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Journal of Cellular and Molecular... Apr 2024Oligoasthenoteratospermia (OAT), characterized by abnormally low sperm count, poor sperm motility, and abnormally high number of deformed spermatozoa, is an important...
Oligoasthenoteratospermia (OAT), characterized by abnormally low sperm count, poor sperm motility, and abnormally high number of deformed spermatozoa, is an important cause of male infertility. Its genetic basis in many affected individuals remains unknown. Here, we found that CCDC157 variants are associated with OAT. In two cohorts, a 21-bp (g.30768132_30768152del21) and/or 24-bp (g.30772543_30772566del24) deletion of CCDC157 were identified in five sporadic OAT patients, and 2 cases within one pedigree. In a mouse model, loss of Ccdc157 led to male sterility with OAT-like phenotypes. Electron microscopy revealed misstructured acrosome and abnormal head-tail coupling apparatus in the sperm of Ccdc157-null mice. Comparative transcriptome analysis showed that the Ccdc157 mutation alters the expressions of genes involved in cell migration/motility and Golgi components. Abnormal Golgi apparatus and decreased expressions of genes involved in acrosome formation and lipid metabolism were detected in Ccdc157-deprived mouse germ cells. Interestingly, we attempted to treat infertile patients and Ccdc157 mutant mice with a Chinese medicine, Huangjin Zanyu, which improved the fertility in one patient and most mice that carried the heterozygous mutation in CCDC157. Healthy offspring were produced. Our study reveals CCDC157 is essential for sperm maturation and may serve as a marker for diagnosis of OAT.
Topics: Animals; Humans; Male; Mice; Asthenozoospermia; Infertility, Male; Mice, Knockout; Mutation; Oligospermia; Semen; Sperm Motility; Spermatozoa; Membrane Proteins
PubMed: 38509755
DOI: 10.1111/jcmm.18215 -
Reproductive Sciences (Thousand Oaks,... Jul 2024The methylation pattern of non-imprinting genes was little studied, although it is widely known that the abnormal methylation levels of imprinting genes are associated...
The methylation pattern of non-imprinting genes was little studied, although it is widely known that the abnormal methylation levels of imprinting genes are associated with different forms of male infertility. The purpose of this research was to assess the CREM gene's methylation status and seminal characteristics in infertile individuals who were potential intracytoplasmic sperm injection (ICSI) candidates. A total of 45 semen samples (15 normospermia, 15 asthenospermia, and 15 oligoasthenoteratospermia) were examined. Using aniline blue (AB) staining, we carried out conventional semen analysis, chromatin quality, and sperm maturity testing. DNA was taken from semen samples, and all isolated DNA was assessed using Nanodrop and gel electrophoresis. A quantitative methylation-specific polymerase chain reaction (Q-MSP) approach was used to quantify the methylation at the DMRs of the CREM gene. According to our findings, sperm count (P=0.012), concentration (P= 0.019), motility (P=0.006), progression (P=0.006), and normal morphology (P=0.004) were all inversely correlated with abnormal sperm chromatin condensation. Additionally, we noted that the methylation level of the CREM gene was considerably more significant in the oligoasthenoteratospermia group compared to the asthenospermia and normospermia groups (P<0.05). Additionally, sperm count (P=0.043), progression (P=0.026), and normal morphology (P=0.024) were all inversely linked with CREM methylation. Overall, the abnormal CREM methylation patterns have a negative impact on sperm parameters. Additionally, the CREM gene's DNA methylation status may serve as an epigenetic indicator of male infertility.
Topics: Humans; Male; DNA Methylation; Infertility, Male; Spermatozoa; Cyclic AMP Response Element Modulator; Adult; Sperm Motility; Semen Analysis; Sperm Count; Asthenozoospermia
PubMed: 38499948
DOI: 10.1007/s43032-024-01510-1 -
Reproductive Biomedicine Online May 2024Is the novel homozygous nonsense variant of AK7 associated with multiple morphological abnormalities of the sperm flagella (MMAF), a specific type of...
