The combined human sperm proteome: cellular pathways and implications for basic and clinical science

Amaral, Alexandra; Castillo, Judit; Ramalho‐Santos, João; Oliva, Rafael

doi:10.1093/humupd/dmt046

Cited by 229 publications

(230 citation statements)

References 245 publications

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“…The use of genomic, transcriptomic and proteomic technologies significantly contributed to characterize and better understand the human sperm at the molecular level (Jodar et al, 2012;Kovac et al, 2013;Amaral et al, 2014a). However, metabolomics, the study of small and low molecular weight molecules that are products of metabolism, has not been greatly applied in the study and characterization of human sperm cells (Kovac et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…The identification of the metabolites and proteins as main determinants of the expression of the genomes and transcriptomes as also influenced by environmental cues, represents a first step to understand the normal composition and physiology of cells and tissues and their dysfunction associated with pathological states (Jodar et al, 2012;Wishart et al, 2013;Castillo et al, 2014a,b). In the case of the human spermatozoon, over 6000 proteins have been identified using mass spectrometry (MS), representing about 80% of the estimated proteome of this cell (Oliva et al, , 2009Amaral et al, 2013Amaral et al, , 2014aBaker et al, 2013;Azpiazu et al, 2014). However, and in *Correction added on 26 May 2015, after first online publication: article title corrected.…”

Section: Introductionmentioning

confidence: 99%

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Identification of endogenous metabolites in human sperm cells using proton nuclear magnetic resonance (¹H-NMR) spectroscopy and gas chromatography-mass spectrometry (GC-MS)

et al. 2015

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SUMMARYThe objective of this study was to contribute to the first comprehensive metabolomic characterization of the human sperm cell through the application of two untargeted platforms based on proton nuclear magnetic resonance ( 1 H-NMR) spectroscopy and gas chromatography coupled to mass spectrometry (GC-MS). Using these two complementary strategies, we were able to identify a total of 69 metabolites, of which 42 were identified using NMR, 27 using GC-MS and 4 by both techniques. The identity of some of these metabolites was further confirmed by two-dimensional C heteronuclear single-quantum correlation (HSQC) spectroscopy. Most of the metabolites identified are reported here for the first time in mature human spermatozoa. The relationship between the metabolites identified and the previously reported sperm proteome was also explored. Interestingly, overrepresented pathways included not only the metabolism of carbohydrates, but also of lipids and lipoproteins. Of note, a large number of the metabolites identified belonged to the amino acids, peptides and analogues super class. The identification of this initial set of metabolites represents an important first step to further study their function in male gamete physiology and to explore potential reasons for dysfunction in future studies. We also demonstrate that the application of NMR and MS provides complementary results, thus constituting a promising strategy towards the completion of the human sperm cell metabolome.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of endogenous metabolites in human sperm cells using proton nuclear magnetic resonance (¹H-NMR) spectroscopy and gas chromatography-mass spectrometry (GC-MS)

et al. 2015

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“…The defects leading to asthenozoospermia are not understood, which needs to change, to allow for innovative treatment options directed at the root cause of this problem. Mature sperm are believed to be transcriptionally and translationally silent (1), which demands proteomic studies (as opposed to genomic or transcriptomic studies) to understand the underlying pathways giving rise to sperm motility.…”

mentioning

confidence: 99%

Human Spermatozoa Quantitative Proteomic Signature Classifies Normo- and Asthenozoospermia

Saraswat

Joenväära

Jain

et al. 2017

Molecular & Cellular Proteomics

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Scarcely understood defects lead to asthenozoospermia, which results in poor fertility outcomes. Incomplete knowledge of these defects hinders the development of new therapies and reliance on interventional therapies, such as in vitro fertilization, increases. Sperm cells, being transcriptionally and translationally silent, necessitate the proteomic approach to study the sperm function. We have performed a differential proteomics analysis of human sperm and seminal plasma and identified and quantified 667 proteins in sperm and 429 proteins in seminal plasma data set, which were used for further analysis. Statistical and mathematical analysis combined with pathway analysis and self-organizing maps clustering and correlation was performed on the data set.It was found that sperm proteomic signature combined with statistical analysis as opposed to the seminal plasma proteomic signature can differentiate the normozoospermic versus the asthenozoospermic sperm samples. This is despite the results that some of the seminal plasma proteins have big fold changes among classes but they fall short of statistical significance. S-Plot of the sperm proteomic data set generated some high confidence targets, which might be implicated in sperm motility pathways. These proteins also had the area under the curve value of 0.9 or 1 in ROC curve analysis.Various pathways were either enriched in these proteomic data sets by pathway analysis or they were searched by their constituent proteins. Some of these pathways were axoneme activation and focal adhesion assembly, glycolysis, gluconeogenesis, cellular response to stress and nucleosome assembly among others. The mass spectrometric data is available via ProteomeXchange with identifier PXD004098. Molecular & Cellular

