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Frontiers in Endocrinology 2024Multiple morphological abnormalities of the sperm flagella (MMAF) is characterized by abnormal flagellar phenotypes, which is a particular kind of...
OBJECTIVE
Multiple morphological abnormalities of the sperm flagella (MMAF) is characterized by abnormal flagellar phenotypes, which is a particular kind of asthenoteratozoospermia. Previous studies have reported a comparable intracytoplasmic sperm injection (ICSI) outcome in terms of fertilization rate and clinical pregnancy rate in patients with MMAF compared with those with no MMAF; however, others have conflicting opinions. Assisted reproductive technology (ART) outcomes in individuals with MMAF are still controversial and open to debate.
METHODS
A total of 38 patients with MMAF treated at an academic reproductive center between January 2014 and July 2022 were evaluated in the current retrospective cohort study and followed up until January 2023. Propensity score matching was used to adjust for the baseline clinical characteristics of the patients and to create a comparable control group. The genetic pathogenesis of MMAF was confirmed by whole exome sequencing. The main outcomes were the embryo developmental potential, the cumulative pregnancy rate (CLPR), and the cumulative live birth rate (CLBR).
RESULTS
Pathogenic variants in known genes of , , , , and were identified in patients with MMAF. Laboratory outcomes, including the fertilization rate, 2PN cleavage rate, blastocyst formation rate, and available blastocyst rate, followed a trend of decline in the MMAF group ( < 0.05). Moreover, according to the embryo transfer times and complete cycles, the CLPR in the cohort of MMAF was lower compared with the oligoasthenospermia pool ( = 0.033 and = 0.020, respectively), while no statistical differences were observed in the neonatal outcomes.
CONCLUSION
The current study presented decreased embryo developmental potential and compromised clinical outcomes in the MMAF cohort. These findings may provide clinicians with evidence to support genetic counseling and clinical guidance in specific patients with MMAF.
Topics: Humans; Male; Female; Pregnancy; Pregnancy Rate; Adult; Retrospective Studies; Sperm Injections, Intracytoplasmic; Sperm Tail; Embryonic Development; Asthenozoospermia; Infertility, Male; Spermatozoa
PubMed: 38745955
DOI: 10.3389/fendo.2024.1377780 -
Journal of Medical Case Reports May 2024Bacterial infection of embryo culture medium is rare but may be detrimental. The main source of embryo culture contamination is semen. Assisted reproduction centers...
BACKGROUND
Bacterial infection of embryo culture medium is rare but may be detrimental. The main source of embryo culture contamination is semen. Assisted reproduction centers currently lack consensus regarding the methods for preventing and managing embryo culture infection. In our recent case, a successful pregnancy was achieved with intracytoplasmic sperm injection after failed conventional in vitro fertilization owing to bacterial contamination.
CASE PRESENTATION
We present a case report of two consecutive in vitro fertilization-intracytoplasmic sperm injection cycles with photo and video documentation of the bacterial growth. A 36-year-old Hungarian woman and her 37-year-old Hungarian partner came to our department. They had two normal births followed by 2 years of infertility. The major causes of infertility were a closed fallopian tube and asthenozoospermia. Bacterial infection of the embryo culture medium was observed during in vitro fertilization and all oocytes degenerated. The source was found to be the semen. To prevent contamination, intracytoplasmic sperm injection was used for fertilization in the subsequent cycle. Intracytoplasmic bacterial proliferation was observed in one of the three fertilized eggs, but two good-quality embryos were successfully obtained. The transfer of one embryo resulted in a successful pregnancy and a healthy newborn was delivered.
CONCLUSION
Intracytoplasmic sperm injection may be offered to couples who fail conventional in vitro fertilization treatment owing to bacteriospermia, as it seems to prevent infection of the embryo culture. Even if bacterial contamination appears, our case encourages us to continue treatment. Nevertheless, the development of new management guidelines for the prevention and management of bacterial contamination is essential.
Topics: Humans; Sperm Injections, Intracytoplasmic; Female; Pregnancy; Adult; Fertilization in Vitro; Male; Embryo Culture Techniques; Pregnancy Outcome; Embryo Transfer; Semen
PubMed: 38745332
DOI: 10.1186/s13256-024-04521-3 -
Phytomedicine : International Journal... Jul 2024Oligoasthenozoospermia is the most common type of semen abnormality in male infertile patients. Betaine (BET) has been proved to have pharmacological effects on...
