A systematic review identifying fertility biomarkers in semen: a clinical approach through Omics to diagnose male infertility

Llavanera, Marc; Delgado-Bermúdez, Ariadna; Ribas-Maynou, Jordi; Salas‐Huetos, Albert; Yeste, Marc

doi:10.1016/j.fertnstert.2022.04.028

Cited by 36 publications

(22 citation statements)

References 117 publications

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“…Accordingly, the application of routine semen analysis to diagnose male fertility has been controversial for many years ( 5 , 6 ). In recent years, omics, including genomic, proteomic and metabolomic techniques, have been used to analyze molecular-level information of samples to diagnose or treat male infertility ( 7 ). Indeed, in-depth analyses of sperm molecular composition and data mining have contributed to our understanding of sperm function.…”

Section: Introductionmentioning

confidence: 99%

A new perspective on semen quality of aged male: The characteristics of metabolomics and proteomics

Guo

Hao

et al. 2023

Front. Endocrinol.

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BackgroundSemen quality is negatively correlated with male age and is mainly quantified by a routine semen analysis, which is descriptive and inconclusive. Sperm proteins or semen metabolites are used as the intermediate or end-products, reflecting changes in semen quality, and hold much promise as a new biomarker to predict fertility in advanced-aged males.ObjectivesIn this study, we sought to assess whether the semen metabolome and proteome of aged males can affect semen quality and serve as biomarkers for predicting semen quality.Materials and methodsWe retrospectively analyzed 12825 males that underwent semen routine analysis to understand the age-dependent changes in sperm quality. To identify the difference between aged and young adults, metabolomics (n=60) analyses of semen and proteomics (n=12) analyses of sperm were conducted. Finally, integrated machine learning of metabolomics was conducted to screen biomarkers to identify aging semen.ResultsWe discovered that male age was positively correlated with sperm concentration as well as DNA fragmentation index(DFI), and negatively with progressive motile sperm count, total sperm count, sperm volume and progressive sperm motility. The differential metabolites were significantly enriched in various metabolic pathways, and four of these differential metabolites (Pipamperone, 2,2-Bis(hydroxymethyl)-2,2’,2’’-nitrilotriethanol, Arg-Pro and Triethyl phosphate) were utilized to establish a biomarker panel to identify aging semen. Proteomic analysis showed that differential proteins were significantly enriched in protein digestion and absorption and some energy-related pathways. An integrated analysis of the metabolome and proteome identified differential energy metabolism and oxidative stress-related proteins, which could explain the decreased motility and the increased DFI of aging spermDiscussion and conclusionWe provide compelling evidence that the changes in semen metabolome and sperm proteome are related to the decline of semen quality in aged males. Moreover, a biomarker panel based on four metabolites was established to identify aging semen.

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Section: Introductionmentioning

confidence: 99%

A new perspective on semen quality of aged male: The characteristics of metabolomics and proteomics

Guo

Hao

et al. 2023

Front. Endocrinol.

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“…Conventional semen analysis through a CASA system is the predominant method for the diagnosis and prognosis of male fertility disorders [11]. Yet, the use of molecular biomarkers has been proposed to be helpful to identify infertility etiologies and predict male fertility with simple and sensitive tools [15]. Although glutathione S-transferases, and speci cally GSMT3, have been shown to be related to sperm quality and male fertility in several mammalian species , little evidence is, to the best of the authors' knowledge, available regarding the physiological role of GSTM3 in human sperm and its potential utilization as a novel molecular biomarker.…”

Section: Discussionmentioning

confidence: 99%

“…For this reason, whether the conventional spermiogram can predict male fertility is under debate [13,14]. In the route towards improving sperm analysis, the use of molecular biomarkers has been suggested to predict sperm fertilizing potential [15]. For example, sperm DNA fragmentation (SDF) analysis has been proposed as a putative diagnostic parameter for fertility status [16].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Glutathione S-transferase Mu 3 (GSTM3) levels in sperm as a simple method to predict oxidative DNA damage and seminogram alterations

