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Journal of Cellular and Molecular... Oct 2023Primary ciliary dyskinesia (PCD) is a rare autosomal-recessive disease manifested with recurrent infections of respiratory tract and infertility. DNAAF3 is identified as...
Primary ciliary dyskinesia (PCD) is a rare autosomal-recessive disease manifested with recurrent infections of respiratory tract and infertility. DNAAF3 is identified as a novel gene associated with PCD and different mutations in DNAAF3 results in different clinical features of PCD patients, such as situs inversus, sinusitis and bronchiectasis. However, the sperm phenotypic characteristics of PCD males are generally poorly investigated. Our reproductive medicine centre received a case of PCD patient with infertility, who presented with sinusitis, recurrent infections of the lower airway and severe asthenozoospermia; However, no situs inversus was found in the patient. A novel homozygous mutation in DNAAF3(c.551T>A; p.V184E) was identified in the PCD patient by whole-exome sequencing. Subsequent Sanger sequencing further confirmed that the DNAAF3 had a homozygous missense variant in the fifth exon. Transmission electron microscopy and immunostaining analysis of the sperms from the patient showed a complete absence of outer dynein arms and partial absence of inner dynein arms, which resulted in the reduction in sperm motility. However, this infertility was overcome by intracytoplasmic sperm injections, as his wife achieved successful pregnancy. These findings showed that the PCD-associated pathogenic mutation within DNAAF3 also causes severe asthenozoospermia and male infertility ultimately due to sperm flagella axoneme defect in humans. Our study not only contributes to understand the sperm phenotypic characteristics of patients with DNAAF3 mutations but also expands the spectrum of DNAAF3 mutations and may contribute to the genetic diagnosis and therapy for infertile patient with PCD.
PubMed: 37537752
DOI: 10.1111/jcmm.17881 -
Frontiers in Endocrinology 2023In recent years, the quality of male semen has been decreasing, and the number of male infertilities caused by asthenozoospermia is increasing year by year, and the...
INTRODUCTION
In recent years, the quality of male semen has been decreasing, and the number of male infertilities caused by asthenozoospermia is increasing year by year, and the diagnosis and treatment of patients with asthenozoospermia are gradually receiving the attention of the whole society. Due to the unknown etiology and complex pathogenesis, there is no specific treatment for asthenozoospermia. Our previous study found that the administration of chestnut polysaccharide could alter the intestinal microbiota and thus improve the testicular microenvironment, and rescue the impaired spermatogenesis process by enhancing the expression of reproduction-related genes, but its exact metabolome-related repairment mechanism of chestnut polysaccharide is still unclear.
METHODS AND RESULTS
In this study, we studied the blood metabolomic changes of busulfan-induced asthenozoospermia-model mice before and after oral administration of chestnut polysaccharide with the help of metabolome, and screened two key differential metabolites (hydrogen carbonate and palmitic acid) from the set of metabolomic changes; we then analyzed the correlation between several metabolites and between different metabolites and intestinal flora by correlation analysis, and found that palmitic acid in the blood serum of mice after oral administration of chestnut polysaccharide had different degrees of correlation with various metabolites, and palmitic acid level had a significant positive correlation with the abundance of ; finally, we verified the role of palmitic acid in rescuing the damaged spermatogenesis process by using asthenozoospermia-model mice, and screened the key target gene for palmitic acid to play the rescuing effect by integrating the analysis of multiple databases.
DISCUSSION
In conclusion, this study found that chestnut polysaccharide rescued the damaged spermatogenesis in asthenozoospermia-model mice by upregulating palmitic acid level, which will provide theoretical basis and technical support for the use of chestnut polysaccharide in the treatment of asthenozoospermia.
Topics: Humans; Male; Animals; Mice; Asthenozoospermia; Palmitic Acid; Spermatogenesis; Testis; Infertility, Male; Polysaccharides
PubMed: 37484950
DOI: 10.3389/fendo.2023.1222635 -
Frontiers in Endocrinology 2023Asthenoteratozoospermia is one of the most common causes of male infertility. Several genes have been identified as genetic causative factors, but there is a...