BACKGROUND
Oligoasthenozoospermia is the most common type of semen abnormality in male infertile patients. Betaine (BET) has been proved to have pharmacological effects on improving semen quality. BET also belongs to endogenous physiological active substances in the testis. However, the physiological function of BET in rat testis and its pharmacological mechanism against oligoasthenozoospermia remain unclear.
PURPOSE
This research aims to prove the therapeutic effect and potential mechanism of BET on oligoasthenozoospermia rat model induced by Tripterygium wilfordii glycosides (TWGs).
METHODS
The oligoasthenozoospermia rat model was established by a continuous gavage of TWGs (60 mg/kg) for 28 days. Negative control group, oligoasthenozoospermia group, positive drug group (levocarnitine, 300 mg/kg), and 200 mg/kg, 400 mg/kg, and 800 mg/kg BET groups were created for exploring the therapeutic effect of BET on the oligoasthenozoospermia rat model. The therapeutic effect was evaluated by HE and TUNEL staining. Immunofluorescence assay of DNMT3A, PIWIL1, PRMT5, SETDB1, BHMT2, and METTL3, methylation capture sequencing, Pi-RNA sequencing, and molecular docking were used to elucidate potential pharmacological mechanisms.
RESULTS
It is proved that BET can significantly restore testicular pathological damage induced by TWGs, which also can significantly reverse the apoptosis of spermatogenic cells. The spermatogenic cell protein expression levels of DNMT3A, PIWIL1, PRMT5, SETDB1, BHMT2, and METTL3 significantly decreased in oligoasthenozoospermia group. 400 mg/kg and 800 mg/kg BET groups can significantly increase expression level of the above-mentioned proteins. Methylation capture sequencing showed that BET can significantly increase the 5mC methylation level of Spata, Spag, and Specc spermatogenesis-related genes. Pi-RNA sequencing proved that the above-mentioned genes produce a large number of Pi-RNA under BET intervention. Pi-RNA can form complexes with PIWI proteins to participate in DNA methylation of target genes. Molecular docking indicated that BET may not directly act as substrate for methyltransferase and instead participates in DNA methylation by promoting the methionine cycle and increasing S-adenosylmethionine synthesis.
CONCLUSION
BET has a significant therapeutic effect on oligoasthenozoospermia rat model induced by TWPs. The mechanism mainly involves that BET can increase the methylation level of Spata, Specc, and Spag target genes through the PIWI/Pi-RNA pathway and up-regulation of methyltransferases (including DNA methyltransferases and histone methyltransferases).
Topics: Male; Animals; Apoptosis; DNA Methylation; Betaine; Disease Models, Animal; Rats; Rats, Sprague-Dawley; Oligospermia; Tripterygium; Asthenozoospermia; Up-Regulation; Testis; Molecular Docking Simulation; Spermatogenesis; Methyltransferases; Spermatozoa
PubMed: 38735196
DOI: 10.1016/j.phymed.2024.155713 -
Cureus Apr 2024This case report revolves around a 37-year-old woman and her 39-year-old husband, who have been married for seven years and were seeking treatment for infertility. The...
This case report revolves around a 37-year-old woman and her 39-year-old husband, who have been married for seven years and were seeking treatment for infertility. The husband has been diagnosed with asthenozoospermia for the past six years and has been on continued medication, and the woman has been diagnosed with polycystic ovarian syndrome (PCOS). To improve fertility outcomes, this case report enlightens the treatment and medical strategy for people with PCOS. Treatment included low-dose ovarian stimulation for the removal of immature eggs, and then in vitro maturation (IVM) of those oocytes was done. Later, intracytoplasmic sperm injection (ICSI) was performed to form the blast. The formed blasts were later cryopreserved till embryo transfer. This case report highlights the importance of preventing the risk of ovarian hyperstimulation syndrome (OHSS) in patients with PCOS.
