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1.
Front Endocrinol (Lausanne) ; 15: 1392917, 2024.
Article in English | MEDLINE | ID: mdl-38966220

ABSTRACT

Biogenic amines are signaling molecules with multiple roles in the central nervous system and in peripheral organs, including the gonads. A series of studies indicated that these molecules, their biosynthetic enzymes and their receptors are present in the testis and that they are involved in the regulation of male reproductive physiology and/or pathology. This mini-review aims to summarize the current knowledge in this field and to pinpoint existing research gaps. We suggest that the widespread clinical use of pharmacological agonists/antagonists of these signaling molecules, calls for new investigations in this area. They are necessary to evaluate the relevance of biogenic amines for human male fertility and infertility, as well as the potential value of at least one of them as an anti-aging compound in the testis.


Subject(s)
Biogenic Amines , Testis , Humans , Biogenic Amines/metabolism , Male , Testis/metabolism , Animals , Signal Transduction , Infertility, Male/metabolism
2.
Reprod Fertil Dev ; 362024 Jul.
Article in English | MEDLINE | ID: mdl-38968399

ABSTRACT

Context In recent years, the COVID-19 pandemic became a threat to human health and induced global concern. The SARS-CoV-2 virus causes various disorders in the body's systems, and the reproductive system is no exception. Further, the rate of infertile couples is increasing and part of this is related to male infertility. Aims The aim of the present study was to investigate the impacts of COVID-19 infection history on semen quality in men referred to public and private infertility centres. Methods In this research, patients were divided into two groups: 88 men with a history of COVID-19 (Covid+) and 51 men without (Covid-). After semen collection, sperm parameters, fertilisation rate and oxidative stress were investigated. Key results Sperms with normal morphology and mature chromatin in patients with COVID-19 infection history decreased, and seminal oxidative stress and sperm DNA fragmentation were increased; moreover, the fertilisation rate in the Covid+ group decreased in compare to the Covid- group. Conclusion COVID-19 infection increases oxidative stress in the semen, so has a negative effect on some sperm parameters and fertilisation rate. Implications COVID-19 infection impairs semen quality by increasing in oxidative stress, thus reducing the fertility potential.


Subject(s)
COVID-19 , DNA Fragmentation , Infertility, Male , Oxidative Stress , Semen Analysis , Semen , Spermatozoa , Humans , Male , COVID-19/complications , COVID-19/epidemiology , COVID-19/virology , Adult , Infertility, Male/virology , Infertility, Male/epidemiology , Oxidative Stress/physiology , Spermatozoa/virology , Spermatozoa/pathology , Semen/virology , SARS-CoV-2 , Fertility Clinics , Sperm Motility
3.
Hinyokika Kiyo ; 70(6): 167-171, 2024 Jun.
Article in Japanese | MEDLINE | ID: mdl-38967029

ABSTRACT

A 42-year-old man visited our hospital complaining of secondary infertility. An abdominal ultrasonography screening incidentally revealed a protruding lesion in the bladder. As the lesion extended from the prostatic urethra and bladder neck, there was a possibility of ejaculation dysfunction after resection of the lesion. Therefore, with the patient's informed consent, sperm cryopreservation was conducted for fertility preservation, and subsequently histological examination was performed by partial transurethral resection of bladder tumor. The pathological findings were proliferative cystitis including all three subtypes (glandularis, cystica, and papillary). Cyclooxygenase-2 immunostaining was positive in cytoplasm; weakly positive in cystic and papillary lesions, and strongly positive in glandular lesions. According to a literature review of massive proliferative cystitis, the patient was the 77th case in Japan. Novel postoperative immunological pharmacotherapies with cyclooxygenase-2 inhibitors have been introduced in recent years.


Subject(s)
Cystitis , Humans , Male , Adult , Cystitis/diagnostic imaging , Cystitis/pathology , Infertility, Male/etiology
4.
Clin Transl Sci ; 17(7): e13866, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38965809

ABSTRACT

Rising cure rates in pediatric cancer patients warrants an increased attention toward the long-term consequences of the diagnosis and treatment in survivors. Chemotherapeutic agents can be gonadotoxic, rendering them at risk for infertility post-survival. While semen cryopreservation is an option that can be provided for most (post)pubertal boys before treatment, this is unfortunately not an option prepubertal in age, simply due to the lack of spermatogenesis. Over the last couple of years, studies have thus focused on better understanding the testis niche in response to various chemotherapeutic agents that are commonly administered and their direct and indirect impact on the germ cell populations. These are generally compounds that have a high risk of infertility and have been classified into risk categories in curated fertility guidelines. However, with it comes the lack of evidence and the challenge of using informative models and conditions most reflective of the physiological scenario, in short, the appropriate study designs for clinically relevant outcomes. Besides, the exact mechanism(s) of action for many of these "risk" compounds as well as other agents is unclear. Understanding their behavior and effect on the testis niche will pave the way for incorporating new strategies to ultimately combat infertility. Of the various drug classes, alkylating agents pose the highest risk of gonadotoxicity as per previously established studies as well as risk stratification guidelines. Therefore, this review will summarize the findings in the field of male fertility concerning gonadotoxicity of akylating agents as a result of chemotherapy exposure.


