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Frontiers in Genetics 2022Congenital absence of the vas deferens (CAVD) is a major cause of obstructive azoospermia. Mutations of and cause the majority of CAVD. Despite this, 10%-20% of CAVD...
Congenital absence of the vas deferens (CAVD) is a major cause of obstructive azoospermia. Mutations of and cause the majority of CAVD. Despite this, 10%-20% of CAVD patients remain without a clear genetic diagnosis. Herein, the and genes were first sequenced using Sanger sequencing in 50 CAVD patients. Whole-exome sequencing (WES) was used to further identify potential novel genetic causes in CAVD with hypospadias. In total, 29 of 50 CAVD patients carried at least one mutation, but no mutation was found. 5T was found to be the most frequent variant in our CAVD populations. Seven CAVD patients with hypospadias were further analyzed using WES. No homozygous or compound heterozygous mutations related to disorders of sex development (DSDs) or male infertility were identified by WES. CAVD with hypospadias presented lower testicular volume (9.71 ± 2.14 ml vs. 14.45 ± 2.93 ml, < 0.001) and higher FSH level (FSH: 7.28 ± 3.91 IU/L vs. 4.24 ± 1.96 IU/L, = 0.027) than CAVD without hypospadias. It is worth noting that neither or mutation nor homozygous or compound heterozygous gene mutations were identified in seven CAVD cases with hypospadias. However, nine heterozygous or hemizygous mutations were selected as potential pathogenic genes in CAVD with hypospadias. In conclusion, variants, especially 5T, play a major role in the Chinese CAVD population CAVD with hypospadias shows relatively lower testicular spermatogenesis, suggesting a different genetic basis or pathogenic factor from cystic fibrosis/CAVD or unilateral renal agenesis/CAVD.
PubMed: 36437957
DOI: 10.3389/fgene.2022.1035468 -
ZooKeys 2022Two new earthworm species are described, namely and The former can be recognized by having male pores on spiniform penises in intersegment 10/11, an erect and...
Two new earthworm species are described, namely and The former can be recognized by having male pores on spiniform penises in intersegment 10/11, an erect and sac-shaped spermathecal atrium, glandular prostate, the capsule coiled one round, the vas deferens strongly coiled but small, two large, round, genital markings on segments ix-x, and three gizzards in xiii-xv. The latter species is distinguished in having the male pores placed on highly elevated, backwardly directed, conical penises in 10/11, a slender spermathecal atrium, a glandular prostate, a somewhat folded capsule, the vas deferens strongly coiled as a bunch and equal size to the testis sacs, a pair of genital markings located closely anterior to the penises with 1-3 additional ones in xi-xii, and three or four gizzards in xiii-xvi. The DNA barcode fragment of the COI gene was extracted for each species, and the COI genetic distances and phylogenetic analysis also supported two new species..
PubMed: 36761441
DOI: 10.3897/zookeys.1099.72112 -
Asian Journal of Andrology 2021Recent data suggest that cystic fibrosis transmembrane conductance regulator (CFTR) gene alterations negatively impact male fertility beyond obstruction. We sought to... (Comparative Study)
Comparative Study
Recent data suggest that cystic fibrosis transmembrane conductance regulator (CFTR) gene alterations negatively impact male fertility beyond obstruction. We sought to compare gene alterations, sperm retrieval rates, and intracytoplasmic sperm injection (ICSI) outcomes among men with cystic fibrosis (CF) disease and congenital bilateral absence of the vas deferens (CBAVD) only. We retrospectively evaluated all men who underwent surgical sperm retrieval at two academic, high-volume andrology centers from 2010 to 2018. Only men with documented CFTR alterations and obstructive azoospermia from either CBAVD or CF were included. Differences between groups for CFTR abnormality, sperm retrieval, and ICSI outcomes were statistically analyzed. Overall, 39 patients were included with 10 in the CF and 29 in the CBAVD groups. Surgical sperm retrieval rates were significantly lower in the CF group for sperm concentration (14.8 × 10 ml-1 vs 61.4 × 10 ml, P = 0.02) and total motile sperm count (2.9 million vs 11.4 million, P = 0.01). This difference was only predicted by homozygous delta F508 CFTR mutations (P < 0.05). The CF group also demonstrated a significantly higher rate of rescue testicular sperm extraction (70.0% vs 27.6%, P < 0.03) and lower fertilization rate with ICSI (32.5% vs 68.9%, P < 0.01). In conclusion, those with CF demonstrated lower sperm quality, greater difficulty with sperm retrieval, and worse ICSI outcomes compared with CBAVD-only patients. Homozygous delta F508 CFTR mutations appear to significantly impair spermatogenesis and sperm function.
