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The Tohoku Journal of Experimental... Jun 2024
PubMed: 38839357
DOI: 10.1620/tjem.2024.J040 -
Genetic Testing and Molecular Biomarkers Jun 2024Asthenozoospermia is the most common factor of male infertility, mainly caused by multiple morphological abnormalities of the sperm flagella (MMAF) and primary ciliary...
Asthenozoospermia is the most common factor of male infertility, mainly caused by multiple morphological abnormalities of the sperm flagella (MMAF) and primary ciliary dyskinesia (PCD). Previous studies have shown that genetic factors may contribute to MMAF and PCD. The study aimed to identify novel potentially pathogenic gene mutations in a Chinese infertile man with MMAF and PCD-like phenotypes. A Chinese infertile man with MMAF and PCD was enrolled in this study. Whole exome sequencing and Sanger sequencing were performed to identify potential causative genes and mutations. A novel homozygous missense mutation (c.1450G>A; p.E484K) of was finally identified and Sanger sequencing confirmed that the patient carried the homozygous mutation, which was inherited from his parents. We reported the first homozygous missense mutation in infertile men with MMAF but had other milder PCD symptoms. Our findings not only broaden the disease-causing mutation spectrum of but also provide new insight into the correlation between mutations and MMAF.
PubMed: 38837151
DOI: 10.1089/gtmb.2023.0263 -
Cellular and Molecular Biology... Jun 2024Asthenospermia is a predominant cause of male infertility, and antioxidant supplements can be effective in treating asthenospermia. We demonstrate the antioxidant...
Asthenospermia is a predominant cause of male infertility, and antioxidant supplements can be effective in treating asthenospermia. We demonstrate the antioxidant potential of traditional Chinese medicine, the Yishenhuoxue (YSHX) formula, in treating polyglycosides of Tripterygium wilfordii (GTW)-induced asthenospermia in rats. Fifty male rats were randomly divided into the normal, model, and treatment groups. HE staining was used to evaluate the improvement of spermatogenic function of rats, and TBA reaction, qRT-PCR, Western Blot and other methods were used to determine the changes of oxidative stress indicators and to evaluate the improvement of antioxidant capacity of rats by YSHX. Comparison with the model group showed significant improvement in pathological damage caused by GTW to seminiferous tubules. MDA and NO content in rat testes decreased, especially in middle- and high-dosage groups. No significant changes were observed in SOD and CAT activity or mRNA expression. GSH-Px activity and GSH mRNA expression were significantly higher in the low-dosage group than in the model group. Compared to the model group, GR activity was significantly lower in the middle and high dosage groups, while the mRNA expression was higher. The PKC-beta level increased, while p-ERK1/2, NF-κB, and the ratio of p-ERK1/2*(ERK1/2)-1 decreased significantly in the treatment groups. Therefore, YSHX can alleviate GTW-induced testicular damage, enhance GSH-Px activity, regulate GSH redox cycling, and mitigate oxidative stress injury. Furthermore, YSHX can promote PKC-beta expression and inhibit the phosphorylation of ERK1/2 and NF-κB. Using YSHX may be an effective way to increase sperm motility via the PKC-ERK1/2-NF-ĸB axis.
Topics: Animals; Male; Antioxidants; Drugs, Chinese Herbal; Asthenozoospermia; Rats, Sprague-Dawley; Oxidative Stress; Signal Transduction; Rats; NF-kappa B; Testis; Tripterygium; Malondialdehyde; Superoxide Dismutase
PubMed: 38836655
DOI: 10.14715/cmb/2024.70.6.34 -
Food & Function Jun 2024: Macronutrients are the main part of the human diet and can affect multiple health outcomes. Nevertheless, associations between dietary macronutrient quality and...
