Sperm Proteome Analysis and Identification of Fertility-Associated Biomarkers in Unexplained Male Infertility

Selvam, Manesh Kumar Panner; Agarwal, Ashok; Pushparaj, Peter Natesan; Baskaran, Saradha; Bendou, Hocine

doi:10.3390/genes10070522

Cited by 52 publications

(36 citation statements)

References 43 publications

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“…Earlier proteomic studies have reported the alteration of mitochondrial proteins in oxidative stress-mediated male infertility [45,58,59]. Underexpression of the mitochondrial proteins were especially prominent in unexplained male infertility cases [44]. In our proteomics study, we have observed a state of underexpressed mitochondrial proteins in spermatozoa of idiopathic male infertility cases and their expression increased significantly after oral intake of ‘FH PRO for Men’ for a period of six months (Table 2).…”

Section: Discussionsupporting

confidence: 61%

“…Any defect in the structure or composition of sperm proteins negatively affects its functions such as capacitation, hyperactivation, acrosome reaction and fertilization [18]. Several proteomic studies have demonstrated that the proteins involved in the vital function pathways or protein modification pathways of spermatozoa were dysregulated in male infertility conditions [20,29,44,45,46,47]. In the antioxidant (‘FH PRO for Men’) treated group, we noticed that the majority of the proteins, specifically chaperones and their associated factors that are involved in stabilization of protein function, were overexpressed (Table 3).…”

Section: Discussionmentioning

confidence: 99%

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Effect of Antioxidant Supplementation on the Sperm Proteome of Idiopathic Infertile Men

et al. 2019

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Antioxidant supplementation in idiopathic male infertility has a beneficial effect on semen parameters. However, the molecular mechanism behind this effect has not been reported. The objective of this study was to evaluate the sperm proteome of idiopathic infertile men pre- and post-antioxidant supplementation. Idiopathic infertile men were provided with oral antioxidant supplementation once daily for a period of 6 months. Of the 379 differentially expressed proteins (DEPs) between pre- and post-antioxidant treatment patients, the majority of the proteins (n = 274) were overexpressed following antioxidant treatment. Bioinformatic analysis revealed the activation of oxidative phosphorylation pathway and upregulation of key proteins involved in spermatogenesis, sperm maturation, binding of sperm, fertilization and normal reproductive function. In addition, the transcriptional factors associated with antioxidant defense system (PPARGC1A) and free radical scavenging (NFE2L2) were predicted to be functionally activated post-treatment. Key DEPs, namely, NDUFS1, CCT3, PRKARA1 and SPA17 validated by Western blot showed significant overexpression post-treatment. Our novel proteomic findings suggest that antioxidant supplementation in idiopathic infertile men improves sperm function at the molecular level by modulating proteins involved in CREM signaling, mitochondrial function and protein oxidation. Further, activation of TRiC complex helped in nuclear compaction, maintenance of telomere length, flagella function, and expression of zona pellucida receptors for sperm–oocyte interaction.

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Section: Discussionsupporting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Effect of Antioxidant Supplementation on the Sperm Proteome of Idiopathic Infertile Men

et al. 2019

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“…Aberrant expression of sperm proteins was reported to affect the molecular mechanisms associated with motility, capacitation, acrosomal reaction, and sperm-oocyte interaction in unexplained male infertility cases [83]. For example, the proteins involved in chromatin assembly were defective in unexplained male infertility patients [84][85][86]. However, these findings require clinical validation.…”

Section: Proteins-sperm Proteomementioning

confidence: 99%

Male Infertility is a Women’s Health Issue—Research and Clinical Evaluation of Male Infertility Is Needed

Turner

Rambhatla

Schon

et al. 2020

Cells

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Infertility is a devastating experience for both partners as they try to conceive. Historically, when a couple could not conceive, the woman has carried the stigma of infertility; however, men and women are just as likely to contribute to the couple's infertility. With the development of assisted reproductive technology (ART), the treatment burden for male and unexplained infertility has fallen mainly on women. Equalizing this burden requires reviving research on male infertility to both improve treatment options and enable natural conception. Despite many scientific efforts, infertility in men due to sperm dysfunction is mainly diagnosed by a semen analysis. The semen analysis is limited as it only examines general sperm properties such as concentration, motility, and morphology. A diagnosis of male infertility rarely includes an assessment of internal sperm components such as DNA, which is well documented to have an impact on infertility, or other components such as RNA and centrioles, which are beginning to be adopted. Assessment of these components is not typically included in current diagnostic testing because available treatments are limited. Recent research has expanded our understanding of sperm biology and suggests that these components may also contribute to the failure to achieve pregnancy. Understanding the sperm's internal components, and how they contribute to male infertility, would provide avenues for new therapies that are based on treating men directly for male infertility, which may enable less invasive treatments and even natural conception.