Topics: Adult; Azoospermia; Cystic Fibrosis; Humans; Male; Male Urogenital Diseases; Sperm Injections, Intracytoplasmic; Sperm Retrieval; Treatment Outcome; Vas Deferens
PubMed: 32930103
DOI: 10.4103/aja.aja_48_20 -
Molecular Medicine Reports Nov 2020Congenital bilateral absence of the vas deferens (CBAVD) is predominantly caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.... (Review)
Review
Mutations of the cystic fibrosis transmembrane conductance regulator gene in males with congenital bilateral absence of the vas deferens: Reproductive implications and genetic counseling (Review).
Congenital bilateral absence of the vas deferens (CBAVD) is predominantly caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. CBAVD accounts for 2‑6% of male infertility cases and up to 25% of cases of obstructive azoospermia. With the use of pre‑implantation genetic diagnosis, testicular or epididymal sperm aspiration, intracytoplasmic sperm injection and in vitro fertilization, patients affected by CBAVD are able to have children who do not carry CFTR gene mutations, thereby preventing disease. Therefore, genetic counseling should be provided to couples receiving assisted reproductive techniques to discuss the impact of CFTR gene mutations on reproductive health. In the present article, the current literature concerning the CFTR gene and its association with CBAVD is reviewed.
Topics: Azoospermia; Cystic Fibrosis Transmembrane Conductance Regulator; Female; Genetic Counseling; Humans; Infertility, Male; Male; Male Urogenital Diseases; Mutation; Reproduction; Reproductive Techniques, Assisted; Vas Deferens
PubMed: 33000223
DOI: 10.3892/mmr.2020.11456 -
Journal of Healthcare Engineering 2021Inguinal hernia repair is one of the most frequently conducted surgical procedures worldwide. Laparoscopic inguinal hernia repair is considered to be technically...
Inguinal hernia repair is one of the most frequently conducted surgical procedures worldwide. Laparoscopic inguinal hernia repair is considered to be technically challenging. Artificial intelligence technology has made significant progress in medical imaging, but its application in laparoscopic surgery has not been widely carried out. Our aim is to detect vas deferens images in laparoscopic inguinal hernial repair using the convolutional neural network (CNN) and help surgeons to identify the vas deferens in time. We collected surgery videos from 35 patients with inguinal hernia who underwent laparoscopic hernia repair. We classified and labeled the images of the vas deferens and used the CNN to learn the image features. Totally, 2,600 images (26 patients) were labeled for training and validating the neural network and 1,200 images (6 patients) and 6 short video clips (3 patients) for testing. We adjusted the model parameters and tested the performance of the model under different confidence levels and IoU and used the chi-square to analyze the statistical difference in the video test dataset. We evaluated the model performance by calculating the true positive rate (TPR), true negative rate (TNR), accuracy (ACC), positive predictive value (PPV), and 1-score at different confidence levels of 0.1 to 0.9. In confidence level 0.4, the results were TPR 90.61%, TNR 98.67%, PPV 98.57%, ACC 94.61%, and 1 94.42%, respectively. The average precision (AP) was 92.38% at IoU 0.3. In the video test dataset, the average values of TPR and TNR were 90.11% and 95.76%, respectively, and there was no significant difference among the patients. The results suggest that the CNN can quickly and accurately identify and label vas deferens images in laparoscopic inguinal hernia repair.
Topics: Artificial Intelligence; Hernia, Inguinal; Humans; Laparoscopy; Male; Neural Networks, Computer; Vas Deferens
PubMed: 34603649
DOI: 10.1155/2021/5578089 -
Parasites & Vectors Jun 2021Canine leishmaniosis (CanL) is a zoonotic disease caused by Leishmania infantum. Although usually transmitted by phlebotomine sand flies, infection by vertical...
BACKGROUND
Canine leishmaniosis (CanL) is a zoonotic disease caused by Leishmania infantum. Although usually transmitted by phlebotomine sand flies, infection by vertical transmission and by blood transfusion have also been reported.
METHODS
We describe the very early onset of clinical leishmaniosis, starting from 2 months of age, in a litter of pups born to an infected dam and sire. Seven pups from the litter of nine living in different households showed alopecic, exfoliative dermatitis and ulcerative cutaneous lesions. All pups and both parents were tested on at least one occasion both serologically, by enzyme-linked immunosorbent assay (ELISA), and by polymerase chain reaction (PCR) targeting the Leishmania ribosomal operon internal transcribed spacer 1 region and a short fragment of the kinetoplast minicircle; positive amplicons were sequenced.