: Macronutrients are the main part of the human diet and can affect multiple health outcomes. Nevertheless, associations between dietary macronutrient quality and asthenozoospermia risk have not been reported to date. Thus, this study aimed to be the first to explore the associations between macronutrient quality and asthenozoospermia risk using the novel multidimensional macronutrient quality index (MQI). : A case-control study was conducted at infertility clinics of Shengjing Hospital of China Medical University during June and December 2020, including 552 asthenozoospermia cases and 585 normozoospermia controls. Data on diet were collected using a validated food frequency questionnaire. MQI was estimated according to the carbohydrate quality index (CQI), fat quality index (FQI), and protein quality index (PQI). Binary logistic regression models were performed to calculate the odds ratio (OR) with a 95% confidence interval (CI). Subgroup and interaction analyses were performed based on age, body mass index, physical activity, smoking, drinking, and education level. Dose-response relationships were evaluated by restricted cubic splines. Sensitivity analyses were performed in two ways. First, participants with a dietary change were excluded to lower potential reverse causation. Then, we used the healthy plate protein source quality index instead of PQI to redefine MQI. : No statistically significant association was observed between dietary MQI and asthenozoospermia risk (OR = 1.24, 95% CI: 0.88-1.73). The sub-indices of MQI, CQI, FQI, and PQI, failed to be identified as having a statistically significant association with asthenozoospermia risk (OR = 1.35, 95% CI: 0.92-1.97 for CQI; OR = 1.13, 95% CI: 0.84-1.53 for FQI; OR = 1.28, 95% CI: 0.92-1.78 for PQI). However, CQI showed a positive association with the risk of asthenozoospermia among non-drinkers ( < 0.05) and highly educated participants (OR = 1.82, 95% CI: 1.13-2.94; < 0.05). Additionally, there was a multiplicative interaction between CQI and education level for asthenozoospermia risk ( < 0.05). : Our findings demonstrated no association of MQI and its sub-indices with asthenozoospermia risk except for CQI. Although our findings are mostly non-significant, they contribute novel knowledge to this research field and lay the foundation for future studies.
Topics: Humans; Male; Asthenozoospermia; Case-Control Studies; Adult; China; Nutrients; Diet; Risk Factors; Body Mass Index
PubMed: 38819120
DOI: 10.1039/d4fo01234h -
Frontiers in Endocrinology 2024Although the effectiveness of pentoxifylline (PF) as a selective inhibitor of phosphodiesterase to enhance sperm motility through increasing cyclic nucleotide in cases...
INTRODUCTION
Although the effectiveness of pentoxifylline (PF) as a selective inhibitor of phosphodiesterase to enhance sperm motility through increasing cyclic nucleotide in cases of absolute asthenozoospermia has been demonstrated for ICSI, data related to babies born from the PF-ICSI are still severely lacking. Concerns have been raised regarding the potential embryotoxicity of PF due to the controversial results obtained from the analysis of this compound on animal embryo development. This study aimed to determine whether the application of PF to trigger frozen-thawed TESA (testicular sperm aspiration) spermatozoa increases the risk of adverse obstetric and neonatal outcomes compared with non-PF frozen-thawed TESA ICSI and conventional ICSI using fresh ejaculation.
MATERIALS AND METHODS
A total of 5438 patients were analyzed in this study, including 240 patients underwent PF-TESA ICSI (ICSI using PF triggered frozen-thawed testicular spermatozoa), 101 patients underwent non-PF TESA ICSI (ICSI using frozen-thawed testicular spermatozoa) and 5097 patients underwent conventional ICSI using fresh ejaculation. Propensity score matching was executed to control the various characteristics of patients.
RESULTS
No significant differences in pregnancy outcomes were observed among the three groups (PF-TESA ICSI, non-PF TESA ICSI and conventional ICSI), including biochemical pregnancy, clinical pregnancy, implantation, miscarriage, ectopic pregnancy, multiple pregnancy, and live birth, following propensity score matching. Additionally, neonatal outcomes were found to be similar among the three groups, with no statistical differences observed in the birth defect, birth weight, gestational age, preterm birth, and early-neonatal death.
DISCUSSION AND CONCLUSION
PF-ICSI may be an alternative treatment in patients using frozen-thawed testicular spermatozoa, resulting in comparable pregnancy and neonatal outcomes.
Topics: Humans; Pentoxifylline; Pregnancy; Female; Male; Sperm Injections, Intracytoplasmic; Adult; Pregnancy Outcome; Spermatozoa; Cryopreservation; Infant, Newborn; Pregnancy Rate; Sperm Retrieval; Retrospective Studies; Semen Preservation
PubMed: 38812814
DOI: 10.3389/fendo.2024.1364285 -
Journal of Biomedical Research May 2024Reliable molecular biomarkers to predict fertility remain scarce. The current study explored the potential of testis-specific RNAs as biomarkers for male infertility...