PubMed: 38707084
DOI: 10.7759/cureus.57486 -
American Journal of Men's Health 2024
Topics: Humans; Male; Acetylcysteine; Asthenozoospermia; Carnitine; Meta-Analysis as Topic; Acetylcarnitine; Treatment Outcome
PubMed: 38686842
DOI: 10.1177/15579883241249109 -
Biopreservation and Biobanking Apr 2024Many cellular processes in spermatozoa, including apoptosis and motility, are regulated by miRNA. Different miRNAs and molecular pathways are involved in...
Many cellular processes in spermatozoa, including apoptosis and motility, are regulated by miRNA. Different miRNAs and molecular pathways are involved in asthenozoospermia (AS) conditions, which are thought to be one of the causes of infertility with reduced sperm motility. Thirty-two semen samples from four Holstein bulls with normozoospermia (NS), total motility ≥ 70%, and progressive motility ≥ 60%, and 32 semen samples from four bulls with AS, total motility ≤ 40%, and progressive motility ≤ 32% were used to investigate the function of apoptosis-related miRNAs in the AS group. Samples were then aspirated into a 0.5 mL straw after dilution with a Tris-egg yolk extender and frozen at -196°C. After freezing, semen samples were thawed for 2 weeks at 37°C and sperm kinematic parameters, plasma membrane integrity, acrosome integrity, DNA fragmentation, apoptosis status, and expression of apoptosis-related miRNAs (miR-2114, miR-296-3p, miR-455-3p, and miR345-3p) were evaluated. Our results showed that the functional and flow cytometric parameters of the NS group were significantly better than those of the AS group. In the NS group, miR-455-3pp and miR-2412 were upregulated, while miR-345-3p was downregulated compared with the AS group. In the AS group, miR-296-39, miR-2412, and miR-345-3p levels were strongly correlated with membrane integrity, DNA fragmentation, and apoptosis status. The findings demonstrated that the selected miRNAs based on bioinformatic analysis in AS and NS samples had a substantial association with functional and flow cytometry indicators and may be involved in regulating apoptosis and motility in AS samples.
PubMed: 38686528
DOI: 10.1089/bio.2023.0135 -
Journal of Assisted Reproduction and... Apr 2024In a recent journal article, Chen et al. identified a germ cell-specific cofactor, STYXL1, associated with male fertility function. Deletion of STYXL1 prevents the LEGO...
In a recent journal article, Chen et al. identified a germ cell-specific cofactor, STYXL1, associated with male fertility function. Deletion of STYXL1 prevents the LEGO player CCT complex from properly folding key microtubule proteins of the sperm flagellum, which affects sperm motility and male fertility function.
PubMed: 38676841
DOI: 10.1007/s10815-024-03122-9 -
Human Reproduction Open 2024Is the mutation causative for male infertility?
STUDY QUESTION
Is the mutation causative for male infertility?
SUMMARY ANSWER
Our collected data underline the complex and devastating effect of the single-gene mutation on the testicular molecular network, leading to male reproductive failure.
WHAT IS KNOWN ALREADY
Recent data have revealed mutations in genes related to axonemal dynein arms as causative for morphology and motility abnormalities in spermatozoa of infertile males, including dysplasia of fibrous sheath (DFS) and multiple morphological abnormalities in the sperm flagella (MMAF). The nexin-dynein regulatory complex (N-DRC) coordinates the dynein arm activity and is built from the DRC1-DRC7 proteins. DRC5 (TCTE1), one of the N-DRC elements, has already been reported as a candidate for abnormal sperm flagella beating; however, only in a restricted manner with no clear explanation of respective observations.
STUDY DESIGN SIZE DURATION
Using the CRISPR/Cas9 genome editing technique, a mouse gene knockout line was created on the basis of the C57Bl/6J strain. The mouse reproductive potential, semen characteristics, testicular gene expression levels, sperm ATP, and testis apoptosis level measurements were then assessed, followed by visualization of N-DRC proteins in sperm, and protein modeling . Also, a pilot genomic sequencing study of samples from human infertile males (n = 248) was applied for screening of variants.