Subject(s)
Antineoplastic Agents, Alkylating , Testis , Humans , Male , Testis/drug effects , Child , Antineoplastic Agents, Alkylating/adverse effects , Antineoplastic Agents, Alkylating/administration & dosage , Infertility, Male/chemically induced , Infertility, Male/etiology , Infertility, Male/diagnosis , Animals , Spermatogenesis/drug effects , Spermatogenesis/radiation effects , Neoplasms/drug therapy , Puberty/drug effects , Puberty/physiology , Alkylating Agents/adverse effects , Alkylating Agents/administration & dosage
5.
Nat Commun ; 15(1): 5582, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38961093

ABSTRACT

Male infertility is a major public health concern globally with unknown etiology in approximately half of cases. The decline in total sperm count over the past four decades and the parallel increase in childhood obesity may suggest an association between these two conditions. Here, we review the molecular mechanisms through which obesity during childhood and adolescence may impair future testicular function. Several mechanisms occurring in obesity can interfere with the delicate metabolic processes taking place at the testicular level during childhood and adolescence, providing the molecular substrate to hypothesize a causal relationship between childhood obesity and the risk of low sperm counts in adulthood.


Subject(s)
Sertoli Cells , Spermatogonia , Male , Humans , Sertoli Cells/metabolism , Child , Adolescent , Spermatogonia/metabolism , Infertility, Male/metabolism , Metabolic Diseases/metabolism , Spermatogenesis , Pediatric Obesity/metabolism , Testis/metabolism , Testis/growth & development , Animals , Sperm Count
6.
Development ; 151(13)2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38953252

ABSTRACT

Spermatogonial stem cell (SSC) self-renewal and differentiation provide foundational support for long-term, steady-state spermatogenesis in mammals. Here, we have investigated the essential role of RNA exosome associated DIS3 ribonuclease in maintaining spermatogonial homeostasis and facilitating germ cell differentiation. We have established male germ-cell Dis3 conditional knockout (cKO) mice in which the first and subsequent waves of spermatogenesis are disrupted. This leads to a Sertoli cell-only phenotype and sterility in adult male mice. Bulk RNA-seq documents that Dis3 deficiency partially abolishes RNA degradation and causes significant increases in the abundance of transcripts. This also includes pervasively transcribed PROMoter uPstream Transcripts (PROMPTs), which accumulate robustly in Dis3 cKO testes. In addition, scRNA-seq analysis indicates that Dis3 deficiency in spermatogonia significantly disrupts RNA metabolism and gene expression, and impairs early germline cell development. Overall, we document that exosome-associated DIS3 ribonuclease plays crucial roles in maintaining early male germ cell lineage in mice.


Subject(s)
Fertility , Mice, Knockout , Spermatogenesis , Spermatogonia , Testis , Animals , Male , Spermatogenesis/genetics , Spermatogenesis/physiology , Mice , Fertility/genetics , Testis/metabolism , Spermatogonia/metabolism , Spermatogonia/cytology , Sertoli Cells/metabolism , Cell Differentiation , Exosome Multienzyme Ribonuclease Complex/metabolism , Exosome Multienzyme Ribonuclease Complex/genetics , Exosomes/metabolism , RNA Stability/genetics , Infertility, Male/genetics
7.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(3): 527-534, 2024 May 20.
Article in Chinese | MEDLINE | ID: mdl-38948273

