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European Review For Medical and... Dec 2023Infertility impacts a substantial number of couples worldwide, and about 50% of cases are linked to male factors. The analysis of seminal fluid composition can improve...
OBJECTIVE
Infertility impacts a substantial number of couples worldwide, and about 50% of cases are linked to male factors. The analysis of seminal fluid composition can improve diagnostic accuracy and offer deeper insights into the pathophysiology of male factor infertility. This study seeks to identify novel markers for diagnosing and treating male infertility by comparing organic acid profiles in the seminal fluid of individuals with normospermia, oligospermia, and azoospermia.
PATIENTS AND METHODS
Semen samples were collected from men with normospermia, oligospermia, and azoospermia. The organic acid profile in the seminal fluid was analyzed using liquid chromatography-mass spectrometry/mass spectrometry (LC/MS-MS). Data analysis was performed using SPSS and MetaboAnalyst.
RESULTS
The study revealed significant differences in metabolite levels among normospermic, oligospermic, and azoospermic individuals. In groups with oligospermia, there were significant decreases in the levels of 2-OH-Isovaleric Acid, 3-Methyl-2-Oxovaleric Acid, Ethyl-Malonic Acid, Citric Acid, Oxoproline, Malic Acid, N-Acetyl-Aspartic Acid, Suberic Acid, Glutaconic Acid, and Succinic Acid. Similarly, individuals with azoospermia exhibited a notable reduction in the levels of Citric Acid, Malic Acid, and Suberic Acid. Furthermore, according to the Variable Importance in the Projection (VIP) score analysis, Ethyl-Malonic Acid, Glycolic Acid, and 3-Methyl-2-Oxovaleric Acid were identified as crucial factors for diagnosis and potential treatment strategies.
CONCLUSIONS
The data obtained from the study highlights the significant potential of metabolites in assessing infertility and gaining a more in-depth understanding of the underlying pathological mechanisms.
Topics: Humans; Male; Oligospermia; Azoospermia; Semen; Infertility, Male; Citric Acid
PubMed: 38164856
DOI: 10.26355/eurrev_202312_34791 -
Journal of Assisted Reproduction and... Jan 2023Modeling methods for busulfan-induced oligoasthenozoospermia are controversial. We aimed to systematically review the modeling method of busulfan-induced oligospermia... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Modeling methods for busulfan-induced oligoasthenozoospermia are controversial. We aimed to systematically review the modeling method of busulfan-induced oligospermia and asthenozoospermia, and analyze changes in various evaluation indicators at different busulfan doses over time.
METHODS
We searched the Cochrane Library, PubMed databases, Web of Science, the Chinese National Knowledge Infrastructure, and the Chinese Biomedical Literature Service System until April 9, 2022. Animal experiments of busulfan-induced spermatogenesis dysfunction were included and screened. The model mortality and parameters of the evaluation indicators were subjected to meta-analysis.
RESULTS
Twenty-nine animal studies were included (control/model: 669/1829). The mortality of mice increased with busulfan dose. Significant spermatogenesis impairment occurred within 5 weeks, regardless of busulfan dose (10-40 mg/kg). Testicular weight (weighted mean difference [WMD]: - 0.04, 95% CI: - 0.05, - 0.03), testicular index (WMD: - 2.10, 95% CI: - 2.43, - 1.76), and Johnsen score (WMD: - 4.67, 95% CI: - 5.99, - 3.35) were significantly decreased. The pooled sperm counts of the model group were reduced by 32.8 × 10/ml (WMD: - 32.8, 95% CI: - 44.34, - 21.28), and sperm motility decreased by 37% (WMD: - 0.37, 95% CI: - 0.47, - 0.27). Sperm counts decreased slightly (WMD: - 3.03, 95% CI: - 3.42, - 2.64) in an intratesticular injection of low-dose busulfan (4 - 6 mg/kg), and the model almost returned to normal after one seminiferous cycle.
CONCLUSION
The model using low-dose busulfan (10 - 20 mg/kg) returned to normal after 10 - 15 weeks. However, in some spermatogenesis cycles, testicular weight reduction and testicular spermatogenic function damage were not proportional to busulfan dose. Sperm counts and motility results in different studies had significant heterogeneity. Standard protocols for sperm assessment in animal models were needed to reduce heterogeneity between studies.
Topics: Humans; Mice; Male; Animals; Oligospermia; Busulfan; Asthenozoospermia; Sperm Count; Sperm Motility; Semen
PubMed: 36508035
DOI: 10.1007/s10815-022-02674-y -
Asian Journal of Andrology 2014The blood-testis barrier (BTB) is found between adjacent Sertoli cells in the testis where it creates a unique microenvironment for the development and maturation of... (Review)
Review
The blood-testis barrier (BTB) is found between adjacent Sertoli cells in the testis where it creates a unique microenvironment for the development and maturation of meiotic and postmeiotic germ cells in seminiferous tubes. It is a compound proteinous structure, composed of several types of cell junctions including tight junctions (TJs), adhesion junctions and gap junctions (GJs). Some of the junctional proteins function as structural proteins of BTB and some have regulatory roles. The deletion or functional silencing of genes encoding these proteins may disrupt the BTB, which may cause immunological or other damages to meiotic and postmeiotic cells and ultimately lead to spermatogenic arrest and infertility. In this review, we will summarize the findings on the BTB structure and function from genetically-modified mouse models and discuss the future perspectives.