PARTICIPANTS/MATERIALS SETTING METHODS
To check the reproductive potential of KO mice, adult animals were crossed for delivery of three litters per caged pair, but for no longer than for 6 months, in various combinations of zygosity. All experiments were performed for wild-type (WT, control group), heterozygous and homozygous male mice. Gross anatomy was performed on testis and epididymis samples, followed by semen analysis. Sequencing of RNA (RNAseq; Illumina) was done for mice testis tissues. STRING interactions were checked for protein-protein interactions, based on changed expression levels of corresponding genes identified in the mouse testis RNAseq experiments. Immunofluorescence staining was performed to detect the N-DRC complex proteins: Tcte1 (Drc5), Drc7, Fbxl13 (Drc6), and Eps8l1 (Drc3) in mouse spermatozoa. To determine the amount of ATP in spermatozoa, the luminescence level was measured. In addition, immunofluorescence staining was performed to check the level of apoptosis via caspase 3 visualization on mouse testis samples. DNA from whole blood samples of infertile males (n = 137 with non-obstructive azoospermia or cryptozoospermia, n = 111 samples with a spectrum of oligoasthenoteratozoospermia, including n = 47 with asthenozoospermia) was extracted to perform genomic sequencing (WGS, WES, or Sanger). Protein prediction modeling of human-identified variants and the exon 3 structure deleted in the mouse knockout was also performed.
MAIN RESULTS AND THE ROLE OF CHANCE
No progeny at all was found for the homozygous males which were revealed to have oligoasthenoteratozoospermia, while heterozygous animals were fertile but manifested oligozoospermia, suggesting haploinsufficiency. RNA-sequencing of the testicular tissue showed the influence of mutations on the expression pattern of 21 genes responsible for mitochondrial ATP processing or linked with apoptosis or spermatogenesis. In males, the protein was revealed in only residual amounts in the sperm head nucleus and was not transported to the sperm flagella, as were other N-DRC components. Decreased ATP levels (2.4-fold lower) were found in the spermatozoa of homozygous mice, together with disturbed tail:midpiece ratios, leading to abnormal sperm tail beating. Casp3-positive signals (indicating apoptosis) were observed in spermatogonia only, at a similar level in all three mouse genotypes. Mutation screening of human infertile males revealed one novel and five ultra-rare heterogeneous variants (predicted as disease-causing) in 6.05% of the patients studied. Protein prediction modeling of identified variants revealed changes in the protein surface charge potential, leading to disruption in helix flexibility or its dynamics, thus suggesting disrupted interactions of TCTE1 with its binding partners located within the axoneme.
LARGE SCALE DATA
All data generated or analyzed during this study are included in this published article and its supplementary information files. RNAseq data are available in the GEO database (https://www.ncbi.nlm.nih.gov/geo/) under the accession number GSE207805. The results described in the publication are based on whole-genome or exome sequencing data which includes sensitive information in the form of patient-specific germline variants. Information regarding such variants must not be shared publicly following European Union legislation, therefore access to raw data that support the findings of this study are available from the corresponding author upon reasonable request.
LIMITATIONS REASONS FOR CAUTION
In the study, the fertilization performance of sperm from homozygous male mice was not checked.
WIDER IMPLICATIONS OF THE FINDINGS
This study contains novel and comprehensive data concerning the role of in male infertility. The gene is the next one that should be added to the 'male infertility list' because of its crucial role in spermatogenesis and proper sperm functioning.
STUDY FUNDING/COMPETING INTERESTS
This work was supported by National Science Centre in Poland, grants no.: 2015/17/B/NZ2/01157 and 2020/37/B/NZ5/00549 (to M.K.), 2017/26/D/NZ5/00789 (to A.M.), and HD096723, GM127569-03, NIH SAP #4100085736 PA DoH (to A.N.Y.). The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
PubMed: 38650655
DOI: 10.1093/hropen/hoae020 -
BMC Medical Genomics Apr 2024This report presents a clinical case of syndromic rod-cone dystrophy due to a splice site variant in the ARL2BP gene causing situs inversus, asthenozoospermia,...
A novel homozygous splice site variant in ARL2BP causes a syndromic autosomal recessive rod-cone dystrophy with situs inversus, asthenozoospermia, unilateral renal agenesis and microcysts.
