PRSS55 is a novel potential causative gene for human male infertility

Liu, Man; Jiang, Chuan; Zhang, Xueguang; Zhang, Guohui; Liu, Mohan; Zheng, Rui; Yang, Yihong; Shen, Ying

doi:10.1016/j.rbmo.2022.05.016

Cited by 2 publications

(2 citation statements)

References 19 publications

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“…Since sperm formation requires a particular energetic demand, the timely expression of PRSS55 seems to play a special role in the regulation of mitochondrial energy metabolism. In addition, a homozygous mutation in PRSS55 was recently found to be a potential cause of infertility in male patients [28]. Also, mitochondria-related dysregulations have been frequently detected in testicular germ cell tumor (TGCT) patients even with normal semen parameters [29].…”

Section: Discussionmentioning

confidence: 99%

PRSS55 Regulates Energy Homeostasis and BCAA Metabolism via Interacting with BCKDK in Mouse Testes and Sperm

Ge,

Shen,

Xiong

et al. 2024

Preprint

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Previous studies have shown that PRSS55 is required for male fertility in mice, and potentially in humans, and is involved in energy metabolism in mouse sperm. However, the underline mechanism remains unclear. Here we show that Prss55 deficiency leads to significant changes in protein levels identified by DIA-based mass spectrometry proteomics in enriched PRSS55-expressing testicular cells and caudal epididymal sperm as compared to wt mice. Bioinformatic assessments reveal that the majority of differentially expressed proteins (DEPs) were significantly enriched in the branched-chain amino acids (BCAA) degradation pathway and the oxidative phosphorylation (OXPHOS) process. Accumulation of isoleucine and leucine was identified in Prss55-/- mice by untargeted metabolomics. We also observe significantly downregulated IVD and NDUFB8 protein levels, impaired in adenosine triphosphate (ATP) production, abnormal NAD+/NADH ratio, and decreased mitochondrial membrane potential in knockout models. Secondly, co-immunoprecipitation/mass spectrometry (Co-IP/MS) by using V5-PRSS55 knock-in mice and in vitro Co-IP assays suggested that PRSS55 interacts with mitochondrial protein BCKDK, which is involved in BCAA metabolism. Overexpressed PRSS55 was found to be enriched in mitochondria by immunofluorescence and immunoblotting assays. All these data demonstrate that PRSS55 regulates energy homeostasis and BCAAs metabolism in testes and sperm of mice, implicating a potential mechanism of male infertility in mice lacking PRSS55 and in human due to PRSS55 mutation.

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Section: Discussionmentioning

confidence: 99%

PRSS55 Regulates Energy Homeostasis and BCAA Metabolism via Interacting with BCKDK in Mouse Testes and Sperm

Ge,

Shen,

Xiong

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…Despite being relatively understudied, Prss55 is an important enzyme molecule, and its specific function and mechanism of action remain unknown. Nevertheless, emerging research suggests a potential association between Prss55 and the reproductive system ( 51 , 52 ). In our study, utilizing Prss55-GSEA, we have identified its potential involvement in crucial biological processes such as angiogenesis and developmental regulation, myocardial tissue development, myocardial contraction, and cardiomyocyte development.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic potential of energy metabolism-related genes in heart failure with preserved ejection fraction

Gou,

Zhao,

Dong

et al. 2023

Front. Endocrinol.

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BackgroundHeart failure with preserved ejection fraction (HFpEF) is associated with changes in cardiac metabolism that affect energy supply in the heart. However, there is limited research on energy metabolism-related genes (EMRGs) in HFpEF.MethodsThe HFpEF mouse dataset (GSE180065, containing heart tissues from 10 HFpEF and five control samples) was sourced from the Gene Expression Omnibus database. Gene expression profiles in HFpEF and control groups were compared to identify differentially expressed EMRGs (DE-EMRGs), and the diagnostic biomarkers with diagnostic value were screened using machine learning algorithms. Meanwhile, we constructed a biomarker-based nomogram model for its predictive power, and functionality of diagnostic biomarkers were conducted using single-gene gene set enrichment analysis, drug prediction, and regulatory network analysis. Additionally, consensus clustering analysis based on the expression of diagnostic biomarkers was utilized to identify differential HFpEF-related genes (HFpEF-RGs). Immune microenvironment analysis in HFpEF and subtypes were performed for analyzing correlations between immune cells and diagnostic biomarkers as well as HFpEF-RGs. Finally, qRT-PCR analysis on the HFpEF mouse model was used to validate the expression levels of diagnostic biomarkers.ResultsWe selected 5 biomarkers (Chrna2, Gnb3, Gng7, Ddit4l, and Prss55) that showed excellent diagnostic performance. The nomogram model we constructed demonstrated high predictive power. Single-gene gene set enrichment analysis revealed enrichment in aerobic respiration and energy derivation. Further, various miRNAs and TFs were predicted by Gng7, such as Gng7-mmu-miR-6921-5p, ETS1-Gng7. A lot of potential therapeutic targets were predicted as well. Consensus clustering identified two distinct subtypes of HFpEF. Functional enrichment analysis highlighted the involvement of DEGs-cluster in protein amino acid modification and so on. Additionally, we identified five HFpEF-RGs (Kcnt1, Acot1, Kcnc4, Scn3a, and Gpam). Immune analysis revealed correlations between Macrophage M2, T cell CD4+ Th1 and diagnostic biomarkers, as well as an association between Macrophage and HFpEF-RGs. We further validated the expression trends of the selected biomarkers through experimental validation.ConclusionOur study identified 5 diagnostic biomarkers and provided insights into the prediction and treatment of HFpEF through drug predictions and network analysis. These findings contribute to a better understanding of HFpEF and may guide future research and therapy development.

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PRSS55 is a novel potential causative gene for human male infertility

Cited by 2 publications

References 19 publications

PRSS55 Regulates Energy Homeostasis and BCAA Metabolism via Interacting with BCKDK in Mouse Testes and Sperm

PRSS55 Regulates Energy Homeostasis and BCAA Metabolism via Interacting with BCKDK in Mouse Testes and Sperm

Diagnostic potential of energy metabolism-related genes in heart failure with preserved ejection fraction

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