RESEARCH QUESTION
Is the novel homozygous nonsense variant of AK7 associated with multiple morphological abnormalities of the sperm flagella (MMAF), a specific type of oligoasthenoteratozoospermia leading to male infertility?
DESIGN
Whole-exome sequencing and Sanger sequencing were performed to identify potential gene variants. Immunoblotting and immunofluorescence were applied to confirm the relationship between mutated genes and disease phenotypes. The concentration of reactive oxygen species and the rate of apoptosis were measured to evaluate the mitochondrial function of spermatozoa. Transmission electron microscopy and scanning electron microscopy were employed to observe sperm ultrastructure.
RESULTS
A novel homozygous nonsense variant of AK7, c.1153A>T (p. Lys385*), was identified in two infertile siblings with asthenoteratozoospermia through whole-exome sequencing. Both immunoblotting and immunofluorescence assays showed practically complete absence of AK7 in the patient's spermatozoa. Additionally, the individual with the novel AK7 variant exhibited a phenotype characterized by severe oxidative stress and apoptosis caused by mitochondrial metabolic dysfunction of spermatozoa. Notably, remarkable flagellar defects with multiple axonemes in uniflagellate spermatozoa, accompanied by mitochondrial vacuolization, were observed; this has not been reported previously in patients with other AK7 variants.
CONCLUSIONS
This study found that a novel identified homozygous nonsense variant of AK7 may be associated with MMAF-related asthenoteratozoospermia. The observed functional associations between mitochondria and sperm flagellar assembly provide evidence for potential mutual regulation between AK7 and flagella-associated proteins during spermatogenesis.
Topics: Humans; Male; Sperm Tail; Codon, Nonsense; Homozygote; Infertility, Male; Asthenozoospermia; Adult; Spermatozoa; Exome Sequencing; Mitochondria; Pedigree
PubMed: 38492416
DOI: 10.1016/j.rbmo.2023.103765 -
Journal of Assisted Reproduction and... May 2024To identify the genetic causes of multiple morphological abnormalities in sperm flagella (MMAF) and male infertility in patients from two unrelated Han Chinese families.
PURPOSE
To identify the genetic causes of multiple morphological abnormalities in sperm flagella (MMAF) and male infertility in patients from two unrelated Han Chinese families.
METHODS
Whole-exome sequencing was conducted using blood samples from the two individuals with MMAF and male infertility. Hematoxylin and eosin staining and scanning electron microscopy were performed to evaluate sperm morphology. Ultrastructural and immunostaining analyses of the spermatozoa were performed. The HEK293T cells were used to confirm the pathogenicity of the variants.
RESULTS
We identified two novel homozygous missense ARMC2 variants: c.314C > T: p.P105L and c.2227A > G: p.N743D. Both variants are absent or rare in the human population genome data and are predicted to be deleterious. In vitro experiments indicated that both ARMC2 variants caused a slightly increased protein expression. ARMC2-mutant spermatozoa showed multiple morphological abnormalities (bent, short, coiled, absent, and irregular) in the flagella. In addition, the spermatozoa of the patients revealed a frequent absence of the central pair complex and disrupted axonemal ultrastructure.
CONCLUSION
We identified two novel ARMC2 variants that caused male infertility and MMAF in Han Chinese patients. These findings expand the mutational spectrum of ARMC2 and provide insights into the complex causes and pathogenesis of MMAF.
Topics: Humans; Male; Sperm Tail; Homozygote; Infertility, Male; Asthenozoospermia; Exome Sequencing; Adult; Spermatozoa; Mutation; Pedigree; HEK293 Cells; Asian People
PubMed: 38492154
DOI: 10.1007/s10815-024-03087-9 -
Experimental and Therapeutic Medicine Apr 2024Asthenozoospermia, a male fertility disorder, has a complex and multifactorial etiology. Moreover, the effectiveness of different treatments for asthenozoospermia...
