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Frontiers in Cell and Developmental... 2024Over 8% of couples worldwide are affected by infertility and nearly half of these cases are due to male-specific issues where the underlying cause is often unknown....
Over 8% of couples worldwide are affected by infertility and nearly half of these cases are due to male-specific issues where the underlying cause is often unknown. Therefore, discovery of new genetic factors contributing to male-specific infertility in model organisms can enhance our understanding of the etiology of this disorder. Here we show that murine ATP10A, a phospholipid flippase, is highly expressed in male reproductive organs, specifically the testes and vas deferens. Therefore, we tested the influence of ATP10A on reproduction by examining fertility of knockout mice. Our findings reveal that deficiency leads to male-specific infertility, but does not perturb fertility in the females. The deficient male mice exhibit smaller testes, reduced sperm count (oligozoospermia) and lower sperm motility (asthenozoospermia). Additionally, deficient mice display testes and vas deferens histopathological abnormalities, as well as altered total and relative amounts of hormones associated with the hypothalamic-pituitary-gonadal axis. Surprisingly, circulating testosterone is elevated 2-fold in the knockout mice while luteinizing hormone, follicle stimulating hormone, and inhibin B levels were not significantly different from WT littermates. The knockout mice also exhibit elevated levels of gonadotropin receptors and alterations to ERK, p38 MAPK, Akt, and cPLA-dependent signaling in the testes. was knocked out in the C57BL/6J background, which also carries an inactivating nonsense mutation in the closely related lipid flippase, We have corrected the nonsense mutation using CRISPR/Cas9 and determined that loss of alone is sufficient to cause infertility in male mice. Collectively, these findings highlight the critical role of ATP10A in male fertility in mice and provide valuable insights into the underlying molecular mechanisms.
PubMed: 38415274
DOI: 10.3389/fcell.2024.1310593 -
Life (Basel, Switzerland) Jan 2024The impact of sexual abstinence on sperm quality, particularly in pathological cases, is a subject of debate. We investigated the link between abstinence duration and...
BACKGROUND
The impact of sexual abstinence on sperm quality, particularly in pathological cases, is a subject of debate. We investigated the link between abstinence duration and semen quality in both normal and pathological samples.
METHODS
We analyzed semen samples from 4423 men undergoing fertility evaluation, comprising 1256 samples from healthy individuals and 3167 from those with conditions such as oligozoospermia, asthenozoospermia, teratozoospermia, or a combination of these factors, namely oligoasthenoteratozoospermia (OAT). Parameters including sperm concentration, the percentage of progressively motile spermatozoa, total motile sperm count, and the percentage of spermatozoa with normal morphology were assessed at various abstinence durations (each day, 0-2, 3-7, and >7 days).
RESULTS
Extended abstinence correlated with higher sperm concentration overall ( < 0.001), except in oligozoospermia. Longer abstinence reduced progressive motility in normal ( < 0.001) and teratozoospermic samples ( < 0.001). Shorter abstinence was linked to higher morphologically normal sperm in normal samples ( = 0.03), while longer abstinence did so in oligoasthenoteratozoospermic samples ( = 0.013).
CONCLUSION
The findings suggest that a prolonged abstinence time is linked to higher sperm concentration, while optimal sperm motility is observed after shorter abstinence periods. However, results regarding morphology remain inconclusive. Recommendations on abstinence duration should be tailored based on the specific parameter requiring the most significant improvement.
PubMed: 38398698
DOI: 10.3390/life14020188 -
Archivio Italiano Di Urologia,... Feb 2024To evaluate the influence of testicular cancer histology and stage on sperm parameters in cryopreserved samples collected prior to orchiectomy.
PURPOSE
To evaluate the influence of testicular cancer histology and stage on sperm parameters in cryopreserved samples collected prior to orchiectomy.
MATERIALS AND METHODS
We conducted a retrospective analysis of tumor histology, stage and sperm parameters of patients who underwent pre-orchiectomy sperm cryopreservation for testicular cancer between March 2010 and March 2023. The World Health Organization (WHO) 2010 sperm reference values were used to identify patients with subnormal semen parameters and to further categorize patients by sperm alteration. Localized disease was classified as Stage I, while metastatic disease encompassed Stages II and III. Continuous variables were compared using t-test or Mann Whitney U test, and categorical variables using Chi-square and Fishers exact test.
RESULTS
A total of 64 patients was identified, 48 (75%) classified as stage I and 16 (25%) classified as stage II/III. No difference was found in semen parameters between patients with seminoma and patients with non-seminoma germ cell tumor (NSGCT). Patients with stage II/III disease had significantly lower percentages of progressive motility (36% vs 53%, p=0.021) and total motility (60% vs 69%, p=0.015) than stage I patients. When categorizing by sperm alterations according to WHO 2010 reference values, patients with stage II/III disease had significantly higher proportions of asthenozoospermia (38% vs 15%, p=0.048) and teratozoospermia (63% vs 31%, p=0.027) than stage I patients. Elevated tumor markers were not associated with sperm abnormalities.
