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The Journal of Biological Chemistry Jun 2023N6-methyladenosine (m6A) is the most prevalent reversible RNA modification in the mammalian transcriptome. It has recently been demonstrated that m6A is crucial for male...
N6-methyladenosine (m6A) is the most prevalent reversible RNA modification in the mammalian transcriptome. It has recently been demonstrated that m6A is crucial for male germline development. Fat mass and obesity-associated factor (FTO), a known m6A demethylase, is widely expressed in human and mouse tissues and is involved in manifold biological processes and human diseases. However, the function of FTO in spermatogenesis and male fertility remains poorly understood. Here, we generated an Fto knockout mouse model using CRISPR/Cas9-mediated genome editing techniques to address this knowledge gap. Remarkably, we found that loss of Fto in mice caused spermatogenesis defects in an age-dependent manner, resulting from the attenuated proliferation ability of undifferentiated spermatogonia and increased male germ cell apoptosis. Further research showed that FTO plays a vital role in the modulation of spermatogenesis and Leydig cell maturation by regulating the translation of the androgen receptor in an m6A-dependent manner. In addition, we identified two functional mutations of FTO in male infertility patients, resulting in truncated FTO protein and increased m6A modification in vitro. Our results highlight the crucial effects of FTO on spermatogonia and Leydig cells for the long-term maintenance of spermatogenesis and expand our understanding of the function of m6A in male fertility.
Topics: Animals; Humans; Male; Mice; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Cell Differentiation; Mutation; Spermatogenesis; Age Factors; Female; Fertility; Gene Deletion; Oligospermia
PubMed: 37146971
DOI: 10.1016/j.jbc.2023.104783 -
Oxidative Medicine and Cellular... 2018The aim of the study was to evaluate the parameters of oxidative stress and antioxidant defense in relation to the levels of proinflammatory cytokines and chemokines in...
The aim of the study was to evaluate the parameters of oxidative stress and antioxidant defense in relation to the levels of proinflammatory cytokines and chemokines in patients diagnosed with oligozoospermia and asthenozoospermia. Based on the basic parameters of the spermogram, the examined group ( = 243) was divided into three groups: oligospermic group (sperm count less than 15 × 10/ml) consisting of 152 men, astenozoospermic group (less than 40% of progressively moving sperm cells) consisting of 142 men, and oligoastenozoospermic group (both criteria met) consisting of 90 men. The control group consisted of 103 males with normal semen profile according to the WHO criteria. Total superoxide dismutase (SOD) activity in seminal plasma and spermatozoa lysate was significantly lower by 12% and 22%, respectively, in males with oligospermia than in the control group. Analogically, Mn-SOD activity in spermatozoa lysate was significantly lower in males with oligospermia, asthenospermia, and oligoasthenospermia by 44%, 32%, and 45%, respectively. By contrast, CuZn-SOD activity in spermatozoa lysate was significantly higher in males with oligospermia by 60%. The activity of glutathione peroxidase (GPx) in seminal plasma was also significantly higher in males with oligospermia and oligoasthenospermia by 56% and 78%, respectively. The level of malondialdehyde (MDA) in seminal plasma was significantly higher in males with asthenospermia than in the control group by 12%. By contrast, the level of MDA in spermatozoa lysate was significantly lower in males with oligospermia, asthenospermia, and oligoasthenospermia by 26%, 20%, and 26%, respectively. The level of interleukin- (IL-) 8 in seminal plasma was significantly higher in males with asthenospermia and oligoasthenospermia by 64% and 67%, respectively. Abnormalities in spermogram, such as oligospermia, asthenospermia, and oligoasthenospermia, may be related to a decreased activity of Mn-SOD in spermatozoa and increased levels of chemokines in seminal plasma.
Topics: Adult; Antioxidants; Chemokines; Cytokines; Humans; Infertility, Male; Male
PubMed: 30116493
DOI: 10.1155/2018/8354747 -
Fertility and Sterility Feb 2021
Topics: Azoospermia; Humans; Male; Oligospermia; Sperm Injections, Intracytoplasmic
PubMed: 33039129
DOI: 10.1016/j.fertnstert.2020.09.130 -
Reviews in Urology 2020Transwomen may elect to pursue fertility preservation prior beginning hormonal treatment or proceeding with gender-affirming surgery. To date, there has been little... (Review)
Review
Transwomen may elect to pursue fertility preservation prior beginning hormonal treatment or proceeding with gender-affirming surgery. To date, there has been little research specifically investigating factors influencing fertility and preservation thereof among transwomen. Here, we review the case of a transwoman who engaged in genital tucking behavior presenting with severe oligospermia, and we review the literature regarding transgender fertility preservation and the role of the heat stress hypothesis with regards to this common behavior.