BACKGROUND
This report presents a clinical case of syndromic rod-cone dystrophy due to a splice site variant in the ARL2BP gene causing situs inversus, asthenozoospermia, unilateral renal agenesis and microcysts. The presence of renal agenesis and cryptorchidism expands the clinical manifestations due to ARL2BP variants. The detailed, long-term follow-up contributes valuable insights into disease progression, aiding clinical diagnosis and patient management.
CASE PRESENTATION
The male patient complained of photophobia as the first symptom when he was 20 years old followed by nyctalopia, loss of central visual acuity and peripheral visual field ten years later. Genetic analysis identified a likely pathogenic homozygous variant (c.294-1G > C) involving the splicing acceptor site of intron 4. Reported symptoms together with full-field stimulus threshold testing, electroretinogram and advanced multimodal imaging allowed us to recognize the typical characteristics of a mixed retinal dystrophy. Despite the end-stage retinal disease, this patient still retained a useful residual vision at 63 years and had a slow disease progression during the last 5 years of evaluation.
DISCUSSION AND CONCLUSIONS
Our findings underscore the variable clinical presentation of ARL2BP variants, emphasizing the importance of a nuanced approach in diagnosing and managing patients. The presence of renal cysts warrants consideration of a differential diagnosis, particularly with Senior-Loken (SLS), Bardet-Biedl (BBS) and Joubert syndromes (JS) but also with Short Rib Thoracic Dysplasia 9, highlighting the need for careful phenotypic evaluation in these cases.
Topics: Humans; Male; Cone-Rod Dystrophies; Congenital Abnormalities; Homozygote; Kidney; Kidney Diseases; RNA Splice Sites; Situs Inversus; Syndrome; Middle Aged
PubMed: 38649918
DOI: 10.1186/s12920-024-01868-w -
Zhonghua Nan Ke Xue = National Journal... Oct 2023To study the correlation, consistency, and variations between two assays of DNA fragmentation index based on acridine orange (AO) staining via AI-based fluorescence...
[Comparative analysis of two assaysin detection of sperm DNA fragmentation index, flow cytometry and AI-based fluorescence microscopy, based on AO staining: A multicentre study].
OBJECTIVE
To study the correlation, consistency, and variations between two assays of DNA fragmentation index based on acridine orange (AO) staining via AI-based fluorescence microscopy(AI-DFI), and flow cytometry (FCM-DFI) across multiple centers.
METHODS
We selected 421 male patients from Nanjing Drum Tower hospital ( Hospital G) (226 cases), Eastern Theatre General Hospital (Hospital J) (89 cases) and Jiangsu Province Hospital (Hospital S) (106 cases) . Semen samples from each patient were analyzed for routine semen parameters and for DFI using both AI fluorescence microscopy and flow cytometry. We studied the two methods' stability as well as the correlation, consistency, and variation between the two methods' results in various centers.
RESULTS
The two replicate studies' results of AI-DFI and the three centers' FCM-DFI for linear regression analysis indicated strong stability (R2>0.9).Overall(Group A), the AI-DFI results demonstrated good correlation and consistency with the FCM-DFI results of three centers (r>0.85;ICC>0.9).The semen specimens were categorized into two groups: normal specimen group (group B) and abnormal specimen group (group C) (including asthenozoospermia, oligospermia, and semen samples with high impurities).Group C's results showed a decline in correlation and consistency when compared to group A and group B, whereas group B's results showed a little rise in correlation and consistency when compared to group A. Although the consistency and correlation between the results of the two DFI testing methods in the three centers were good, there was still a significant difference between Groups A and C (P<0.05), and in Group B there was a significant difference between the two DFI testing methods only in Hospital G (p=0.02), with no significant difference in Hospitals J and S (P> 0.05).
CONCLUSION
The two detection methods exhibit good stability and correlation. However, significant differences are observed in the DFI detection methods in samples with abnormal semen parameters and high complexity. The main reason for these significant differences may lie in the variations in detection principles. Each detection method has its own advantages, allowing clinical or research settings to choose between them based on laboratory conditions or specific requirements.
Topics: Humans; Male; Semen; Semen Analysis; Flow Cytometry; DNA Fragmentation; Spermatozoa; Microscopy, Fluorescence; Staining and Labeling; Artificial Intelligence; Infertility, Male
PubMed: 38639663
DOI: No ID Found