Reliable molecular biomarkers to predict fertility remain scarce. The current study explored the potential of testis-specific RNAs as biomarkers for male infertility and sperm quality. Using RT-PCR and RT-qPCR assays, we identified seven circular RNAs from the human gene in human sperm. We found that sperm RNA exhibited a significantly decreased expression in asthenozoospermia while and expression decreased in teratozoospermia, compared with the controls. Furthermore, expression exhibited a negative correlation with sperm DNA Fragmentation Index (DFI), and levels were correlated with both fertilization and cleavage rates involving assisted reproductive technologies. Further functional analyses in a transgenic fly model lent support for the roles of RNAs in sperm development and human fertility. Collectively, our findings support that sperm RNAs may serve as diagnostic biomarkers for assessing sperm motility and DNA quality. Hence clinical application and significance of sperm circular RNAs in assisted reproductive technologies warrant further investigation.
PubMed: 38808558
DOI: 10.7555/JBR.37.20230296 -
Scientific Reports May 2024Testicular adrenal rest tumor (TART) is a prevalent complication associated with congenital adrenal hyperplasia (CAH), culminating in gonadal dysfunction and...
Testicular adrenal rest tumor (TART) is a prevalent complication associated with congenital adrenal hyperplasia (CAH), culminating in gonadal dysfunction and infertility. Early hormonal intervention is preventive, but excessive glucocorticoid poses risks. Developing reliable methods for early TART diagnosis and monitoring is crucial. The present study aims to formulate a scoring system to identify high-risk infertility through analysis of TART ultrasound features. Grayscale and power Doppler ultrasound were employed in this retrospective study to evaluate testicular lesions in male CAH patients. Lesion assessment encompassed parameters such as range, echogenicity, and blood flow, and these were subsequently correlated with semen parameters. Results of 49 semen analyzes from 35 patients demonstrated a notable inverse correlation between lesion scores and both sperm concentration (r = - 0.83, P < 0.001) and progressive motility (r = - 0.56, P < 0.001). The ROC curve areas for evaluating oligospermia and asthenozoospermia were calculated as 0.94 and 0.72, respectively. Establishing a lesion score threshold of 6 revealed a sensitivity of 75.00% and specificity of 93.94% for oligospermia and a sensitivity of 53.85% and specificity of 100.00% for asthenozoospermia. These findings underscore the potential utility of incorporating ultrasound into routine CAH patient management, facilitating timely interventions to preserve male fertility.
Topics: Humans; Male; Adrenal Hyperplasia, Congenital; Adult; Retrospective Studies; Infertility, Male; Ultrasonography; Risk Assessment; Semen Analysis; Testis; Young Adult; Adrenal Rest Tumor
PubMed: 38802468
DOI: 10.1038/s41598-024-62954-8 -
Journal of Proteomics Jul 2024Protein lysine modifications (PLMs) are hotspots of post-translational modifications and are involved in many diseases; however, their role in human sperm remains...
Protein lysine modifications (PLMs) are hotspots of post-translational modifications and are involved in many diseases; however, their role in human sperm remains obscure. This study examined the presence and functional roles of a classical PLM (lysine acetylation, Kac) and three novel PLMs (lysine malonylation, Kmal; lysine succinylation, Ksucc; lysine crotonylation, Kcr) in human sperm. Immunoblotting and immunofluorescence assays revealed modified proteins (15-150 kDa) in the tails of human sperm. An immunoaffinity approach coupled with liquid chromatography/tandem mass spectrometry revealed 1423 Kac sites in 680 proteins, 196 Kmal sites in 118 proteins, 788 Ksucc sites in 251 proteins, and 1836 Kcr sites in 645 proteins. These modified proteins participate in a variety of biological processes and metabolic pathways. Crosstalk analysis demonstrated that proteins involved in the sperm energy pathways of glycolysis, oxidative phosphorylation, the citrate cycle, fatty acid oxidation, and ketone body metabolism were modified by at least one of these modifications. In addition, these modifications were found in 62 male fertility-related proteins that weave a protein-protein interaction network associated with asthenoteratozoospermia, asthenozoospermia, globozoospermia, spermatogenic failure, hypogonadotropic hypogonadism, and polycystic kidney disease. Our findings shed light on the functional role of PLMs in male reproduction. SIGNIFICANCE: Protein lysine modifications (PLMs) are hotspots of posttranslational modifications and are involved in many diseases. This study revealed the presence of a classical PLM (lysine acetylation) and three novel PLMs (lysine malonylation, lysine succinylation, and lysine crotonylation) in human sperm tails. The modified proteins participate in a variety of biological processes and metabolic pathways. In addition, these modifications were found in 62 male infertility-associated proteins and could serve as potential diagnostic markers and therapeutic targets for male infertility.