ABSTRACT

Infertility affects an estimated 10 to 15 percent of couples worldwide, with approximately half of the cases attributed to male-related issues. Most men diagnosed with infertility exhibit symptoms such as oligospermia, asthenospermia, azoospermia, and compromised sperm quality. Spermatogenesis is a complex and tightly coordinated process of germ cell differentiation, precisely regulated at transcriptional, posttranscriptional, and translational levels to ensure stage-specific gene expression during the development of spermatogenic cells and normal spermiogenesis. N6-methyladenosine (m6A) stands out as the most prevalent modification on eukaryotic mRNA, playing pivotal roles in various biological processes, including mRNA splicing, transportation, and translation. RNA methylation modification is a dynamic and reversible process primarily mediated by "writers", removed by "erasers", and recognized by "readers". In mammals, the aberrant methylation modification of m6A on mRNA is associated with a variety of diseases, including male infertility. However, the precise involvement of disrupted m6A modification in the pathogenesis of human male infertility remains unresolved. Intriguingly, a significant correlation has been found between the expression levels of m6A regulators in the testis and the severity of sperm concentration, motility, and morphology. Aberrant expression patterns of m6A regulatory proteins have been detected in anomalous human semen samples, including those of oligospermia, asthenozoospermia, and azoospermia. Furthermore, the examination of both sperm samples and testicular tissues revealed abnormal mRNA m6A modification, leading to reduced sperm motility and concentration in infertile men. Consequently, it is hypothesized that dysregulation of m6A modification might serve as an integral link in the mechanism of male infertility. This paper presents a comprehensive review of the recent discoveries regarding the spatial and temporal expression dynamics of m6A regulators in testicular tissues and the correlation between deregulated m6A regulators and human male infertility. Previous studies predominantly utilized constitutive or conditional knockout animal models for testicular phenotypic investigations. However, gene suppression in additional tissues could potentially influence the testis in constitutive knockout models. Furthermore, considering the compromised spermatogenesis observed in constitutive animals, distinguishing between the indirect effects of gene depletion on testicular development and its direct impact on the spermatogenic process is challenging, due to their intricate relationship. Such confounding factors might compromise the validity of the findings. To address this challenge, an inducible and conditional gene knockout model may serve as a superior approach. To date, nearly all reported studies have concentrated solely on the level changes of m6A and its regulators in germs cells, while the understanding of the function of m6A modification in testicular somatic cells remains limited. Testicular somatic cells, including peritubular myoid cells, Sertoli cells, and Leydig cells, play indispensable roles during spermatogenesis. Hence, comprehensive exploration of m6A modification within these cells as an additional crucial regulatory mechanism is warranted. In addition, exploration into the presence of unique methylation mechanisms or m6A regulatory factors within the testes is warranted. To elucidate the role of m6A modification in germ cells and testicular somatic cells, detailed experimental strategies need to be implemented. Among them, manipulation of the levels of key enzymes involved in m6A methylation and demethylation might be the most effective approach. Moreover, comprehensive analysis of the gene expression profiles involved in various signaling pathways, such as Wnt/ß-catenin, Ras/MAPK, and Hippo, in m6A-modified germ cells and testicular somatic cells can provide more insight into its regulatory role in the spermatogenesis process. Further research in this area could provide valuable insights for developing innovative strategies to treat male infertility. Finally, considering the mitigation impact of m6A imbalance regulation on disease, investigation concerning whether restoring the equilibrium of m6A modification regulation can restore normal spermatogenesis function is essential, potentially elucidating the pivotal clinical significance of m6A modulation in male infertility.


Subject(s)
Adenosine , Infertility, Male , Spermatogenesis , Male , Humans , Adenosine/analogs & derivatives , Adenosine/metabolism , Spermatogenesis/genetics , Infertility, Male/genetics , Infertility, Male/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Methylation , Animals , Methyltransferases/metabolism , Methyltransferases/genetics , Spermatozoa/metabolism , Testis/metabolism
8.
BMC Public Health ; 24(1): 1805, 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38971742

ABSTRACT

BACKGROUND: Infertility in men causes problems in various aspects of their lives, including personal, family and social life. One of the most important of these problems is anxiety. Anxiety in infertile men can affect their health, quality of life, and response to treatment, highlighting the significance of anxiety in these men. Thus, this systematic review and meta-analysis was conducted to investigate the prevalence of anxiety symptoms in infertile men. METHODS: To conduct this review study, two researchers independently searched international databases such as PubMed, Cochrane Library, Web of sciences, Scopus, PsyINFO, and the Google scholar search engine in English without considering any time limit until January 2, 2024. Keywords such as "anxiety," "infertility," "prevalence," and "epidemiology" were used, taking into account the specific search method of each database. Using the Newcastle-Ottawa Scale (NOS), the quality of the articles was evaluated by two researchers independently. RESULTS: In the systematic part of the study, 27 studies were included, and given the variety of measurement tools (8 different tools) used to investigate anxiety symptoms in infertile men, 24 studies were analyzed in five subgroups of tools. The pooled prevalence of anxiety symptoms in infertile men was 21.37% (95% CI: 15.73-27.02). The lowest and highest prevalence of anxiety in infertile men were related to the Beck anxiety inventory (BAI) and Depression Anxiety Stress Scales (DASS), accounting for 7.08% (95% CI: 3.27-10.90) and 34.90% (95%CI: 28.90-40.90) values respectively. This prevalence was 19.80% (95%CI: 9.01-30.59) for the Hospital Anxiety and Depression Scale (HADS), 30.06% (95%CI: 18.59-41.52) for the Spielberger Trait Anxiety Inventory (STAI-T), and 18.52% (95%CI: 7.76-29.29) for the Self-Rating Anxiety Scale (SAS). CONCLUSION: The results of this systematic review and meta-analysis indicated that the prevalence of anxiety symptoms in infertile men requires special attention to healthcare planning. The healthcare system of different countries should evaluate the symptoms of anxiety in infertile men and take appropriate measures to reduce them according to the culture of the countries. It is recommended that all infertile couples be assessed for anxiety symptoms using a standardized tool during their initial evaluation.