CONCLUSIONS
Patients with metastatic testicular cancer present with worse sperm quality than patients with localized disease. Sperm cryopreservation should be offered to all patients with testicular cancer, and especially emphasized in patients with metastatic disease.
Topics: Humans; Male; Semen; Testicular Neoplasms; Orchiectomy; Sperm Count; Retrospective Studies; Spermatozoa; Sperm Motility; Neoplasms, Germ Cell and Embryonal
PubMed: 38389451
DOI: 10.4081/aiua.2024.12238 -
International Journal of Molecular... Jan 2024Phosphorus-containing metabolites occupy a prominent position in cell pathways. The phosphorometabolomic approach in human sperm samples will deliver valuable...
Phosphorus-containing metabolites occupy a prominent position in cell pathways. The phosphorometabolomic approach in human sperm samples will deliver valuable information as new male fertility biomarkers could emerge. This study analyzed, by P-NMR, seminal plasma and whole semen from asthenozoospermic and normozoospermic samples (71% vs. 27% and 45% vs. 17%, total and progressive sperm motility, respectively), and also ejaculates from healthy donors. At least 16 phosphorus-containing metabolites involved in central energy metabolism and phospholipid, nucleotide, and nicotinamide metabolic pathways were assigned and different abundances between the samples with distinct sperm quality was detected. Specifically, higher levels of phosphocholine, glucose-1-phosphate, and to a lesser degree, acetyl phosphate were found in the asthenozoospermic seminal plasma. Notably, the phosphorometabolites implicated in lipid metabolism were highlighted in the seminal plasma, while those associated with carbohydrate metabolism were more abundant in the spermatozoa. Higher levels of phosphocholine, glucose-1-phosphate, and acetyl phosphate in the seminal plasma with poor quality suggest their crucial role in supporting sperm motility through energy metabolic pathways. In the seminal plasma, phosphorometabolites related to lipid metabolism were prominent; however, spermatozoa metabolism is more dependent on carbohydrate-related energy pathways. Understanding the presence and function of sperm phosphorylated metabolites will enhance our knowledge of the metabolic profile of healthy human sperm, improving assessment and differential diagnosis.
Topics: Humans; Male; Semen; Phosphorylcholine; Sperm Motility; Spermatozoa; Asthenozoospermia; Phosphorus; Semen Analysis; Organophosphates
PubMed: 38338962
DOI: 10.3390/ijms25031682 -
Journal of Cellular and Molecular... Feb 2024Several studies have highlighted the functional indispensability of methyltransferase-like 3 (METTL3) in the reproductive system. However, a review that comprehensively... (Review)
Review
Several studies have highlighted the functional indispensability of methyltransferase-like 3 (METTL3) in the reproductive system. However, a review that comprehensively interprets these studies and elucidates their relationships is lacking. Therefore, the present work aimed to review studies that have investigated the functions of METTL3 in the reproductive system (including spermatogenesis, follicle development, gametogenesis, reproductive cancer, asthenozoospermia and assisted reproduction failure). This review suggests that METTL3 functions not only essential for normal development, but also detrimental in the occurrence of disorders. In addition, promising applications of METTL3 as a diagnostic or prognostic biomarker and therapeutic target for reproductive disorders have been proposed. Collectively, this review provides comprehensive interpretations, novel insights, potential applications and future perspectives on the role of METTL3 in regulating the reproductive system, which may be a valuable reference for researchers and clinicians.
Topics: Male; Humans; Methyltransferases; RNA; Spermatogenesis; Reproduction; Genitalia
PubMed: 38332508
DOI: 10.1111/jcmm.18128 -
Aging Jan 2024Oligoasthenoteratozoospermia (OAT) decreases male fertility, seriously affecting the production of offspring. This study clarified the preventive impact of different...
