potential connections between microRNA-23a/b-3p overexpression and reduced expression levels of 16 target genes. Reverse transcription-quantitative PCR (RT-qPCR) was conducted on 41 oligoasthenozoospermic men receiving infertility treatment and 41 age-matched normozoospermic individuals to verify the lower expression level of target genes. By employing dual-luciferase assays, microRNA-23a-3p was found to directly target eight genes, namely NOL4, SOX6, GOLGA6C, PCDHA9, G2E3, ZNF695, CEP41, and RGPD1, while microRNA-23b-3p directly targeted three genes, namely SOX6, GOLGA6C, and ZNF695. The intentional alteration of the microRNA-23a/b binding site within the 3′ untranslated regions (3′UTRs) of the eight genes resulted in the loss of responsiveness to microRNA-23a/b-3p. This confirmed that NOL4, SOX6, GOLGA6C, PCDHA9, and CEP41 are direct targets for microRNA-23a-3p, while NOL4, SOX6, and PCDHA9 are direct targets for microRNA-23b-3p. The sperm samples of oligoasthenozoospermic men had lower expression levels of target genes than age-matched normozoospermic men. Correlation analysis indicated a positive correlation between basic semen parameters and lower expression levels of target genes. The study suggests that microRNA-23a/b-3p plays a significant role in spermatogenesis by controlling the expression of target genes linked to males with impaired fertility and has an impact on basic semen parameters.

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“…An independent set of sperm samples was collected from the men with oligoasthenozoospermia (n = 7) and normozoospermic controls (n = 7) to identify proteins with altered expression levels. These samples were analyzed along with another set to study the pro-tein landscape in human sperm (PXD033749) [22]. During LC-MS/MS processing, one sample from the oligoasthenozoospermia group was lost and subsequently excluded from further protein statistical analyses.…”

Section: Differentially Expressed Proteins In Sperm (Determined Using...mentioning

confidence: 99%

Sperm Motility Annotated Genes: Are They Associated with Impaired Fecundity?

Abu‐Halima

Becker

Smadi

et al. 2023

Cells

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Sperm motility is a prerequisite for achieving pregnancy, and alterations in sperm motility, along with sperm count and morphology, are commonly observed in subfertile men. The aim of the study was to determine whether the expression level of genes annotated with the Gene Ontology (GO) term ‘sperm motility’ differed in sperm collected from healthy men and men diagnosed with oligoasthenozoospermia. Reverse transcription quantitative real-time PCR (RT-qPCR), quantitative mass spectrometry (LC-MS/MS), and enrichment analyses were used to validate a set of 132 genes in 198 men present at an infertility clinic. Out of the 132 studied sperm-motility-associated genes, 114 showed differentially expressed levels in oligoasthenozoospermic men compared to those of normozoospermic controls using an RT-qPCR analysis. Of these, 94 genes showed a significantly lower expression level, and 20 genes showed a significantly higher expression level. An MS analysis of sperm from an independent cohort of healthy and subfertile men identified 692 differentially expressed proteins, of which 512 were significantly lower and 180 were significantly higher in oligoasthenozoospermic men compared to those of the normozoospermic controls. Of the 58 gene products quantified with both techniques, 48 (82.75%) showed concordant regulation. Besides the sperm-motility-associated proteins, the unbiased proteomics approach uncovered several novel proteins whose expression levels were specifically altered in abnormal sperm samples. Among these deregulated proteins, there was a clear overrepresentation of annotation terms related to sperm integrity, the cytoskeleton, and energy-related metabolism, as well as human phenotypes related to spermatogenesis and sperm-related abnormalities. These findings suggest that many of these proteins may serve as diagnostic markers of male infertility. Our study reveals an extended number of sperm-motility-associated genes with altered expression levels in the sperm of men with oligoasthenozoospermia. These genes and/or proteins can be used in the future for better assessments of male factor infertility.

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Proteomic Landscape of Human Sperm in Patients with Different Spermatogenic Impairments

Cited by 5 publications

References 71 publications

Semen proteomics reveals alterations in fertility-related proteins post-recovery from COVID-19

Semen proteomics reveals alterations in fertility-related proteins post-recovery from COVID-19

Towards a More Comprehensive Picture of the MicroRNA-23a/b-3p Impact on Impaired Male Fertility

Sperm Motility Annotated Genes: Are They Associated with Impaired Fecundity?

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