Subject(s)
Anxiety , Infertility, Male , Humans , Male , Anxiety/epidemiology , Prevalence , Infertility, Male/epidemiology , Infertility, Male/psychology , Quality of Life
9.
Cells ; 13(12)2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38920681

ABSTRACT

Odad3 gene loss-of-function mutation leads to Primary Ciliary Dyskinesia (PCD), a disease caused by motile cilia dysfunction. Previously, we demonstrated that knockout of the Odad3 gene in mice replicates several features of PCD, such as hydrocephalus, defects in left-right body symmetry, and male infertility, with a complete absence of sperm in the reproductive tract. The majority of Odad3 knockout animals die before sexual maturation due to severe hydrocephalus and failure to thrive, which precludes fertility studies. Here, we performed the expression analysis of the Odad3 gene during gonad development and in adult testes. We showed that Odad3 starts its expression during the first wave of spermatogenesis, specifically at the meiotic stage, and that its expression is restricted to the germ cells in the adult testes, suggesting that Odad3 plays a role in spermatozoa formation. Subsequently, we conditionally deleted the Odad3 gene in adult males and demonstrated that even partial ablation of the Odad3 gene leads to asthenoteratozoospermia with multiple morphological abnormalities of sperm flagella (MMAF) in mice. The analysis of the seminiferous tubules in Odad3-deficient mice revealed defects in spermatogenesis with accumulation of seminiferous tubules at the spermiogenesis and spermiation phases. Furthermore, analysis of fertility in heterozygous Odad3+/- knockout mice revealed a reduction in sperm count and motility as well as abnormal sperm morphology. Additionally, Odad3+/- males exhibited a shorter fertile lifespan. Overall, these results suggest the important role of Odad3 and Odad3 gene dosage in male fertility. These findings may have an impact on the genetic and fertility counseling practice of PCD patients carrying Odad3 loss-of-function mutations.


Subject(s)
Fertility , Mice, Knockout , Spermatogenesis , Spermatozoa , Animals , Male , Spermatogenesis/genetics , Fertility/genetics , Mice , Spermatozoa/metabolism , Testis/metabolism , Testis/pathology , Infertility, Male/genetics , Infertility, Male/pathology , Mice, Inbred C57BL
10.
Reprod Fertil Dev ; 362024 Jun.
Article in English | MEDLINE | ID: mdl-38902908

ABSTRACT

Intracytoplasmic sperm injection (ICSI) is an assisted reproductive technology for treatment of severe male infertility introduced into clinical practice in 1992. This review provides a brief history of the development of ICSI by acknowledging major developments in the field. The review addresses key developments in pre-clinical and early studies, how ICSI compares with in vitro fertilisation, long-term consequences, how the mechanistic approach to ICSI has changed in both manual and semi-automated approaches, and how sperm selection procedures are integrated into ICSI. From the beginnings using animal models in the 1960-1970s, the development of ICSI is a remarkable and transformative success story. Indeed, its broad use (70% of cycles globally) exceeds the need required for treating infertile males, and this remains a controversial issue. There remain questions around the long-term health impacts of ICSI. Furthermore, advances in automation of the ICSI procedure are occurring. An estimated 6million children have been born from the ICSI procedure. With further automation of sperm selection technologies, coupled with automation of the injection procedure, it is likely that the proportion of children born from ICSI will further increase.