PubMed: 33927575
DOI: No ID Found -
Translational Andrology and Urology Mar 2021The human Y-chromosome contains genetic material responsible for normal testis development and spermatogenesis. The long arm (Yq) of the Y-chromosome has been found to... (Review)
Review
The human Y-chromosome contains genetic material responsible for normal testis development and spermatogenesis. The long arm (Yq) of the Y-chromosome has been found to be susceptible to self-recombination during spermatogenesis predisposing this area to deletions. The incidence of these deletions is estimated to be 1/4,000 in the general population but has been found to be much higher in infertile men. Currently, Y-microdeletions are the second most commonly identified genetic cause of male infertility after Klinefelter syndrome. This has led to testing for these deletions becoming standard practice in men with azoospermia and severe oligospermia. There are three commonly identified Y-microdeletions in infertile males, termed azoospermia factor (AZF) microdeletions AZFa, AZFb and AZFc. With increased understanding and investigation of this genetic basis for infertility a more comprehensive understanding of these deletions has evolved, with several other deletion subtypes being identified. Understanding the genetic basis and pathology behind these Y-microdeletions is essential for any clinician involved in reproductive medicine. In this review we discuss the genetic basis of Y-microdeletions, the various subtypes of deletions, and current technologies available for testing. Our understanding of this issue is evolving in many areas, and in this review we highlight future testing opportunities that may allow us to stratify men with Y-microdeletion associated infertility more accurately.
PubMed: 33850774
DOI: 10.21037/tau-19-599 -
American Journal of Human Genetics Aug 2022Although the evolutionary history of the X chromosome indicates its specialization in male fitness, its role in spermatogenesis has largely been unexplored. Currently...
Although the evolutionary history of the X chromosome indicates its specialization in male fitness, its role in spermatogenesis has largely been unexplored. Currently only three X chromosome genes are considered of moderate-definitive diagnostic value. We aimed to provide a comprehensive analysis of all X chromosome-linked protein-coding genes in 2,354 azoospermic/cryptozoospermic men from four independent cohorts. Genomic data were analyzed and compared with data in normozoospermic control individuals and gnomAD. While updating the clinical significance of known genes, we propose 21 recurrently mutated genes strongly associated with and 34 moderately associated with azoospermia/cryptozoospermia not previously linked to male infertility (novel). The most frequently affected prioritized gene, RBBP7, was found mutated in ten men across all cohorts, and our functional studies in Drosophila support its role in germ stem cell maintenance. Collectively, our study represents a significant step towards the definition of the missing genetic etiology in idiopathic severe spermatogenic failure and significantly reduces the knowledge gap of X-linked genetic causes of azoospermia/cryptozoospermia contributing to the development of future diagnostic gene panels.
Topics: Azoospermia; Humans; Infertility, Male; Male; Oligospermia; Spermatogenesis; X Chromosome
PubMed: 35809576
DOI: 10.1016/j.ajhg.2022.06.007 -
Sensors (Basel, Switzerland) Feb 2023(kinetochore scaffold 1) has attracted much attention as one of the assembly elements of the outer kinetochore, and the functions of its different domains have been...
The Loss-Function of Causes Oligospermia and Asthenospermia in Mice by Affecting the Assembly and Separation of the Spindle through Flow Cytometry and Immunofluorescence.
(kinetochore scaffold 1) has attracted much attention as one of the assembly elements of the outer kinetochore, and the functions of its different domains have been gradually revealed, most of which are associated with cancers, but few links have been made between and male fertility. Here, we first linked to male reproductive health and the loss-function of resulted in oligospermia and asthenospermia in mice (an 86.5% decrease in total sperm number and an 82.4% increase in static sperm number, respectively) through CASA (computer-aided sperm analysis). Moreover, we introduced an ingenious method to pinpoint the abnormal stage in the spermatogenic cycle using flow cytometry combined with immunofluorescence. Results showed that 49.5% haploid sperm was reduced and 53.2% diploid sperm was increased after the function of was lost. Spermatocytes arrest was identified at the meiotic prophase I of spermatogenesis, which was induced by the abnormal assembly and separation of the spindle. In conclusion, we established an association between and male fertility, providing a guide for future genetic counseling regarding oligospermia and asthenospermia, and a powerful method for further exploring spermatogenic dysfunction by utilizing flow cytometry and immunofluorescence.