INTRODUCTION
Asthenoteratozoospermia is one of the most common causes of male infertility. Several genes have been identified as genetic causative factors, but there is a considerable genetic heterogeneity underlying asthenoteratozoospermia. In this study, we performed a genetic analysis of two brothers from a consanguineous Uighur family in China to identify gene mutations causative for asthenoteratozoospermia-related male infertility.
METHODS
Two related patients with asthenoteratozoospermia from a large consanguineous family were sequenced by whole-exome sequencing and Sanger sequencing to identify disease-causing genes. Scanning and transmission electron microscopy analysis revealed ultrastructural abnormalities of spermatozoa. Quantitative real-time PCR (qRT-PCR) analysis and immunofluorescence (IF) analysis were used to assess the expression of the mutant messenger RNA (mRNA) and protein.
RESULTS
A novel homozygous frameshift mutation (c.2823dupT, p.Val942Cysfs*21) in was identified in both affected individuals and was predicted to be pathogenic. Papanicolaou staining and electron microscopy revealed multiple morphological and ultrastructural abnormalities of affected spermatozoa. qRT-PCR and IF analysis showed abnormal expression of DNAH6 in affected sperm, probably due to premature termination code and decay of abnormal 3' untranslated region (UTR) region of mRNA. Furthermore, intracytoplasmic sperm injection could achieve successful fertilization in infertile men with mutations.
DISCUSSION
The novel frameshift mutation identified in DNAH6 may contribute to asthenoteratozoospermia. These findings expand the spectrum of genetic mutations and phenotypes associated with asthenoteratozoospermia and may be useful for genetic and reproductive counseling in male infertility.
Topics: Humans; Male; Asthenozoospermia; Frameshift Mutation; Infertility, Male; RNA, Messenger; Semen; Sperm Tail; Dyneins
PubMed: 37424858
DOI: 10.3389/fendo.2023.1122004 -
Medicine Jul 2023Asthenozoospermia (AZS) is the commonest cause of male-related infertility. The patients with AZS easily exhibit infertility, with their wives having spontaneous... (Observational Study)
Observational Study
Asthenozoospermia (AZS) is the commonest cause of male-related infertility. The patients with AZS easily exhibit infertility, with their wives having spontaneous miscarriages or seeking assisted reproductive treatment. Reciprocal chromosomal translocation (RCT) is an important chromosome structural abnormality and has been reported to affect sperm motility. Genetic counseling for male RCT patients with AZS is still a challenge. This study reported 4 RCT carriers, which were 46,XY,t(1;6) (p36.1;p21), 46,XY,t (6;10) (p21;q11.2), 46,XY,t (6;11) (p21;p15), and 46,XY,t (6;17) (p21;q21), respectively. The association between chromosome 6p21 translocation and AZS is discussed, considering 19 published cases as well. In 6 patients with available semen parameters and 4 patients in this study, all of them were diagnosed with AZS. The SLC26A8 gene and the DNAH8 gene located on chromosome 6p21 are closely related to AZS by gene search using OMIM. For the chromosome 6p21 breakpoint, 72 pathogenic genes were found through the DECIPHER search. Gene ontology analysis showed that these target genes have several molecular functions and are strongly involved in various biological processes. The proteins expressed by these genes are involved in multiple cellular components. These results suggest that the breakpoint of chromosome 6p21 in male RCT carriers is closely related to AZS. The breakpoint may disrupt the structure and function of related genes, resulting in reduced sperm motility. Karyotype analysis should be recommended for AZS patients. Chromosomes and breakpoints involved in RCT should be paid attention to in genetic counseling for patients.
Topics: Male; Humans; Asthenozoospermia; Translocation, Genetic; Infertility, Male; Chromosome Aberrations; Karyotype
PubMed: 37417617
DOI: 10.1097/MD.0000000000034318 -
The World Journal of Men's Health Jan 2024Male overweight and obesity could affect sperm quality and reproductive health. However, the impact of body mass index (BMI) on assisted reproductive technology (ART)...