Subject(s)
Sperm Injections, Intracytoplasmic , Sperm Injections, Intracytoplasmic/history , Sperm Injections, Intracytoplasmic/methods , History, 20th Century , Humans , Male , History, 21st Century , Animals , Female , Infertility, Male/therapy , Infertility, Male/history , Pregnancy
11.
BMC Urol ; 24(1): 123, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38867229

ABSTRACT

BACKGROUND: Male infertility has become a global health problem, and genetic factors are one of the essential causes. Y chromosome microdeletion is the leading genetic factor cause of male infertility. The objective of this study is to investigate the correlation between male infertility and Y chromosome microdeletions in Hainan, the sole tropical island province of China. METHODS: We analyzed the semen of 897 infertile men from Hainan in this study. Semen analysis was measured according to WHO criteria by professionals at the Department of Reproductive Medicine, the First Affiliated Hospital of Hainan Medical University, where samples were collected. Y chromosome AZF microdeletions were confirmed by detecting six STS markers using multiple polymerase chain reactions on peripheral blood DNA. The levels of reproductive hormones, including FSH, LH, PRL, T, and E2, were quantified using the enzyme-linked immunosorbent assay (ELISA). RESULTS: The incidence of Y chromosome microdeletion in Hainan infertile men was 7.13%. The occurrence rate of Y chromosome microdeletion was 6.69% (34/508) in the oligozoospermia group and 7.71% (30/389) in the azoospermia group. The deletion of various types in the AZF subregion was observed in the group with azoospermia, whereas no AZFb deletion was detected in the oligozoospermia group. Among all patients with microdeletions, the deletion rate of the AZFc region was the higher at 68.75% (44 out of 64), followed by a deletion rate of 6.25% (4 out of 64) for the AZFa region and a deletion rate of 4.69% (3 out of 64) for the AZFb region. The deletion rate of the AZFa region was significantly higher in patients with azoospermia than in patients with oligozoospermia (0.51% vs. 0.39%, p < 0.001). In comparison, the deletion rate of the AZFc region was significantly higher in patients with oligozoospermia (3.08% vs. 6.30%, p < 0.001). Additionally, the AZFb + c subregion association deletion was observed in the highest proportion among all patients (0.89%, 8/897), followed by AZFa + b + c deletion (0.56%, 5/897), and exclusively occurred in patients with azoospermia. Hormone analysis revealed FSH (21.63 ± 2.01 U/L vs. 10.15 ± 0.96 U/L, p = 0.001), LH (8.96 ± 0.90 U/L vs. 4.58 ± 0.42 U/L, p < 0.001) and PRL (263.45 ± 21.84 mIU/L vs. 170.76 ± 17.10 mIU/L, p = 0.002) were significantly increased in azoospermia patients with microdeletions. Still, P and E2 levels were not significantly different between the two groups. CONCLUSIONS: The incidence of AZF microdeletion can reach 7.13% in infertile men in Hainan province, and the deletion of the AZFc subregion is the highest. Although the Y chromosome microdeletion rate is distinct in different regions or populations, the regions mentioned above of the Y chromosome may serve an indispensable role in regulating spermatogenesis. The analysis of Y chromosome microdeletion plays a crucial role in the clinical assessment and diagnosis of male infertility.


Subject(s)
Chromosome Deletion , Chromosomes, Human, Y , Infertility, Male , Reproductive Techniques, Assisted , Sex Chromosome Aberrations , Sex Chromosome Disorders of Sex Development , Humans , Male , Infertility, Male/genetics , Infertility, Male/blood , Infertility, Male/epidemiology , China/epidemiology , Adult , Sex Chromosome Disorders of Sex Development/blood , Sex Chromosome Disorders of Sex Development/genetics , Sex Chromosome Disorders of Sex Development/epidemiology , Luteinizing Hormone/blood , Follicle Stimulating Hormone/blood , Azoospermia/genetics , Azoospermia/blood , Prolactin/blood , Oligospermia/genetics , Oligospermia/blood , Testosterone/blood , Estradiol/blood , Semen Analysis
12.
Reproduction ; 168(2)2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38847770

ABSTRACT

Over the past 50 years, there has been a concerning decline in male reproductive health and an increase in male infertility which is now recognised as a major health concern globally. While male infertility can be linked to some genetic and lifestyle factors, these do not fully explain the rate of declining male reproductive health. Increasing evidence from human and animal studies suggests that exposure to chemicals found ubiquitously in the environment may in part play a role. Many studies on chemical exposure, however, have assessed the effects of exposure to individual environmental chemicals (ECs), usually at levels not relevant to everyday human exposure. There is a need for study models which reflect the 'real-life' nature of EC exposure. One such model is the biosolids-treated pasture (BTP) sheep model which utilises biosolids application to agricultural land to examine the effects of exposure to low-level mixtures of chemicals. Biosolids are the by-product of the treatment of wastewater from industrial and domestic sources and so their composition is reflective of the ECs to which humans are exposed. Over the last 20 years, the BTP sheep model has published multiple effects on offspring physiology including consistent effects on the male reproductive system in fetal, neonatal, juvenile, and adult offspring. This review focuses on the evidence from these studies which strongly suggests that low-level EC exposure during gestation can alter several components of the male reproductive system and highlights the BTP model as a more relevant model to study real-life EC exposure effects.


