Non-Invasive Diagnostics of Male Spermatogenesis from Seminal Plasma: Seminal Proteins

Ješeta, Michal; Pospíšilová, Anna; Mekiňová, Lenka; Franzová, Kateřina; Ventruba, Pavel; Lousová, Eva; Kempisty, Bartosz; Oždian, Tomáš; Žáková, Jana; Crha, Igor

doi:10.3390/diagnostics13152468

Cited by 8 publications

(4 citation statements)

References 74 publications

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“…Prostaglandin-H2 D-isomerase (PTGDS) is expressed in all male tissues, yet it was significantly decreased only in OA seminal plasma compared to fertile controls. This finding is supported by previous studies suggesting that PTGDS is promising biomarker of obstructive azoospermia ( 33 – 36 ). Maltase-glucoamylase (MGAM) was also reduced in OA seminal plasma compared to fertile controls, and was previously reported to be of significantly lower abundance in the seminal plasma of men after vasectomy ( 28 ), suggesting that it could be useful for assessing the presence of sperm.…”

Section: Discussionsupporting

confidence: 90%

Proteomic biomarkers in seminal plasma as predictors of reproductive potential in azoospermic men

Fietz,

Sgaier,

O’Donnell

et al. 2024

Front. Endocrinol.

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IntroductionAzoospermia, characterized by an absence of sperm in the ejaculate, represents the most severe form of male infertility. While surgical sperm retrieval in obstructive azoospermia (OA) is successful in the majority of cases, patients with non-obstructive azoospermia (NOA) show retrieval rates of only about 50% and thus frequently have unnecessary surgery. Surgical intervention could be avoided if patients without preserved spermatogenesis are identified preoperatively. This prospective study aimed to discover biomarkers in seminal plasma that could be employed for a non-invasive differential diagnosis of OA/NOA in order to rationalize surgery recommendations and improve success rates.MethodsAll patients signed written informed consent, underwent comprehensive andrological evaluation, received human genetics to exclude relevant pathologies, and patients with azoospermia underwent surgical sperm retrieval. Using label-free LC-MS/MS, we compared the proteomes of seminal plasma samples from fertile men (healthy controls (HC), n=8) and infertile men diagnosed with 1) OA (n=7), 2) NOA with successful sperm retrieval (mixed testicular atrophy (MTA), n=8), and 3) NOA without sperm retrieval (Sertoli cell-only phenotype (SCO), n=7). Relative abundance changes of two candidate markers of sperm retrieval, HSPA2 and LDHC, were confirmed by Western Blot.ResultsWe found the protein expression levels of 42 proteins to be significantly down-regulated (p ≤ 0.05) in seminal plasma from SCO NOA patients relative to HC whereas only one protein was down-regulated in seminal plasma from MTA patients. Analysis of tissue and cell expression suggested that the testis-specific proteins LDHC, PGK2, DPEP3, and germ-cell enriched heat-shock proteins HSPA2 and HSPA4L are promising biomarkers of spermatogenic function. Western blotting revealed a significantly lower abundance of LDHC and HSPA2 in the seminal plasma of men with NOA (SCO and MTA) compared to controls.DiscussionThe results indicate that certain testis-specific proteins when measured in seminal plasma, could serve as indicators of the presence of sperm in the testis and predict the success of sperm retrieval. Used in conjunction with conventional clinical assessments, these proteomic biomarkers may assist in the non-invasive diagnosis of idiopathic male infertility.

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Section: Discussionsupporting

confidence: 90%

Proteomic biomarkers in seminal plasma as predictors of reproductive potential in azoospermic men

Fietz,

Sgaier,

O’Donnell

et al. 2024

Front. Endocrinol.

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“…Seminal plasma contains proteins in a concentration of 35–55 mg/mL, with a mix of testicular, epididymal, seminal vesicle, and prostate proteins. About 60% of these proteins contribute to its enzymatic activity, including hydrolases and peptidases ( 67 , 68 ).…”

Section: Potential Non-invasive Biomarkers In Noamentioning

confidence: 99%

Non-invasive biomarkers for sperm retrieval in non-obstructive patients: a comprehensive review

Fontana,

Sirchia,

Pesenti

et al. 2024

Front. Endocrinol.