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“…The possibility is now open to further investigation of the molecular mechanisms within the sperm cell through which TBBPA exposure results in the detected effects. Different studies have demonstrated the presence of changes in the sperm proteome in infertile patients linked to protamine imbalances and DNA fragmentation (de Mateo et al, 2007;Martinez-Heredia et al, 2008;Oliva et al, 2008;Amaral et al, 2014). Therefore, important future extensions of our present work will be to explore in detail the overall sperm proteome and epigenome in TBBPA-exposed animals and their offspring, with the potential to provide additional important clues onto the mechanisms involved in the detected alterations.…”

Section: Discussionmentioning

confidence: 85%

The effect of tetrabromobisphenol A on protamine content and DNA integrity in mouse spermatozoa

et al. 2014

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SUMMARYTetrabromobisphenol A (TBBPA) is a widely used brominated flame retardant of increasing concern to human health because of its action as an endocrine disruptor. We have previously demonstrated that TBBPA is able to increase apoptosis of testicular cells and other changes in the first and second generations of mice exposed to TBBPA. However, the potential effects of TBBPA on mouse epididymal spermatozoa have not yet been investigated. Therefore, we initiated this study to determine whether TBBPA exposure could also result in increased DNA fragmentation in epididymal spermatozoa and whether it had an effect on the protamines as the major nuclear proteins. C57Bl/6J mouse pups (n = 10) were exposed to TBBPA (experimental group) during the gestation, lactation, pre-pubertal and pubertal periods up to the age of 70 days as previously described and compared to control mouse pups (n = 10) that were not exposed. The results demonstrate that TBBPA treatment results in a significantly decreased protamine 1/protamine 2 ratio (0.362 vs. 0.494; p < 0.001), increased total protamine/DNA ratio (0.517 vs. 0.324; p < 0.001) and increased number of terminal deoxynucleotidyl transferase dUTP nick end labelling positive spermatozoa (39.5% vs. 21.2%; p < 0.05) observed between TBBPA and control mice respectively. These findings indicate that TBBPA exposure, in addition to the resulting increased sperm DNA damage, also has the potential to alter the epigenetic marking of sperm chromatin through generation of an anomalous content and distribution of protamines. The possibility is now open to study whether the detected altered protamine content and DNA integrity are related to the previously observed second-generation effects upon TBBPA exposure.

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The combined human sperm proteome: cellular pathways and implications for basic and clinical science

Cited by 229 publications

References 245 publications

Identification of endogenous metabolites in human sperm cells using proton nuclear magnetic resonance (¹H-NMR) spectroscopy and gas chromatography-mass spectrometry (GC-MS)

Identification of endogenous metabolites in human sperm cells using proton nuclear magnetic resonance (¹H-NMR) spectroscopy and gas chromatography-mass spectrometry (GC-MS)

Human Spermatozoa Quantitative Proteomic Signature Classifies Normo- and Asthenozoospermia

The effect of tetrabromobisphenol A on protamine content and DNA integrity in mouse spermatozoa

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The combined human sperm proteome: cellular pathways and implications for basic and clinical science

Cited by 229 publications

References 245 publications

Identification of endogenous metabolites in human sperm cells using proton nuclear magnetic resonance (1H-NMR) spectroscopy and gas chromatography-mass spectrometry (GC-MS)

Identification of endogenous metabolites in human sperm cells using proton nuclear magnetic resonance (1H-NMR) spectroscopy and gas chromatography-mass spectrometry (GC-MS)

Human Spermatozoa Quantitative Proteomic Signature Classifies Normo- and Asthenozoospermia

The effect of tetrabromobisphenol A on protamine content and DNA integrity in mouse spermatozoa

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Identification of endogenous metabolites in human sperm cells using proton nuclear magnetic resonance (¹H-NMR) spectroscopy and gas chromatography-mass spectrometry (GC-MS)

Identification of endogenous metabolites in human sperm cells using proton nuclear magnetic resonance (¹H-NMR) spectroscopy and gas chromatography-mass spectrometry (GC-MS)