Subject(s)
Environmental Exposure , Reproduction , Male , Animals , Reproduction/drug effects , Humans , Environmental Exposure/adverse effects , Infertility, Male/chemically induced , Infertility, Male/etiology , Sheep , Female , Pregnancy , Environmental Pollutants/toxicity , Sewage/adverse effects , Prenatal Exposure Delayed Effects
13.
J Basic Clin Physiol Pharmacol ; 35(3): 105-110, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38830206

ABSTRACT

The process-of-male reproduction is intricate, and various medical conditions-have the potential to disrupt spermatogenesis. Moreover, infertility in males can serve as an indicator of-potential future health issue. Numerous conditions with systemic implications have been identified, encompassing genetic factors (such as Klinefelter Syndrome), obesity, psychological stress, environmental factors, and others. Consequently, infertility assessment-presents an opportunity for comprehensive health counseling, extending-beyond discussions about reproductive goals. Furthermore, male infertility has been suggested as a harbinger of future health problems, as poor semen quality and a diagnosis of-male infertility are associated with an increased risk of hypogonadism, cardiometabolic disorders, cancer, and even mortality. This review explores the existing-literature on the relationship between systemic illnesses and male fertility, impacting both clinical-outcomes and semen parameters. The majority of the literature analyzed, which compared gonadal function with genetic, chronic, infectious or tumoral diseases, confirm the association between overall male health and infertility.


Subject(s)
Infertility, Male , Male , Humans , Infertility, Male/physiopathology , Spermatogenesis/physiology , Semen Analysis/methods , Hypogonadism/physiopathology , Men's Health , Animals
14.
Proc Natl Acad Sci U S A ; 121(27): e2312456121, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38917000

ABSTRACT

Controlling the principal African malaria vector, the mosquito Anopheles gambiae, is considered essential to curtail malaria transmission. However, existing vector control technologies rely on insecticides, which are becoming increasingly ineffective. Sterile insect technique (SIT) is a powerful suppression approach that has successfully eradicated a number of insect pests, yet the A. gambiae toolkit lacks the requisite technologies for its implementation. SIT relies on iterative mass releases of nonbiting, nondriving, sterile males which seek out and mate with monandrous wild females. Once mated, females are permanently sterilized due to mating-induced refractoriness, which results in population suppression of the subsequent generation. However, sterilization by traditional methods renders males unfit, making the creation of precise genetic sterilization methods imperative. Here, we introduce a vector control technology termed precision-guided sterile insect technique (pgSIT), in A. gambiae for inducible, programmed male sterilization and female elimination for wide-scale use in SIT campaigns. Using a binary CRISPR strategy, we cross separate engineered Cas9 and gRNA strains to disrupt male-fertility and female-essential genes, yielding >99.5% male sterility and >99.9% female lethality in hybrid progeny. We demonstrate that these genetically sterilized males have good longevity, are able to induce sustained population suppression in cage trials, and are predicted to eliminate wild A. gambiae populations using mathematical models, making them ideal candidates for release. This work provides a valuable addition to the malaria genetic biocontrol toolkit, enabling scalable SIT-like confinable, species-specific, and safe suppression in the species.


Subject(s)
Anopheles , Malaria , Mosquito Control , Mosquito Vectors , Animals , Male , Anopheles/genetics , Anopheles/physiology , Mosquito Vectors/genetics , Mosquito Vectors/parasitology , Malaria/transmission , Malaria/prevention & control , Female , Mosquito Control/methods , Infertility, Male/genetics , CRISPR-Cas Systems
15.
Int J Nanomedicine ; 19: 5095-5108, 2024.
Article in English | MEDLINE | ID: mdl-38836008

ABSTRACT

Sperm quality is declining dramatically during the past decades. Male infertility has been a serious health and social problem. The sperm cell driven biohybrid nanorobot opens a new era for automated and precise assisted reproduction. Therefore, it is urgent and necessary to conduct an updated review and perspective from the viewpoints of the researchers and clinicians in the field of reproductive medicine. In the present review, we first update the current classification, design, control and applications of various spermbots. Then, by a comprehensive summary of the functional features of sperm cells, the journey of sperms to the oocyte, and sperm-related dysfunctions, we provide a systematic guidance to further improve the design of spermbots. Focusing on the translation of spermbots into clinical practice, we point out that the main challenges are biocompatibility, effectiveness, and ethical issues. Considering the special requirements of assisted reproduction, we also propose the three laws for the clinical usage of spermbots: good genetics, gentle operation and no contamination. Finally, a three-step roadmap is proposed to achieve the goal of clinical translation. We believe that spermbot-based treatments can be validated and approved for in vitro clinical usage in the near future. However, multi-center and multi-disciplinary collaborations are needed to further promote the translation of spermbots into in vivo clinical applications.