RESULTS
All nine pups were PCR positive for L. infantum verified by DNA sequencing, seven were positive by conjunctival, five by blood, four by lymph node, and one by skin PCR from an ulcerative lesion. Both pups with no clinical signs were seronegative, while five of the seven pups with dermatologic abnormalities were seropositive by ELISA. The sire had typical clinical dermatologic and visceral findings of CanL, was seropositive and PCR positive for L. infantum in the lymph node and fluid from the vas deferens tested after the testes were removed by castration. The dam was sub-clinically infected and seronegative, but positive by blood, lymph node and conjunctival PCR for L. infantum. Allopurinol administered to all clinically affected dogs resulted in clinical recovery.
CONCLUSIONS
Infection with L. infantum in both parents, the very early age of clinical onset among most of the pups, and the fact that the puppies were born and detected with signs of leishmaniosis in the winter, which is a season without sand fly activity in Israel, strongly suggest vertical transmission. Awareness of the possibility of vertical transmission of L. infantum and infection in littermates should be increased. It is recommended that littermates of young dogs with clinical leishmaniosis should be tested for sub-clinical infection as they may also be infectious to sand flies and thus to other dogs and to humans. Restricting the mating of infected bitches should also be considered to prevent the vertical transmission of the infection.
Topics: Animals; Dog Diseases; Dogs; Female; Fetal Diseases; Infectious Disease Transmission, Vertical; Israel; Leishmania infantum; Leishmaniasis, Visceral; Male; Skin; Uterus
PubMed: 34130703
DOI: 10.1186/s13071-021-04824-0 -
Biological Research Oct 2023In vitro incubation of epididymal and vas deferens sperm with Mn induces Sperm Chromatin Fragmentation (SCF), a mechanism that causes double-stranded breaks in...
BACKGROUND
In vitro incubation of epididymal and vas deferens sperm with Mn induces Sperm Chromatin Fragmentation (SCF), a mechanism that causes double-stranded breaks in toroid-linker regions (TLRs). Whether this mechanism, thought to require the participation of topoisomerases and/or DNAses and thus far only described in epididymal mouse sperm, can be triggered in ejaculated sperm is yet to be elucidated. The current study aimed to determine if exposure of pig ejaculated sperm to divalent ions (Mn and Mg) activates SCF, and whether this has any impact on sperm function and survival. For this purpose, sperm DNA integrity was evaluated through the Comet assay and Pulsed Field Gel Electrophoresis (PFGE); sperm motility and agglutination were assessed with computer assisted sperm analysis (CASA); and sperm viability and levels of total reactive oxygen species (ROS) and superoxides were determined through flow cytometry.
RESULTS
Incubation with Mn/Ca activated SCF in a dose-dependent (P < 0.05) albeit not time-dependent manner (P > 0.05); in contrast, Mg/Ca only triggered SCF at high concentrations (50 mM). The PFGE revealed that, when activated by Mn/Ca or Mg/Ca, SCF generated DNA fragments of 33-194 Kb, compatible with the size of one or multiple toroids. Besides, Mn/Ca affected sperm motility in a dose-dependent manner (P < 0.05), whereas Mg/Ca only impaired this variable at high concentrations (P < 0.05). While this effect on motility was concomitant with an increase of agglutination, neither viability nor ROS levels were affected by Mn/Ca or Mg/Ca treatments.
CONCLUSION
Mn/Ca and Mn/Ca were observed to induce SCF in ejaculated sperm, resulting in DNA cleavage at TLRs. The activation of this mechanism by an intracellular, non-oxidative factor sheds light on the events taking place during sperm cell death.
Topics: Male; Mice; Animals; Swine; Chromatin; Reactive Oxygen Species; Semen; Sperm Motility; Spermatozoa; DNA; DNA Fragmentation
PubMed: 37876007
DOI: 10.1186/s40659-023-00467-w -
Genes Jul 2023(1) Introduction: Pathogenic variants in the (Cystic Fibrosis Transmembrane conductance Regulator, OMIM: 602421) gene cause Cystic Fibrosis (CF, OMIM: 219700) and...