Llavanera

Ribas-Maynou

Mateo‐Otero

et al. 2022

Preprint

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Background. Previous evidence suggested sperm Glutathione S-transferase Mu 3 (GSTM3) to be essential for an appropriate mitochondrial function, plasma membrane stability and oxidative regulation of mammalian sperm. In humans, however, neither has this enzyme been related to semen alterations nor has it been reported to be associated to oxidative DNA damage and (in)fertility. Methods. The aim of the present study was to assess the utility of GSTM3 to predict spermiogram alterations and oxidative DNA damage in sperm. A total of 34 semen samples were collected, evaluated by conventional semen analysis, and subsequently cryopreserved. Frozen-thawed sperm samples were assessed for DNA fragmentation and the presence, localization and content of GSTM3. Results. Sperm GSTM3 content was positively associated to sperm quality parameters (P < 0.05). Specifically, lower levels of this antioxidant enzyme were observed in asthenoteratozoospermic and oligoasthenoteratozoospermic men (P < 0.05), but not idiopathic infertile patients (P > 0.05), when compared to normospermic samples. Moreover, sperm GSTM3 was negatively associated to oxidative DNA damage (P < 0.05). Finally, the ability to predict spermiogram alterations was determined by ROC curve analysis using GSTM3 alone (AUC of 0.89; P < 0.05), and in combination with oxidative DNA damage (AUC of 0.91; P < 0.05). Conclusions. Although the limited sample size of the present study warrants further studies and clinical trials with larger sample sets, our results set the ground for using GSTM3 as a novel biomarker and therapy target for male infertility and oxidative DNA damage in sperm.

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“…The above evidence shows that SDF and sperm miRNAs are important molecular aspects involved in the reproduction [ 11 ]. New and more specific biomarkers would be useful in clinical practice to improve the work up of the infertile couple for counseling purposes.…”

Section: Introductionmentioning

confidence: 99%

Sperm DNA Fragmentation and Sperm-Borne miRNAs: Molecular Biomarkers of Embryo Development?

Conflitti

Cicolani

Buonacquisto

et al. 2023

IJMS

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The evaluation of morpho-functional sperm characteristics alone is not enough to explain infertility or to predict the outcome of Assisted Reproductive Technologies (ART): more sensitive diagnostic tools are needed in clinical practice. The aim of the present study was to analyze Sperm DNA Fragmentation (SDF) and sperm-borne miR-34c-5p and miR-449b-5p levels in men of couples undergoing ART, in order to investigate any correlations with fertilization rate, embryo quality and development. Male partners (n = 106) were recruited. Semen analysis, SDF evaluation and molecular profiling analysis of miR-34c-5p and miR-449b-5p (in 38 subjects) were performed. Sperm DNA Fragmentation evaluation- a positive correlation between SDF post sperm selection and the percentage of low-quality embryos and a negative correlation with viable embryo were found. SDF > 2.9% increased the risk of obtaining a non-viable embryo by almost 4-fold. Sperm miRNAs profile—we found an association with both miRNAs and sperm concentration, while miR-449b-5p is positively associated with SDF. Moreover, the two miRNAs are positively correlated. Higher levels of miR-34c-5p compared to miR-449b-5p increases by 14-fold the probability of obtaining viable embryos. This study shows that SDF, sperm miR-34c-5p, and miR-449b-5p have a promising role as biomarkers of semen quality and ART outcome.

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A systematic review identifying fertility biomarkers in semen: a clinical approach through Omics to diagnose male infertility

Cited by 36 publications

References 117 publications

A new perspective on semen quality of aged male: The characteristics of metabolomics and proteomics

A new perspective on semen quality of aged male: The characteristics of metabolomics and proteomics

Evaluation of Glutathione S-transferase Mu 3 (GSTM3) levels in sperm as a simple method to predict oxidative DNA damage and seminogram alterations

Sperm DNA Fragmentation and Sperm-Borne miRNAs: Molecular Biomarkers of Embryo Development?

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