Sperm mitochondria dysfunction in response to testicular cancer

Qasemi, Maryam; Sur, Vishma Pratap; Simonik, Ondrej; Postlerova, Pavla; Skrobanek, Pavel; Hradec, Tomas; Boublikova, Ludmila; Zamecnik, Libor; Buchler, Tomas; Neuzil, Jiri; Komrskova, Katerina

doi:10.1111/eci.14146

Cited by 4 publications

(1 citation statement)

References 96 publications

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“…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]. PRSS55 may serve as a potential biomarker reflecting sperm mitochondrial functionality in testicular cancer patients, which may be beneficial in optimizing fertility management strategies.…”

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

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Bioenergetics of human spermatozoa in patients with testicular germ cell tumour

Simonik,

Bryndova,

Sur

et al. 2024

Preprint

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In testicular germ cell tumour (TGCT) patients, sperm cryopreservation prior to anti-cancer treatment represents the main fertility preservation approach. However, it is associated with low sperm recovery rate after thawing. Since sperm is a high-energy demanding cell, which is supplied by glycolysis and oxidative phosphorylation (OXPHOS), mitochondrial dysfunctionality can directly result in sperm anomalies. In this study, we investigated the bioenergetic pattern of cryopreserved sperm of TGCT patients in comparison with normozoospermic samples using two state-of-the-art methods; the Extracellular Flux Analyzer (XF Analyzer) and Two-Photon Fluorescence Lifetime imaging (2P-FLIM), in order to assess the contributions of OXPHOS and glycolysis to energy provision. A novel combined protocol for combined measurement of OXPHOS (Oxygen Consumption Rate – OCR) and glycolysis (Extracellular Acidification Rate – ECAR) using the XF Analyzer was developed together with a unique customized AI-based approach for semiautomated processing of 2P-FLIM images. Our study delivers optimized Low-HEPES modified Human Tubal Fluid media (mHTF) for sperm handling during pre-analytical and analytical phases to maintain sperm physiological parameters and optimal OCR, equivalent of OXPHOS. The negative effect of cryopreservation was signified by deterioration of both bioenergetic pathways represented by modified OCR and ECAR curves and the derived parameters. This was true for normozoospermic as well as TGCT samples, which showed even a stronger damage within the respiratory chain compared to the level of glycolytic activity impairment. These data are supported by 2P-FLIM analysis showing a significantly decreased bound NADH in contrast to unbound NAD(P)H which reflects decreased metabolic activity in samples from TGCT patients. Our study provides novel insight into the impact of TGCT on sperm bioenergetics and delivers a verified protocol to be used for assessment of human sperm metabolic activity, which can be a valuable tool for further research and clinical andrology.

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Abnormal Expression of COX5B Gene and Disorder of Mitochondrial Function in Cryptorchid Rats

Wang,

Miao,

et al. 2024

J Cellular Molecular Medi

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Cryptorchidism is one of the most common congenital malformations in the paediatric genitourinary tract. Data analysis of cryptorchidism‐related datasets in the GEO database and gene sequencing results from our institution, along with bioinformatic analysis of the merged mitochondrial gene datasets, revealed that COX5B is differentially expressed in the testes of children with cryptorchidism. Its encoded protein has attracted our attention as a key component of the mitochondrial respiratory chain complex IV. This study aims to explore the COX5B gene expression changes and related mitochondrial issues in cryptorchid rats. For this purpose, we established a cryptorchid rat model by surgery and used molecular biology and biochemistry techniques to detect and analyse the expression level of the COX5B gene and mitochondrial function indexes. The results indicated a significant decrease in COX5B gene expression in the affected testis of cryptorchid rats. The knockdown of COX5B expression in TM3 cells could be observed as the aggravation of cellular senescence, which led to the reduction of proliferation, as well as accompanied by the obvious disorders of mitochondrial function, including the increase of ROS and the decrease of ATP, in which MMP was significantly reduced. This suggests that the COX5B gene may play an important role in cryptorchid testis‐induced reproductive system damage and may be a new target for small molecule‐targeted therapy.

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Sperm mitochondria dysfunction in response to testicular cancer

Cited by 4 publications

References 96 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

Bioenergetics of human spermatozoa in patients with testicular germ cell tumour

Abnormal Expression of COX5B Gene and Disorder of Mitochondrial Function in Cryptorchid Rats

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