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“…Male-factor infertility is thereby assumed to contribute to about half of the cases, although the actual causes remain unexplained in 30-50% of the men seeking medical help [Poongothai et al, 2009;Nieschlag et al, 2010;Massart et al, 2012;Hamada et al, 2013;Krausz and Riera-Escamilla, 2018;Ferlin et al, 2019]. In fact, the main biomarker for male sub-and infertility, semen analysis, cannot reliably discriminate fertile from infertile individuals [Kovac et al, 2013;Bracke et al, 2018;Cariati et al, 2019;Panner Selvam et al, 2019], and genetic analysis continues to be ineffective to date [Aston, 2014;Coutton et al, 2015;Song et al, 2016;Mitchell et al, 2017;Cariati et al, 2019]. On the other hand, clarification of the genetic causes is a prerequisite for developing a tailored therapy of male fertility impairment [Sullivan, 2004;Bonache et al, 2012].…”

mentioning

confidence: 99%

Fertility Relevance Probability Analysis Shortlists Genetic Markers for Male Fertility Impairment

Greither¹,

Schumacher²,

Dejung³

et al. 2020

Cytogenet Genome Res

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Impairment of male fertility is one of the major public health issues worldwide. Nevertheless, genetic causes of male sub- and infertility can often only be suspected due to the lack of reliable and easy-to-use routine tests. Yet, the development of a marker panel is complicated by the large quantity of potentially predictive markers. Actually, hundreds or even thousands of genes could have fertility relevance. Thus, a systematic method enabling a selection of the most predictive markers out of the many candidates is required. As a criterion for marker selection, we derived a gene-specific score, which we refer to as fertility relevance probability (FRP). For this purpose, we first categorized 2,753 testis-expressed genes as either candidate markers or non-candidates, according to phenotypes in male knockout mice. In a parallel approach, 2,502 genes were classified as candidate markers or non-candidates based on phenotypes in men. Subsequently, we conducted logistic regression analyses with evolutionary rates of genes (dN/dS), transcription levels in testis relative to other organs, and connectivity of the encoded proteins in a protein-protein interaction network as covariates. In confirmation of the procedure, FRP values showed the expected pattern, thus being overall higher in genes with known relevance for fertility than in their counterparts without corresponding evidence. In addition, higher FRP values corresponded with an increased dysregulation of protein abundance in spermatozoa of 37 men with normal and 38 men with impaired fertility. Present analyses resulted in a ranking of genes according to their probable predictive power as candidate markers for male fertility impairment. Thus, AKAP4, TNP1, DAZL, BRDT, DMRT1, SPO11, ZPBP, HORMAD1, and SMC1B are prime candidates toward a marker panel for male fertility impairment. Additional candidate markers are DDX4, SHCBP1L, CCDC155, ODF1, DMRTB1, ASZ1, BOLL, FKBP6, SLC25A31, PRSS21, and RNF17. FRP inference additionally provides clues for potential new markers, thereunder TEX37 and POU4F2. The results of our logistic regression analyses are freely available at the PreFer Genes website (https://prefer-genes.uni-mainz.de/).

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Sperm Proteome Analysis and Identification of Fertility-Associated Biomarkers in Unexplained Male Infertility

Cited by 52 publications

References 43 publications

Effect of Antioxidant Supplementation on the Sperm Proteome of Idiopathic Infertile Men

Effect of Antioxidant Supplementation on the Sperm Proteome of Idiopathic Infertile Men

Male Infertility is a Women’s Health Issue—Research and Clinical Evaluation of Male Infertility Is Needed

Fertility Relevance Probability Analysis Shortlists Genetic Markers for Male Fertility Impairment

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