Subject(s)
Reproductive Techniques, Assisted , Spermatozoa , Humans , Spermatozoa/physiology , Male , Infertility, Male/therapy , Animals , Female
16.
Syst Biol Reprod Med ; 70(1): 139-149, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38870367

ABSTRACT

The World Health Organization has considered the infertility as an international public health problem. Infertility affect nearly 1 in 7 couples and male component contributes to 50% of infertility cases. There is a clear link between male infertility and some cancers such as testicular germ cell, prostate and colon cancers. Two possibilities support this finding: 1) Cancer treatments can affect the fertility factors 2) Genetic profile of infertility genes have been altered in cancer patients. Although the previously published researches have mostly focused on the first factor, no article has yet confirmed the role of genetic factors. In this in silico study, we collected the large number of genes (n = 17703) involved in infertility. These genes were collected from NGS panel tests of male infertility and comprehensive literature review or online data base. The Prostate Adenocarcinoma genomic and transcriptomics raw data were downloaded from the cBioPortal Cancer dataset. This included with 494 patients of Prostate Cancer with 494 mutation data, 489 with CNA and 493 with RNA seqV2 data. TCGA RNA-Seq raw data was extracted in R using the cgdsr extension package with a threshold of ±2 relative to normal samples. The observed data showed that male infertility genes have been distributed through the human genome. Among the 17703 analyzed genes of this study, the genomic profile of three genes including OR9Q1, H4C6 and PSG7 were changed approximately in 100% of (n = 493) patients. In most of patients (>98%), genetic alteration was related to change in gene expression. In conclusion, this study showed that the genomic and transcriptomics patterns of some male-infertility genes are notably altered in patients of prostate cancer and suggested a possible role of genetic factors in occurrence of infertility in cancer patients. Our information can be used as a source for the design of genetic database of male-infertility.


Subject(s)
Genomics , Infertility, Male , Prostatic Neoplasms , Transcriptome , Male , Humans , Prostatic Neoplasms/genetics , Infertility, Male/genetics , Gene Expression Profiling , Computer Simulation , Mutation , Databases, Genetic
17.
Proc Biol Sci ; 291(2025): 20240483, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38889778

ABSTRACT

Interspecies hybrid sterility has been extensively studied, especially in the genus Drosophila. Hybrid sterility is more often found in the heterogametic (XY or ZW) sex, a trend called Haldane's rule. Although this phenomenon is pervasive, identification of a common genetic mechanism remains elusive, with modest support found for a range of potential theories. Here, we identify a single precise morphological phenotype, which we call 'needle-eye sperm', that is associated with hybrid sterility in three separate species pairs that span the Drosophila genus. The nature of the phenotype indicates a common point of meiotic failure in sterile hybrid males. We used 10 generations of backcross selection paired with whole-genome pooled sequencing to genetically map the regions underlying the needle-eye (NE) sperm phenotype. Surprisingly, the sterility phenotype was present in ~50% of males even after 10 generations of backcrossing, and only a single region of the X chromosome was associated with sterility in one direction of backcross. Owing to the common phenotype among sterile male hybrids, and the strong effect of individual loci, further exploration of these findings may identify a universal mechanism for the evolution of hybrid sterility.


Subject(s)
Drosophila , Infertility, Male , Phenotype , Spermatozoa , Animals , Male , Drosophila/genetics , Drosophila/physiology , Spermatozoa/physiology , Infertility, Male/genetics , Hybridization, Genetic
18.
Sensors (Basel) ; 24(11)2024 May 28.
Article in English | MEDLINE | ID: mdl-38894284

ABSTRACT

Male infertility is a global health issue, with 40-50% attributed to sperm abnormalities. The subjectivity and irreproducibility of existing detection methods pose challenges to sperm assessment, making the design of automated semen analysis algorithms crucial for enhancing the reliability of sperm evaluations. This paper proposes a comprehensive sperm tracking algorithm (Sperm YOLOv8E-TrackEVD) that combines an enhanced YOLOv8 small object detection algorithm (SpermYOLOv8-E) with an improved DeepOCSORT tracking algorithm (SpermTrack-EVD) to detect human sperm in a microscopic field of view and track healthy sperm in a sample in a short period effectively. Firstly, we trained the improved YOLOv8 model on the VISEM-Tracking dataset for accurate sperm detection. To enhance the detection of small sperm objects, we introduced an attention mechanism, added a small object detection layer, and integrated the SPDConv and Detect_DyHead modules. Furthermore, we used a new distance metric method and chose IoU loss calculation. Ultimately, we achieved a 1.3% increase in precision, a 1.4% increase in recall rate, and a 2.0% improvement in mAP@0.5:0.95. We applied SpermYOLOv8-E combined with SpermTrack-EVD for sperm tracking. On the VISEM-Tracking dataset, we achieved 74.303% HOTA and 71.167% MOTA. These results show the effectiveness of the designed Sperm YOLOv8E-TrackEVD approach in sperm tracking scenarios.