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Recent advancements in reproductive medicine have guided novel strategies for addressing male infertility, particularly in cases of non-obstructive azoospermia (NOA). Two prominent invasive interventions, namely testicular sperm extraction (TESE) and microdissection TESE (micro-TESE), have emerged as key techniques to retrieve gametes for assisted reproduction technologies (ART). Both heterogeneity and complexity of NOA pose a multifaceted challenge to clinicians, as the invasiveness of these procedures and their unpredictable success underscore the need for more precise guidance. Seminal plasma can be aptly regarded as a liquid biopsy of the male reproductive tract, encompassing secretions from the testes, epididymides, seminal vesicles, bulbourethral glands, and prostate. This fluid harbors a variety of cell-free nucleic acids, microvesicles, proteins, and metabolites intricately linked to gonadal activity. However, despite numerous investigations exploring potential biomarkers from seminal fluid, their widespread inclusion into the clinical practice remains limited. This could be partially due to the complex interplay of diverse clinical and genetic factors inherent to NOA that likely contributes to the absence of definitive biomarkers for residual spermatogenesis. It is conceivable that the integration of clinical data with biomarkers could increase the potential in predicting surgical procedure outcomes and their choice in NOA cases. This comprehensive review addresses the challenge of sperm retrieval in NOA through non-invasive biomarkers. Moreover, we delve into promising perspectives, elucidating innovative approaches grounded in multi-omics methodologies, including genomics, transcriptomics and proteomics. These cutting-edge techniques, combined with the clinical and genetics features of patients, could improve the use of biomarkers in personalized medical approaches, patient counseling, and the decision-making continuum. Finally, Artificial intelligence (AI) holds significant potential in the realm of combining biomarkers and clinical data, also in the context of identifying non-invasive biomarkers for sperm retrieval.

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“…Αs sperm cells mature, a protein known as ΤEX101 is broken down, producing fertile spermatozoa [23]. Αdditionally, the epididymis secretes the protein ECΜ1, a reliable marker for distinguishing between obstructive and non-obstructive azoospermia, with data indicating 81% sensitivity and 100% specificity [24]. By incorporating these biomarkers into diagnostic processes, clinicians can offer more precise treatment strategies for infertile men.…”

Section: μAle Infertility and Seminal Plasma Indicatorsmentioning

confidence: 99%

“…Male fertility problems include anomalies in the testicles, vasectomy, and non-obstructive or obstructive azoospermia can be predicted with the help of semen protein indicators [ 24 ]. Serum plasma levels of α-glucosidase, CRISP1/PAP, and TEX101 enable clinicians to differentiate between these clinical conditions [ 85 ].…”

Section: Transcriptomics Proteomics Metabolomicsmentioning

confidence: 99%

Integrative Assessment of Seminal Plasma Biomarkers: A Narrative Review Bridging the Gap between Infertility Research and Clinical Practice

Moustakli,

Zikopoulos,

Skentou

et al. 2024

JCM

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Infertility represents a significant global health challenge impacting millions of couples worldwide. Approximately half of all infertile couples exhibit compromised semen quality, indicative of diminished male fertility. While the diagnosis of male infertility traditionally relies on semen analysis, its limitations in providing a comprehensive assessment of male reproductive health have spurred efforts to identify novel biomarkers. Seminal plasma, a complex fluid containing proteins, lipids, and metabolites, has emerged as a rich source of such indicators. Reproduction depends heavily on seminal plasma, the primary transporter of chemicals from male reproductive glands. It provides a non-invasive sample for urogenital diagnostics and has demonstrated potential in the identification of biomarkers linked to illnesses of the male reproductive system. Τhe abundance of seminal proteins has enabled a deeper understanding of their biological functions, origins, and differential expression in various conditions associated with male infertility, including azoospermia, asthenozoospermia, oligozoospermia, teratozoospermia, among others. The true prevalence of male infertility is understated due to the limitations of the current diagnostic techniques. Τhis review critically evaluates the current landscape of seminal plasma biomarkers and their utility in assessing male infertility. Βy bridging the gap between research and clinical practice, the integrative assessment of seminal plasma biomarkers offers a multimodal approach to comprehensively evaluate male infertility.

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Non-Invasive Diagnostics of Male Spermatogenesis from Seminal Plasma: Seminal Proteins

Cited by 8 publications

References 74 publications

Proteomic biomarkers in seminal plasma as predictors of reproductive potential in azoospermic men

Proteomic biomarkers in seminal plasma as predictors of reproductive potential in azoospermic men

Non-invasive biomarkers for sperm retrieval in non-obstructive patients: a comprehensive review

Integrative Assessment of Seminal Plasma Biomarkers: A Narrative Review Bridging the Gap between Infertility Research and Clinical Practice

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