PURPOSE
Male overweight and obesity could affect sperm quality and reproductive health. However, the impact of body mass index (BMI) on assisted reproductive technology (ART) outcomes in oligospermia and/or asthenospermia patients is yet lacking. This study aims to assess the impact of paternal BMI on ART and neonatal outcomes among oligozoospermia and/or asthenospermia patients undergoing fertilization (IVF)/intracytoplasmic sperm injection (ICSI).
MATERIALS AND METHODS
In this study, 2,075 couples undergoing their first fresh embryo transfer between January 2015 and June 2022 were recruited. Following the World Health Organization's (WHO's) categories, couples were stratified into three cohorts based on paternal BMI: normal weight (18.5-24.9 kg/m²), overweight (25.0-29.9 kg/m²), and obese (≥30.0 kg/m²). Modified Poisson regression models were used to assess the associations of paternal BMI with fertilization, embryonic development, and pregnancy outcomes. Logistic regression models were performed to investigate the associations of paternal BMI with pregnancy loss and neonatal outcomes. Furthermore, stratified analyses were performed based on fertilization methods, male infertility cause, and maternal BMI.
RESULTS
Higher paternal BMI is associated with a lower likelihood of achieving normal fertilized (p-trend=0.002), Day 3 transferable (p-trend=0.007), and high-quality embryos (p-trend=0.046) in IVF cycles, rather than in ICSI cycles. Paternal BMI of oligospermia or asthenospermia was negatively correlated with day 3 transferable (p-trend=0.013 and 0.030) and high-quality embryos (p-trend=0.024 and 0.027). Moreover, for neonatal outcomes, paternal BMI was positively associated with macrosomia (p-trend=0.019), large for gestational age (LGA) (p-trend=0.031), and very LGA (p-trend=0.045).
CONCLUSIONS
Our data suggested that higher paternal BMI was associated with fetal overgrowth, reduced fertilization, and embryonic development potential. Among males with oligospermia and/or asthenospermia, the impact of overweight and obesity on the choice of fertilization method and the long-term effects on their offspring need to be further investigated.
PubMed: 37382283
DOI: 10.5534/wjmh.220286 -
Journal of Clinical Medicine Jun 2023(1) Background: While females start their gynecological examinations during puberty, only few men decide to be visited by urologists in their youth. Given the...
(1) Background: While females start their gynecological examinations during puberty, only few men decide to be visited by urologists in their youth. Given the participation in the EcoFoodFertility research project, our department had the opportunity to screen young males that were supposedly healthy. (2) Results: from January 2019 to July 2020, we evaluated 157 patients with sperm, blood analysis, and uroandrological examinations. The inclusion criteria were age 18-40 and absence of previous urological disease (urology-naïve). The primary endpoint of the study was to record uroandrological diseases that are occasionally discovered during examination in asymptomatic young men. The average age was 26.9 years (range 18-40); average testicular volume was 15.7 mL (range 12-22 mL); and 45.2% reported abnormal semen analysis: 62 cases of teratozoospermia, 27 asthenozoospermia, 18 oligozoospermia, and 2 azoospermia were discovered respectively; 4/157 patients were diagnosed with hypogonadism; 2 cases with suspicious testicular mass resulted in testicular cancer; and 31 suspected varicoceles and 8 patients with mild sexual dysfunctions were managed. (3) Conclusions: an uroandrological evaluation of young asymptomatic males allowed for the prompt diagnosis of different urological conditions, including cancerous ones, in our series. Despite being debatable, combining urological counselling with physical examination, semen analysis, and a laboratory profile could be useful and cost-effective in order to ameliorate male health.
PubMed: 37298000
DOI: 10.3390/jcm12113803 -
Cell Jun 2023Sperm motility is crucial for successful fertilization. Highly decorated doublet microtubules (DMTs) form the sperm tail skeleton, which propels the movement of...