Topics: Animals; Male; Mice; Asthenozoospermia; Flow Cytometry; Fluorescent Antibody Technique; Meiosis; Oligospermia; Semen; Microtubule-Associated Proteins
PubMed: 36904774
DOI: 10.3390/s23052571 -
Advanced Biomedical Research 2014Despite high expectations of safer, effective, economical, longer acting contraceptives, to date, there are no licensed contraceptive vaccines available in the market.... (Review)
Review
Despite high expectations of safer, effective, economical, longer acting contraceptives, to date, there are no licensed contraceptive vaccines available in the market. Nevertheless, a role for vaccines undoubtedly exists as an aid to birth spacing and as a nonsurgical means of generating sterility. The research concerned in the area so far has been successful on the feline population, with room still for exhaustive studies on humans. The future of contraceptive vaccines holds great promise in terms of comfort, price, efficacy, rare complications, and possibly nonselective action on animal populations as well as on humans. This brief review deals with the basic aspects of immunocontraceptives along with the efforts done so far. There is a need for further research in aspects involving the rate of evolution of contraception resistance based on genetics, resistance phenotypes, or cross generation effects. Gonadotropin-releasing hormone and luteinizing-hormone have not been investigated in humans, as both reported impotency in animals; the follicle-stimulating hormone has been shown to cause oligospermia; zona pellucida has also not been studied in humans as it causes irreversible oophoritis, while the sperm has the potential for success in humans based on the data from immunoreproductive studies. Even as the position of the human chorionic gonadotropin vaccine looks hopeful, research on other possible targets continue with an eventual aim of discovering a vaccine that is more immunogenically effective.
PubMed: 25590025
DOI: 10.4103/2277-9175.146369 -
Is There an Association Between Dietary Antioxidant Levels and Sperm Parameters in Male Infertility?Cureus Aug 2023Oxidative stress is known as a mechanism underlying male infertility; it is defined as an imbalance between pro-oxidants and antioxidants leading to DNA damage,...
INTRODUCTION
Oxidative stress is known as a mechanism underlying male infertility; it is defined as an imbalance between pro-oxidants and antioxidants leading to DNA damage, peroxidation of plasma membrane lipids, and protein oxidation. This study was conducted to investigate the relationship between total antioxidant capacity and sperm parameters in male infertility.
METHODS
A total of 187 men with infertility (asthenospermia group (n=51), oligospermia group (n=40), and control group (n=96) were included in the current study. The following risk factors were recorded: age, sperm volume, sperm motility, hormone levels, and dietary antioxidant content.
RESULTS
Demographic parameters and hormone levels of cases showed no statistically significant difference between groups (p > 0.05). Semen volume, motility, vitamin A, retinol, vitamin D, and vitamin C levels were statistically significantly lower in the asthenospermia and oligospermia groups (p < 0.05). According to the logistic regression model, lower vitamin A, retinol, vitamin D, and vitamin C levels were risk factors for poor sperm outcomes (p < 0.001). Conclusıon: Male infertility with poor sperm outcomes should have an assessment of antioxidant capacity and nutritional specialization including food high in antioxidants could improve sperm parameters in asthenospermia and oligospermia and it could be used for therapeutic opportunities.
PubMed: 37649928
DOI: 10.7759/cureus.44339 -
The World Journal of Men's Health Jan 2024Augmented adiposity may negatively impact sexual sphere through its metabolic effects and its detrimental impact on reproductive hormones. Moreover, a dysregulated...
PURPOSE
Augmented adiposity may negatively impact sexual sphere through its metabolic effects and its detrimental impact on reproductive hormones. Moreover, a dysregulated metabolic pathway may promote apoptosis among spermatogenic cells. Based on these premises, a relation between weights loss and ameliorate semen parameters seems beneficial. To investigate if physical activity may affect semen parameters and fertility rate, a systematic literature search on major dataset has been performed.
MATERIALS AND METHODS
The search terms included: "Assisted reproduction therapies," "fertility," "semen parameters," "sperm parameters," and "physical activity." This analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines and it was registered on PROSPERO (CRD42023384471). A total of 47 studies have been identified; 1 reference has been eliminated after duplication check. After preliminary screening 32 papers have been excluded. Considering the exclusion criteria, 15 full-text articles were evaluated for eligibility. After a full-text review, six studies published during a span of eight years (2014-2022) have been included in the meta-analysis. Semen parameters, pregnancy and birth rates were investigated. The revised Cochrane risk of bias tool (Rob2) has been used to check the risk of bias.
RESULTS
The number of patients enrolled in studies ranges from 17 to 521; in the end, a total of 1,637 patients have been enrolled in the study. Fertility parameters investigated were semen quality parameters and pregnancy rates and live births. A statistically significant relationship between physical exercise and sperm concentration (p=0.02), total sperm motility (p<0.01), total sperm count (p<0.01), normal morphology (p<0.01) has been established. Moreover, the study registered a statistically significant association within physical activity and total pregnancy rate (p<0.01) and live birth rate (p<0.01).
CONCLUSIONS
We demonstrated that physical activity is significantly associated with amelioration of semen parameters and may be crucial in improving or even reverting male infertility.
PubMed: 38164031
DOI: 10.5534/wjmh.230106