Oligoasthenoteratozoospermia (OAT) decreases male fertility, seriously affecting the production of offspring. This study clarified the preventive impact of different moxibustion frequencies on OAT and selected the optimal frequency to elucidate the underlying mechanism. An OAT rat model was constructed by gavage of tripterygium glycosides (TGS) suspension. Daily moxibustion (DM) or alternate-day moxibustion (ADM) was administered on the day of TGS suspension administration. Finally, we selected DM for further study based on sperm quality and DNA fragmentation index, testicular and epididymal morphology, and reproductive hormone level results. Subsequently, the oxidative stress (OS) status was evaluated by observing the OS indices levels; malondialdehyde (MDA), 8-hydroxy-deoxyguanosine (8-OHdG), total antioxidant capacity (T-AOC), and total superoxide dismutase (T-SOD) in testicular tissue using colorimetry and enzyme-linked immunosorbent assay. Furthermore, heme oxygenase 1 (HO-1) and nuclear factor erythropoietin-2-related factor 2 (Nrf2) were evaluated using Western blotting. Immunohistochemistry was employed to locate and assess the expression of HO-1 and Nrf2 protein, while quantitative real-time polymerase chain reaction was utilized to detect their mRNA expression. MDA and 8-OHdG levels decreased following DM treatment, while T-SOD and T-AOC increased, suggesting that DM may prevent TGS-induced OAT in rats by decreasing OS in the testis. Furthermore, protein and mRNA expression of Nrf2 and HO-1 in the testis were elevated, indicating that DM may reduce OS by activating the signaling pathway of Nrf2/HO-1. Therefore, DM could prevent OAT in rats via the Nrf2/HO-1 pathway, thereby presenting a promising therapeutic approach against OAT.
Topics: Rats; Male; Animals; Humans; Heme Oxygenase-1; Rats, Sprague-Dawley; NF-E2-Related Factor 2; Tripterygium; Oligospermia; Glycosides; Moxibustion; Asthenozoospermia; Infertility, Male; Seeds; Oxidative Stress; Antioxidants; Signal Transduction; Superoxide Dismutase; RNA, Messenger
PubMed: 38277193
DOI: 10.18632/aging.205475 -
Biomedicines Jan 2024VPS13A, also known as chorein, whose loss of function causes chorea-acanthocytosis (ChAc), is characterized by Huntington's-disease-like neurodegeneration and...
VPS13A, also known as chorein, whose loss of function causes chorea-acanthocytosis (ChAc), is characterized by Huntington's-disease-like neurodegeneration and neuropsychiatric symptoms in addition to acanthocytosis in red blood cells. We previously reported that ChAc-model mice with a loss of chorein function exhibited male infertility, with asthenozoospermia and mitochondrial dysmorphology in the spermatozoa. Here, we report a novel aspect of chorein dysfunction in male fertility, particularly its role in spermatogenesis and mitochondrial integrity. An increase in anti-malondialdehyde antibody immunoreaction within the testes, predominantly observed at the advanced stages of sperm formation in chorein-deficient mice, suggests oxidative stress as a contributing factor to mitochondrial dysfunction and impaired sperm maturation. The chorein immunoreactivity in spermatids of wild-type mice accentuates its significance in sperm development. ChAc-model mice exhibit mitochondrial ultrastructural abnormalities, specifically during the late stages of sperm maturation, suggesting a critical timeframe for chorein's action in spermiogenesis. We observed an increase in TOM20 protein levels, indicative of disrupted mitochondrial import mechanisms. The concurrent decrease in metabolic enzymes such as IDH3A, LDHC, PGK2, and ACAT1 suggests a complex chorein-mediated metabolic network that is essential for sperm vitality. Additionally, heightened separation of cytoplasmic droplets from sperm highlights the potential membrane instability in chorein-deficient spermatozoa. Metabolomic profiling further suggests a compensatory metabolic shift, with elevated glycolytic and TCA-cycle substrates. Our findings suggest that chorein is involved in anti-ferroptosis and the maturation of mitochondrial morphology in the late stages of spermatogenesis, and its deficiency leads to asthenozoospermia characterized by membrane instability, abnormal cytosolic glycolysis, abnormal mitochondrial function, and a disrupted TCA cycle. Further analyses are required to unravel the molecular mechanisms that directly link these findings and to elucidate the role of chorein in spermatogenesis as well as its broader implications.
PubMed: 38275411
DOI: 10.3390/biomedicines12010240 -
BMC Microbiology Jan 2024Identification of intestinal flora composition is significant for exploring the cause and pathogenic mechanisms of the gut-testis axis and clarifying the relationship...
BACKGROUND
Identification of intestinal flora composition is significant for exploring the cause and pathogenic mechanisms of the gut-testis axis and clarifying the relationship between microbiota and infertility. Our study aimed to examine the alternation in gut microbiota composition and identify potential microbes associated with development of Asthenozoospermia (AS).
METHOD
A total of 580 males were recruited in the outpatient department of Tianjin Medical University General Hospital between September 2021 and March 2023. Sperm parameters were analyzed according to the WHO laboratory manual. The 16 S rRNA gene high-throughput sequencing was performed to detect the gut microbiota composition in fecal samples. LEfSe analysis was used to screen key microbiota. PICRUSt2 software was utilized to predict relevant pathways.