Asthenozoospermia, a male fertility disorder, has a complex and multifactorial etiology. Moreover, the effectiveness of different treatments for asthenozoospermia remains uncertain. Hence, by using bioinformatics techniques, the present study aimed to determine the underlying genetic markers and pathogenetic mechanisms associated with asthenozoospermia due to abnormal spermatogenesis and inflammation of the reproductive tract. GSE160749 dataset was downloaded from the Gene Expression Omnibus database, and the data were filtered to obtain 1336 differentially expressed genes (DEGs) associated with asthenozoospermia. These DEGs were intersected with the epithelial mesenchymal transition datasets to yield 61 candidate DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed, and the results revealed that these candidate DEGs were significantly enriched in the enzyme-linked receptor pathway and the thyroid hormone pathway. A protein-protein interaction network was constructed to identify the key genes of asthenozoospermia. A total of five key genes were identified, among which was significantly upregulated, while , , and were significantly downregulated. These findings were validated by conducting reverse transcription-quantitative PCR for clinical semen samples. To determine the underlying molecular mechanisms, a regulatory network of transcription factors and miRNA-mRNA interactions was predicted. The expression levels of , and were positively associated with several related etiological genes of asthenozoospermia. In total, five key genes were closely associated with the level and type of immune cells; higher levels of activated B cells and CD8 T cells were observed in asthenozoospermia. Thus, the findings of the present study may provide clues to determine the underlying novel diagnostic genetic markers and treatment strategies for asthenozoospermia.
PubMed: 38476923
DOI: 10.3892/etm.2024.12434 -
Cureus Feb 2024Platelet-rich plasma (PRP) is a concentrated platelet preparation known for its regenerative properties due to the various growth factors it contains. Its application in...
Platelet-rich plasma (PRP) is a concentrated platelet preparation known for its regenerative properties due to the various growth factors it contains. Its application in the medical field, including dentistry, gynecology, and plastic surgery, has surged. In obstetrics and gynecology, PRP has shown promise in improving low libido, vaginal rejuvenation, ovarian reserve, and endometrial receptivity. This study presents a 29-year-old woman experiencing primary infertility attributed to low levels of anti-Müllerian hormone alongside the presence of asthenozoospermia in her husband's semen. After failed intrauterine insemination as well as in vitro fertilization (IVF), attempts at laparoscopic PRP treatment were administered before the second IVF cycle to enhance ovarian reserve and quality. The PRP treatment led to an increased follicle count, improved oocyte quality, and a successful pregnancy outcome in the second IVF cycle. PRP treatment promises to be effective in fertility treatments, potentially increasing ovarian reserve, improving oocyte quality, and enhancing successful pregnancy outcomes. This case report highlights its beneficial impact on a couple facing primary infertility, providing hope for patients with similar reproductive challenges.
PubMed: 38440028
DOI: 10.7759/cureus.53474 -
Cureus Jan 2024This report presents the cases of a 34-year-old male and a 29-year-old female who visited a fertility clinic and were experiencing primary infertility for the past three...
This report presents the cases of a 34-year-old male and a 29-year-old female who visited a fertility clinic and were experiencing primary infertility for the past three years. No previous medical history was identified in the couple. After a failed attempt of intrauterine insemination, the male partner was diagnosed with asthenozoospermia. A second attempt of intracytoplasmic sperm injection (ICSI) was performed which failed again. Subsequently, magnetic-activated cell sorting (MACS) technique was used as the sperm selection technique. The male patient's sperms were selected through MACS before ICSI. After performing MACS, successful pregnancy was achieved, which resulted in the production of blastocysts and a positive beta-human chorionic gonadotropin test. This case report highlights the prospect of successful results, despite the presence of sperm DNA fragmentation, and a comprehensive strategy for managing infertility issues. Promoting knowledge of lifestyle factors and how they affect fertility remains an essential aspect of comprehensive infertility care.
PubMed: 38420052
DOI: 10.7759/cureus.53148 -
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