Quantitative proteomic biomarkers from extracellular vesicles of human seminal plasma in the differential diagnosis of azoospermia

Yao, Liping; Guo, Yueshuai; Zhang, Xiangzheng; Chen, Xu; Wang, Yichun; Liu, Xiaofei; Wang, Yue; Li, Yan; Qi, Yaling; Sha, Jiahao; Qin, Chao; Yang, Xiaoyu; Guo, Xuejiang

doi:10.1002/ctm2.423

Cited by 8 publications

(18 citation statements)

References 8 publications

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“…1 A). To further characterize the eIF5 loss-of-function assay, the eIF5 protein in Drosophila testes was analyzed by using a mass spectrometry (MS)-based targeted quantitative proteomic method in parallel reaction monitoring (PRM) mode [ 29 , 30 ]. Three different specific heavy peptides (LQDLTDGA K , SVTDIFY R , and VNTFIV K ) of eIF5 were synthesized and spiked into tryptic peptides of Drosophila testes.…”

Section: Resultsmentioning

confidence: 99%

Cyst stem cell lineage eIF5 non-autonomously prevents testicular germ cell tumor formation via eIF1A/eIF2γ-mediated pre-initiation complex

et al. 2022

Stem Cell Res Ther

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Background Stem cell niche maintains stem cell population identity and is essential for the homeostasis of self-renewal and differentiation in Drosophila testes. However, the mechanisms of CySC lineage signals-mediated soma–germline communications in response to external stimuli are unclear. Methods Pre-initiation complex functions were evaluated by UAS-Gal4-mediated cell effects. RNA sequencing was conducted in NC and eIF5 siRNA-treated cells. Genetic interaction analysis was used to indicate the relationships between eIF5 and eIF1A/eIF2γ in Drosophila testes. Results Here, we demonstrated that in CySCs, translation initiation factor eIF5 mediates cyst cell differentiation and the non-autonomously affected germ cell differentiation process. CySCs lacking eIF5 displayed unbalanced cell proliferation and apoptosis, forming testicular germ cell tumors (TGCTs) during spermatogenesis. eIF5 transcriptional regulation network analysis identified multiple metabolic processes and several key factors that might be involved in germ cell differentiation and TGCT formation. Importantly, knockdown of eIF1A and eIF2γ, key components of pre-initiation complex, mimicked the phenotype of knocking down eIF5 in the stem cell niche of Drosophila testes. Genetic interaction analysis indicated that eIF5 was sufficient to rescue the phenotype of tumorlike structures induced by down-regulating eIF1A or eIF2γ in CySCs. Conclusions These findings demonstrated that CySC lineage eIF5, together with eIF1A or eIF2γ, mediates soma–germline communications for the stem cell niche homeostasis in Drosophila testes, providing new insights for the prevention of TGCTs.

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Section: Resultsmentioning

confidence: 99%

Cyst stem cell lineage eIF5 non-autonomously prevents testicular germ cell tumor formation via eIF1A/eIF2γ-mediated pre-initiation complex

et al. 2022

Stem Cell Res Ther

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“…Testis-expressed protein 101 (TEX101) is a germ cell-specific GPI (glycosylphosphatidylinositol) anchored protein expressed on the plasma membrane of germ cells during all stages of spermatogenesis [61]. In total, TEX101 has been identified as a candidate biomarker for azoospermia in five comparative proteomic studies [28,37,38,48,60] and it has been one of the most validated biomarkers. Five independent studies validated the performance of TEX101 using several methods, starting with SID SRM [39,40], PRM-MS [60], and ELISA [41,42].…”

Section: Overview and Potential Clinical Application Of The Most Prom...mentioning

confidence: 99%

“…In total, TEX101 has been identified as a candidate biomarker for azoospermia in five comparative proteomic studies [28,37,38,48,60] and it has been one of the most validated biomarkers. Five independent studies validated the performance of TEX101 using several methods, starting with SID SRM [39,40], PRM-MS [60], and ELISA [41,42]. TEX101 has been shown to differentiate OA, NOA, and a PV man from fertile controls as well as have the potential for discrimination between OA and NOA.…”

Section: Overview and Potential Clinical Application Of The Most Prom...mentioning

confidence: 99%

“…It is involved in the glycolysis pathway of spermatozoa by activating phosphoglycerate-kinases, critical for the sperm motility process. It had been proposed as a biomarker for azoospermia diagnosis in terms of being able to differentiate both OA and NOA from controls as well as differentiate OA from NOA in a total of five comparative studies [26,37,38,48,60]. Its potential to discriminate fertile from azoospermia or PV man has also been validated in one study by Western blot and IHC [45].…”

Section: Detected In Allmentioning

confidence: 99%

“…L-lactate dehydrogenase C (LDHC) is another testis-enriched germcell-specific protein which as PGK2, is involved in the carbohydrate metabolic process affecting sperm motility [65]. LDHC has been shown to differentiate OA from controls and OA from NOA in four comparative proteomic studies [26,37,38,60]. Furthermore, it has been extensively validated using several methods such as Western blot and IHC [26,45], SID SRM [39,40] and PRM-MS [60].…”

Section: Detected In Allmentioning

confidence: 99%

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Proteomics of azoospermia: Towards the discovery of reliable markers for non‐invasive diagnosis

Rusevski

Plaseska‐Karanfilska

Davalieva

2022

Proteomics Clinical Apps

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Purpose: Azoospermia, as the most severe form of male infertility, no longer indicates sterility due to modern medical advancements. The current diagnostic procedure based on testicular biopsy has several drawbacks which urges the development of novel, non-invasive diagnostic procedures based on biomarkers. In the last two decades, there have been many proteomics studies investigating potential azoospermia biomarkers. In this review, we aimed to provide a critical evaluation of these studies.Experimental Design: Published articles were gathered by systematic literature search using Pubmed, Science Direct, and Google Scholar databases until March 2022 and were further preselected to include only studies on human samples.Results: A detailed review of these studies encompassed the proteomics platforms, sources of material, proposed candidate biomarkers, and their potential diagnostic specificity and sensitivity. In addition, emphasis was put on the top, most identified and validated biomarker candidates and their potential for discriminating azoospermia types and subtypes as well as predicting sperm retrieval success rate.Conclusions: Proteomics research of azoospermia has laid the groundwork for the development of a more streamlined biomarker testing. The future research should be focused on well-designed studies including samples from all types/subtypes as well as further testing of the most promising biomarkers identified so far.

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Comparative proteomics analysis of human FFPE testicular tissues reveals new candidate biomarkers for distinction among azoospermia types and subtypes

Davalieva

Rusevski

Velkov

et al. 2022

Journal of Proteomics

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Quantitative proteomic biomarkers from extracellular vesicles of human seminal plasma in the differential diagnosis of azoospermia

Cited by 8 publications

References 8 publications

Cyst stem cell lineage eIF5 non-autonomously prevents testicular germ cell tumor formation via eIF1A/eIF2γ-mediated pre-initiation complex

Cyst stem cell lineage eIF5 non-autonomously prevents testicular germ cell tumor formation via eIF1A/eIF2γ-mediated pre-initiation complex

Proteomics of azoospermia: Towards the discovery of reliable markers for non‐invasive diagnosis

Comparative proteomics analysis of human FFPE testicular tissues reveals new candidate biomarkers for distinction among azoospermia types and subtypes

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