Topics: Humans; Male; Lysine; Protein Processing, Post-Translational; Spermatozoa; Acetylation; Proteomics; Proteome; Fertility; Infertility, Male
PubMed: 38797435
DOI: 10.1016/j.jprot.2024.105213 -
Genes May 2024Several genes are implicated in spermatogenesis and fertility regulation, and these genes are presently being analysed in clinical practice due to their involvement in... (Review)
Review
Several genes are implicated in spermatogenesis and fertility regulation, and these genes are presently being analysed in clinical practice due to their involvement in male factor infertility (MFI). However, there are still few genetic analyses that are currently recommended for use in clinical practice. In this manuscript, we reviewed the genetic causes of qualitative sperm defects. We distinguished between alterations causing reduced sperm motility (asthenozoospermia) and alterations causing changes in the typical morphology of sperm (teratozoospermia). In detail, the genetic causes of reduced sperm motility may be found in the alteration of genes associated with sperm mitochondrial DNA, mitochondrial proteins, ion transport and channels, and flagellar proteins. On the other hand, the genetic causes of changes in typical sperm morphology are related to conditions with a strong genetic basis, such as macrozoospermia, globozoospermia, and acephalic spermatozoa syndrome. We tried to distinguish alterations approved for routine clinical application from those still unsupported by adequate clinical studies. The most important aspect of the study was related to the correct identification of subjects to be tested and the correct application of genetic tests based on clear clinical data. The correct application of available genetic tests in a scenario where reduced sperm motility and changes in sperm morphology have been observed enables the delivery of a defined diagnosis and plays an important role in clinical decision-making. Finally, clarifying the genetic causes of MFI might, in future, contribute to reducing the proportion of so-called idiopathic MFI, which might indeed be defined as a subtype of MFI whose cause has not yet been revealed.
Topics: Humans; Male; Spermatozoa; Sperm Motility; Asthenozoospermia; Infertility, Male; Teratozoospermia; DNA, Mitochondrial; Genetic Testing
PubMed: 38790229
DOI: 10.3390/genes15050600 -
Journal of Human Genetics May 2024Human infertility affects 10-15% of couples. Asthenozoospermia accounts for 18% of men with infertility and is a common male infertility phenotype. The nexin-dynein...
Human infertility affects 10-15% of couples. Asthenozoospermia accounts for 18% of men with infertility and is a common male infertility phenotype. The nexin-dynein regulatory complex (N-DRC) is a large protein complex in the sperm flagellum that connects adjacent doublets of microtubules. Defects in the N-DRC can disrupt cilia/flagellum movement, resulting in primary ciliary dyskinesia and male infertility. Using whole-exome sequencing, we identified a pathological homozygous variant of the dynein regulatory complex subunit 3 (DRC3) gene, which expresses leucine-rich repeat-containing protein 48, a component of the N-DRC, in a patient with asthenozoospermia. The variant ENST00000313838.12: c.644dup (p. Glu216GlyfsTer36) causes premature translational arrest of DRC3, resulting in a dysfunctional DRC3 protein. The patient's semen count, color, and pH were normal according to the reference values of the World Health Organization guidelines; however, sperm motility and progressive motility were reduced. DRC3 protein was not detected in the patient's sperm and the ultrastructure of the patient's sperm flagella was destroyed. More importantly, the DRC3 variant reduced its interaction with other components of the N-DRC, including dynein regulatory complex subunits 1, 2, 4, 5, 7, and 8. Our data not only revealed the essential biological functions of DRC3 in sperm flagellum movement and structure but also provided a new basis for the clinical genetic diagnosis of male infertility.
PubMed: 38769386
DOI: 10.1038/s10038-024-01253-6