Topics: Animals; Azoospermia; Blood-Testis Barrier; Disease Models, Animal; Infertility; Male; Mice; Mice, Transgenic; Oligospermia; Sertoli Cells; Spermatogenesis
PubMed: 24713828
DOI: 10.4103/1008-682X.125401 -
EMBO Reports Feb 2023Following meiotic recombination, each pair of homologous chromosomes acquires at least one crossover, which ensures accurate chromosome segregation and allows reciprocal...
Following meiotic recombination, each pair of homologous chromosomes acquires at least one crossover, which ensures accurate chromosome segregation and allows reciprocal exchange of genetic information. Recombination failure often leads to meiotic arrest, impairing fertility, but the molecular basis of recombination remains elusive. Here, we report a homozygous M1AP splicing mutation (c.1074 + 2T > C) in patients with severe oligozoospermia owing to meiotic metaphase I arrest. The mutation abolishes M1AP foci on the chromosome axes, resulting in decreased recombination intermediates and crossovers in male mouse models. M1AP interacts with the mammalian ZZS (an acronym for yeast proteins Zip2-Zip4-Spo16) complex components, SHOC1, TEX11, and SPO16. M1AP localizes to chromosomal axes in a SPO16-dependent manner and colocalizes with TEX11. Ablation of M1AP does not alter SHOC1 localization but reduces the recruitment of TEX11 to recombination intermediates. M1AP shows cytoplasmic localization in fetal oocytes and is dispensable for fertility and crossover formation in female mice. Our study provides the first evidence that M1AP acts as a copartner of the ZZS complex to promote crossover formation and meiotic progression in males.
Topics: Animals; Female; Male; Mice; Meiosis; Microtubule-Associated Proteins; DNA-Binding Proteins; Cell Cycle Proteins; Multiprotein Complexes
PubMed: 36440627
DOI: 10.15252/embr.202255778 -
Translational Andrology and Urology Mar 2021Infertility affects approximately 15% of couples. With infertility such a common problem in a generally healthy age group, complete evaluation is needed of both men and... (Review)
Review
Infertility affects approximately 15% of couples. With infertility such a common problem in a generally healthy age group, complete evaluation is needed of both men and women. Infertility work up for men includes a semen analysis, the results of which suggest various supplemental studies, including karyotype. Karyotype is indicated when a patient has findings on history or physical exam concerning for chromosomal abnormalities, azoospermia, or severe oligospermia (count <5 million/mL). The most common chromosomal numerical abnormality found on karyotype is Klinefelter syndrome which is classified as redundant sex chromosomes, with the most common chromosomal arrangement being 47, XXY. If a patient is found to have a chromosomal abnormality such as Klinefelter's, there is still a chance of fertility using testicular sperm extraction and in-vitro fertilization.
PubMed: 33850772
DOI: 10.21037/tau.2020.03.34 -
Frontiers in Endocrinology 2021
Topics: Animals; Humans; Infertility, Male; Male; Oligospermia; Oxidative Stress; Papillomavirus Infections; Reproduction
PubMed: 34867832
DOI: 10.3389/fendo.2021.797228 -
Translational Andrology and Urology Jul 2018For a significant number of couples worldwide, infertility is a harsh reality. As specialists in male infertility, much of our armamentarium lacks definitive,... (Review)
Review
For a significant number of couples worldwide, infertility is a harsh reality. As specialists in male infertility, much of our armamentarium lacks definitive, evidence-based therapies. For years, we have relied on manipulation of the male hormonal axis to treat those men who help carry the burden of infertility in their partnerships. Indeed, male factor infertility is the sole component of infertility in at least 20% of couples. Further compounding this dilemma is that 25% to 50% of males with infertility have no identifiable etiology and thus present a true management conundrum. This manuscript is an attempt to clarify what therapies exist for the treatment of male factor infertility. We have reviewed the relevant infertility literature honing, our focus on hormonal anomalies and their subsequent impact on fertility. Many of the therapies discussed have been utilized in practice for generations. Thus, this article attempts to provide the evidence-based literature to support the continued use of the current treatment paradigm. Furthermore, we recognize that any review beckons a discussion of what challenges and therapies await on the horizon. For instance, there has been significant interest in restoring spermatogenesis after testosterone replacement therapy (TRT). We explore the adverse long-term spermatogenic outcomes associated with TRT, which with the widespread use of TRT, will inevitably present a great challenge for male infertility specialists. Moreover, we discuss the role of varicocelectomy in the treatment of hypogonadism and infertility, review the association between growth hormone (GH) and male fertility and address the challenges presented by the rising prevalence of obesity.
PubMed: 30159242
DOI: 10.21037/tau.2018.04.03 -
Genetics in Medicine : Official Journal... Dec 2020Male infertility remains poorly understood at the molecular level. We aimed in this study to investigate the yield of a "genomics first" approach to male infertility.