Sperm motility is crucial for successful fertilization. Highly decorated doublet microtubules (DMTs) form the sperm tail skeleton, which propels the movement of spermatozoa. Using cryo-electron microscopy (cryo-EM) and artificial intelligence (AI)-based modeling, we determined the structures of mouse and human sperm DMTs and built an atomic model of the 48-nm repeat of the mouse sperm DMT. Our analysis revealed 47 DMT-associated proteins, including 45 microtubule inner proteins (MIPs). We identified 10 sperm-specific MIPs, including seven classes of Tektin5 in the lumen of the A tubule and FAM166 family members that bind the intra-tubulin interfaces. Interestingly, the human sperm DMT lacks some MIPs compared with the mouse sperm DMT. We also discovered variants in 10 distinct MIPs associated with a subtype of asthenozoospermia characterized by impaired sperm motility without evident morphological abnormalities. Our study highlights the conservation and tissue/species specificity of DMTs and expands the genetic spectrum of male infertility.
Topics: Male; Humans; Cryoelectron Microscopy; Artificial Intelligence; Sperm Motility; Semen; Spermatozoa; Microtubules; Sperm Tail; Microtubule Proteins; Infertility, Male
PubMed: 37295417
DOI: 10.1016/j.cell.2023.05.009 -
Asian Journal of Andrology Nov 2023
Topics: Male; Humans; Avena; Infertility, Male; Oligospermia; Asthenozoospermia; Spermatozoa
PubMed: 37282384
DOI: 10.4103/aja202322 -
The Journal of Biological Chemistry Jul 2023Asthenozoospermia characterized by decreased sperm motility is a major cause of male infertility, but the majority of the etiology remains unknown. Here, we showed that...
Asthenozoospermia characterized by decreased sperm motility is a major cause of male infertility, but the majority of the etiology remains unknown. Here, we showed that the cilia and flagella associated protein 52 (Cfap52) gene was predominantly expressed in testis and its deletion in a Cfap52 knockout mouse model resulted in decreased sperm motility and male infertility. Cfap52 knockout also led to the disorganization of the midpiece-principal piece junction of the sperm tail but had no effect on the axoneme ultrastructure in spermatozoa. Furthermore, we found that CFAP52 interacted with the cilia and flagella associated protein 45 (CFAP45) and knockout of Cfap52 decreased the expression level of CFAP45 in sperm flagellum, which further disrupted the microtubule sliding produced by dynein ATPase. Together, our studies demonstrate that CFAP52 plays an essential role in sperm motility by interacting with CFAP45 in sperm flagellum, providing insights into the potential pathogenesis of the infertility of the human CFAP52 mutations.
Topics: Animals; Humans; Male; Mice; Cilia; Flagella; Infertility, Male; Mice, Knockout; Proteins; Semen; Sperm Motility; Sperm Tail; Spermatozoa
PubMed: 37236356
DOI: 10.1016/j.jbc.2023.104858 -
Cellular and Molecular Life Sciences :... May 2023The sperm flagellum is a specialized type of motile cilium composed of a typical "9 + 2" axonemal structure with peri-axonemal structures, such as outer dense fibers...
The sperm flagellum is a specialized type of motile cilium composed of a typical "9 + 2" axonemal structure with peri-axonemal structures, such as outer dense fibers (ODFs). This flagellar arrangement is crucial for sperm movement and fertilization. However, the association of axonemal integrity with ODFs remains poorly understood. Here, we demonstrate that mouse BBOF1 could interact with both MNS1, an axonemal component, and ODF2, an ODF protein, and is required for sperm flagellar axoneme maintenance and male fertility. BBOF1 is expressed exclusively in male germ cells from the pachytene stage onwards and is detected in sperm axoneme fraction. Spermatozoa derived from Bbof1-knockout mice exhibit a normal morphology, however, reduced motility due to the absence of certain microtubule doublets, resulting in the failure to fertilize mature oocytes. Furthermore, BBOF1 is found to interact with ODF2 and MNS1 and is also required for their stability. Our findings in mice suggest that Bbof1 could also be essential for human sperm motility and male fertility, thus is a novel potential candidate gene for asthenozoospermia diagnosis.
Topics: Animals; Male; Mice; Axoneme; Fertility; Heat-Shock Proteins; Infertility, Male; Mice, Knockout; Semen; Sperm Motility; Spermatozoa
PubMed: 37198331
DOI: 10.1007/s00018-023-04800-0