RESULTS
After rigorous screening, 60 isolated AS patients (AS group) and 48 healthy men (NC group) were enrolled. No significant differences were observed in demographic characteristics (p > 0.05), semen volume (p = 0.718), sperm concentration (p = 0.109), or total sperm count (p = 0.200). Sperm total motility and progressive motility were significantly decreased in the AS group (p < 0.001). AS patients had significantly lower alpha diversity indices (Chao1, observed OTUs, and PD Whole-tree; p < 0.05). The beta-diversity of gut microbiota in AS patients significantly differed from NC men (PCoA analysis, p = 0.001). Firmicutes, Bacteroidota, Proteobacteria, and Actinobacteria were the primary phyla, with the dominant genera including Bacteroides, Prevotella, and Blautia. Eleven key genera such as Escherichia_Shigella and Prevotellaceae_UCG_001 were identified by LEfSe analysis. Most of these genera were negatively correlated with sperm mobility. Eighty-eight KEGG pathways, including steroid biosynthesis and meiosis, were significantly enriched between the two groups.
CONCLUSIONS
It appears that gut microbiota composition in AS patients significantly differed from that in healthy men, and the development of AS might be associated with intestinal flora dysbiosis.
Topics: Humans; Male; Gastrointestinal Microbiome; Pilot Projects; Asthenozoospermia; Semen; Bacteroidetes; Dysbiosis; China; RNA, Ribosomal, 16S
PubMed: 38225541
DOI: 10.1186/s12866-023-03173-5 -
International Journal of Molecular... Dec 2023Reduced sperm motility and/or count are among the major causes of reduced fertility in men, and sperm membranes play an important role in the spermatogenesis and...
Reduced sperm motility and/or count are among the major causes of reduced fertility in men, and sperm membranes play an important role in the spermatogenesis and fertilization processes. However, the impact of sperm lipid composition on male fertility remains under-investigated. The aim of the present study was to perform a lipidomic analysis of human sperm membranes: we performed an untargeted analysis of membrane lipid composition in fertile (N = 33) and infertile subjects (N = 29). In parallel, we evaluated their serum lipid levels. Twenty-one lipids were identified by their mass/charge ratio and post-source decay spectra. Sulfogalactosylglycerolipid (SGG, seminolipid) was the most abundant lipid component in the membranes. In addition, we observed a significant proportion of PUFAs. Important differences have emerged between the fertile and infertile groups, leading to the identification of a lipid cluster that was associated with semen parameters. Among these, cholesterol sulfate, SGG, and PUFAs represented the most important predictors of semen quality. No association was found between the serum and sperm lipids. Dietary PUFAs and SGG have acknowledged antioxidant functions and could, therefore, represent sensitive markers of sperm quality and testicular function. Altogether, these results underline the important role of sperm membrane lipids, which act independently of serum lipids levels and may rather represent an independent marker of reproductive function.
Topics: Humans; Male; Semen Analysis; Semen; Lipidomics; Sperm Motility; Spermatozoa; Membrane Lipids; Cluster Analysis; Asthenozoospermia
PubMed: 38203468
DOI: 10.3390/ijms25010297 -
Archivio Italiano Di Urologia,... Nov 2023We aimed to assess seminal calbindin 2 (CALB 2) expression in men with different semen parameters as well as its correlation with reproductive hormones in azoospermic...
OBJECTIVES
We aimed to assess seminal calbindin 2 (CALB 2) expression in men with different semen parameters as well as its correlation with reproductive hormones in azoospermic patients and different semen parameters in oligoasthenoteratozoospermic patients. CALB 2 is also known as calretinin and 29 kDa calbindin.
MATERIALS AND METHODS
This prospective study was performed on 96 cases from the andrology outpatient clinic divided into 3 groups as follows: group 1 including 32 non obstructive azoospermic (NOA) patients, group 2 including 32 patients with oligoasthenoteratozoospermia (OAT), and Group 3 including normozoospermic individuals as controls. Semen analysis and estimation of seminal CALB 2 concentrations by enzyme linked immunosorbent assay (ELISA) technique were performed for all participants. Reproductive hormones were measured in nonobstructive NOA patients.
RESULTS
The mean seminal CALB 2 level was higher in OAT patients compared to NOA patients and controls (7.8 ± 1.30 ng/ml, 7.3 ± 0.80 and 7.4 ± 1.0, respectively). Furthermore, the study had shown strong positive correlations between CALB 2 and sperm normal forms in controls and OAT patients. In contrast, there was no significant correlation between seminal CALB 2 and any of the reproductive hormones measured in NOA patients.
CONCLUSIONS
Seminal CALB 2 may play a role in increasing the abnormal forms in OAT patients.
Topics: Humans; Male; Azoospermia; Oligospermia; Calbindin 2; Asthenozoospermia; Prospective Studies; Infertility, Male; Semen; Hormones
PubMed: 38193226
DOI: 10.4081/aiua.2023.11906