PURPOSE
Male infertility remains poorly understood at the molecular level. We aimed in this study to investigate the yield of a "genomics first" approach to male infertility.
METHODS
Patients with severe oligospermia and nonobstructive azoospermia were investigated using exome sequencing (ES) in parallel with the standard practice of chromosomal analysis.
RESULTS
In 285 patients, 10.5% (n = 30) had evidence of chromosomal aberrations while nearly a quarter (n = 69; 24.2%) had a potential monogenic form of male infertility. The latter ranged from variants in genes previously reported to cause male infertility with or without other phenotypes in humans (24 patients; 8.4%) to those in novel candidate genes reported in this study (37 patients; 12.9%). The 33 candidate genes have biological links to male germ cell development including compatible mouse knockouts, and a few (TERB1 [CCDC79], PIWIL2, MAGEE2, and ZSWIM7) were found to be independently mutated in unrelated patients in our cohort. We also found that male infertility can be the sole or major phenotypic expression of a number of genes that are known to cause multisystemic manifestations in humans (n = 9 patients; 3.1%).
CONCLUSION
The standard approach to male infertility overlooks the significant contribution of monogenic causes to this important clinical entity.
Topics: Animals; Argonaute Proteins; Carrier Proteins; Cell Cycle Proteins; Chromosome Deletion; Chromosomes, Human, Y; Genomics; Humans; Infertility, Male; Male; Mice; Oligospermia; Sex Chromosome Aberrations
PubMed: 32719396
DOI: 10.1038/s41436-020-0916-0 -
Frontiers in Microbiology 2023Semen quality is decreasing worldwide, leading to increased male infertility. This study analyzed the microbiota of the gut, semen, and urine in individuals with semen...
INTRODUCTION
Semen quality is decreasing worldwide, leading to increased male infertility. This study analyzed the microbiota of the gut, semen, and urine in individuals with semen abnormalities to identify potential probiotics and pathogenic bacteria that affect semen parameters and help develop new methods for the diagnosis and treatment of patients with semen abnormalities.
METHODS
We recruited 12 individuals with normal semen parameters (control group), 12 with asthenospermia but no semen hyperviscosity (Group_1), 6 with oligospermia (Group_2), 9 with severe oligospermia or azoospermia (Group_3), and 14 with semen hyperviscosity only (Group_4). The semen, gut, and urine microbiota were examined by analyzing the 16S ribosomal RNA gene sequence using next-generation sequencing.
RESULTS
The gut microbes were clustered into the highest number of operational taxonomic units, followed by urine and semen. Furthermore, the α-diversity of gut microbes was highest and significantly different from that of urine and semen microbiota. The microbiota of the gut, urine, and semen were all significantly different from each other in terms of β-diversity. The gut abundance of was significantly reduced in groups 1, 3, and 4. Furthermore, the gut abundance of and was significantly decreased in Group_1, while that of was significantly increased in Group_3. The abundance of was significantly increased in the semen of groups 1 and 4. Finally, abundance was significantly reduced in the urine of groups 2 and 4.
DISCUSSION
This study comprehensively describes the differences in intestinal and genitourinary tract microbiota between healthy individuals and those with abnormal semen parameters. Furthermore, our study identified , , , and as potential probiotics. Finally, the study identified in the gut and in semen as potential pathogenic bacteria. Our study lays the foundation of a new approach to the diagnosis and treatment of male infertility.
PubMed: 37293215
DOI: 10.3389/fmicb.2023.1182320 -
Journal of Zhejiang University....With the rapid development of assisted reproductive technology, various reproductive disorders have been effectively addressed. Acupuncture-like therapies, including... (Review)
Review
With the rapid development of assisted reproductive technology, various reproductive disorders have been effectively addressed. Acupuncture-like therapies, including electroacupuncture (EA) and transcutaneous electrical acupoint stimulation (TEAS), become more popular world-wide. Increasing evidence has demonstrated that EA and TEAS are effective in treating gynecological disorders, especially infertility. This present paper describes how to select acupoints for the treatment of infertility from the view of theories of traditional Chinese medicine and how to determine critical parameters of electric pulses of EA/TEAS based on results from animal and clinical studies. It summarizes the principles of clinical application of EA/TEAS in treating various kinds of reproductive disorders, such as polycystic ovary syndrome (PCOS), pain induced by oocyte retrieval, diminished ovarian reserve, embryo transfer, and oligospermia/ asthenospermia. The possible underlying mechanisms mediating the therapeutic effects of EA/TEAS in reproductive medicine are also examined.
Topics: Acupuncture Points; Analgesia; Animals; Asthenozoospermia; Clinical Trials as Topic; Electroacupuncture; Embryo Transfer; Female; Genital Diseases, Female; Humans; Infertility, Female; Infertility, Male; Kidney; Male; Medicine, Chinese Traditional; Oligospermia; Oocyte Retrieval; Oocytes; Ovarian Reserve; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Rate; Reproductive Medicine; Transcutaneous Electric Nerve Stimulation; Uterus
PubMed: 28271655
DOI: 10.1631/jzus.B1600437