Subject(s)
Algorithms , Semen Analysis , Spermatozoa , Male , Humans , Spermatozoa/physiology , Spermatozoa/cytology , Semen Analysis/methods , Infertility, Male/diagnosis , Image Processing, Computer-Assisted/methods
19.
Syst Biol Reprod Med ; 70(1): 150-163, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38896558

ABSTRACT

The incidence of male infertility (MI) is rising annually. However, the lifestyle and occupational exposure factors contributing to MI remain incompletely understood. This study explored the effects of self-reported lifestyle and occupational exposure factors on semen quality. Among 1060 subjects invited to participate, 826 were eligible. The participants' general characteristics, lifestyle, and occupational exposure factors were collected immediately before or after semen evaluation through an online questionnaire. Initially, univariate analysis was used to investigate the relationship between the abovementioned factors and semen quality. The results indicated significant associations between low semen quality and various factors, including age, BMI, infertility type and duration, abstinence time, semen and sperm parameters, smoking, alcohol consumption, irregular sleep habits, and frequent exposure to high temperatures and chemicals at work (p < 0.05). Then, multivariate analysis was conducted to identify factors independently associated with low semen quality. Adjustment for relevant confounders was achieved by including factors with a p-value < 0.25 from univariate analyses as covariates in the binomial and ordered logistic regression models. The results suggested that alcohol consumption was a positive factor for sperm concentration (odds ratio [OR] = 0.60; 95% confidence interval [CI] = 0.36-0.99; p = 0.045). The groups with a BMI ≥ 24 and <28 kg/m2 showed a significant decrease in sperm progressive motility when compared to the reference group (BMI < 24 kg/m2) (OR = 0.63; 95% CI = 0.46-0.87, p = 0.005). In addition, the groups that drank green tea <1 time/week (OR = 1.52, 95% CI = 1.05-2.2) and 1-4 times/week (OR = 1.61, 95% CI = 1.02-2.54) exhibited significantly increased sperm DFI values compared with the group that drank green tea 5-7 times/week. In conclusion, these findings underscore the importance of maintaining a normal weight and regularly consuming green tea for men.


Subject(s)
Infertility, Male , Life Style , Occupational Exposure , Semen Analysis , Humans , Male , Adult , Occupational Exposure/adverse effects , Cross-Sectional Studies , Infertility, Male/etiology , Infertility, Male/epidemiology , Alcohol Drinking/adverse effects , Risk Factors , Middle Aged , Sperm Motility , Sperm Count
20.
Int J Mol Sci ; 25(11)2024 May 22.
Article in English | MEDLINE | ID: mdl-38891830

ABSTRACT

The dynamic process of Drosophila spermatogenesis involves asymmetric division, mitosis, and meiosis, which ultimately results in the production of mature spermatozoa. Disorders of spermatogenesis can lead to infertility in males. ADAR (adenosine deaminase acting on RNA) mutations in Drosophila cause male infertility, yet the causative factors remain unclear. In this study, immunofluorescence staining was employed to visualize endogenous ADAR proteins and assess protein levels via fluorescence-intensity analysis. In addition, the early differentiation disorders and homeostatic alterations during early spermatogenesis in the testes were examined through quantification of transit-amplifying region length, counting the number of GSCs (germline stem cells), and fertility experiments. Our findings suggest that deletion of ADAR causes testicular tip transit-amplifying cells to accumulate and become infertile in older male Drosophila. By overexpressing ADAR in early germline cells, male infertility can be partially rescued. Transcriptome analysis showed that ADAR maintained early spermatogenesis homeostasis through the bone-morphogenetic-protein (BMP) signaling pathway. Taken together, these findings have the potential to help explore the role of ADAR in early spermatogenesis.


Subject(s)
Adenosine Deaminase , Bone Morphogenetic Proteins , Drosophila Proteins , Drosophila melanogaster , Signal Transduction , Spermatogenesis , Animals , Male , Spermatogenesis/genetics , Drosophila melanogaster/genetics , Drosophila melanogaster/metabolism , Drosophila Proteins/metabolism , Drosophila Proteins/genetics , Adenosine Deaminase/metabolism , Adenosine Deaminase/genetics , Bone Morphogenetic Proteins/metabolism , Bone Morphogenetic Proteins/genetics , Infertility, Male/genetics , Infertility, Male/metabolism , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , Testis/metabolism
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