(1) Introduction: Pathogenic variants in the (Cystic Fibrosis Transmembrane conductance Regulator, OMIM: 602421) gene cause Cystic Fibrosis (CF, OMIM: 219700) and CF-related disorders (CF-RD), often accompanied by obstructive azoospermia due to congenital bilateral aplasia of vas deferens (CBAVD, OMIM: 277180) in male patients. The L138ins (c.413_415dup; p. (Leu138dup)) is a mild variant in the gene that is relatively common among CF-patients in Slavic populations. The frequency of this variant in Russian infertile men has not been sufficiently studied; (2) Materials and Methods: The sample consisted of 6033 Russian infertile men. The patients were tested for 22 common in Russian populations pathogenic variants of the gene and the IVS9Tn-polymorphic locus of the intron 9. Molecular-genetic studies were performed using amplified fragment length polymorphism (AFLP-PCR), multiplex ligation-dependent probe amplification (MLPA), and nested PCR (for analysis of the IVS9Tn-polymorphic locus); (3) Results: Pathogenic variants in the were detected in 3.9% of patients. The most frequent variants were F508del and CFTRdele2.3(21kb), accounted for 61.0% and 7.1% of detected variants, respectively. The L138ins variant was detected in 17 (0.28%) individuals: one of them was homozygous, 10 patients were heterozygous, and 6 patients were compound-heterozygous (F508del/L138ins, = 4; L138ins/N1303K, = 1; L138ins/5T, = 1). Two pathogenic CF-causing variants in the gene were detected in 8 patients, including 7 compound heterozygous (F508del/L138ins, = 4; F508del/N1303K, = 1; 2184insA/E92K, = 1; 3849+10kbC>T/E92K, = 1) and one homozygous (L138ins/L138ins). The L138ins variant was found in 7 out of 16 (43.75%) chromosomes in six of these patients. The most common pathogenic variant, F508del, was identified in five out of them, in 5 of 16 (31.25%) chromosomes. The allele frequency (AF) of the L138ins variant in the sample has been found to be 0.0014.; (4) Conclusions: The L138ins variant of the gene is the third most common variant after F508del and CFTRdele2.3(kb) among Russian infertile men.
Topics: Humans; Male; Amplified Fragment Length Polymorphism Analysis; Cystic Fibrosis Transmembrane Conductance Regulator; Gene Frequency; Mutation; Russia; Infertility, Male
PubMed: 37510311
DOI: 10.3390/genes14071407 -
BMC Urology Feb 2022The incidence of 47, XYY syndrome in live-born male infants is 1/1000. Due to its variable clinical symptoms, the diagnosis is easy to miss. The incidence of congenital... (Review)
Review
BACKGROUND
The incidence of 47, XYY syndrome in live-born male infants is 1/1000. Due to its variable clinical symptoms, the diagnosis is easy to miss. The incidence of congenital bilateral absence of the vas deferens (CBAVD) in infertile men is 1-2%. The main cause is the mutation of CFTR and ADGAG2 genes.
CASE PRESENTATION
The patient was a 33-year-old man who visited a doctor 5 years ago due to infertility. The investigation revealed that the patient's secondary sexual characteristics, testicular, and penis development were normal, and there was no gynecomastia, but the bilateral vas deferens and epididymis were not palpable. Transrectal ultrasound showed that the left seminal vesicle was missing, and the right seminal vesicle was atrophied. No abnormality was observed in Y chromosome microdeletion. Karyotype analysis indicated that the patient was 46, XY/47, XYY mosaic. Genetic testing found heterozygous mutations at two sites of CFTR (c263T > G and c2249C > T).
CONCLUSIONS
Herein, we report the rare case of a male patient with clinical manifestations of infertility, chromosome 46, XY/47, XXY mosaic type, simultaneously manifested as the absence of bilateral vas deferens. Two pathogenic heterozygous CFTR gene mutations were found. Given the low genetic risk of the disease, we recommend that patients undergo intracytoplasmic sperm injection (ICSI) for fertility assessment.
Topics: Adult; Cystic Fibrosis Transmembrane Conductance Regulator; Heterozygote; Humans; Infertility, Male; Karyotyping; Male; Mutation; Sex Chromosome Disorders; Sperm Injections, Intracytoplasmic; Ultrasonography; Vas Deferens; XYY Karyotype
PubMed: 35109852
DOI: 10.1186/s12894-022-00965-1 -
Autonomic Neuroscience : Basic &... Nov 2021Geoff Burnstock created an outstanding scientific legacy that includes identification of adenosine 5'-triphosphate (ATP) as an inhibitory neurotransmitter in the gut,...
Geoff Burnstock created an outstanding scientific legacy that includes identification of adenosine 5'-triphosphate (ATP) as an inhibitory neurotransmitter in the gut, the discovery and characterisation of a large family of purine and uridine nucleotide-sensitive ionotropic P2X and metabotropic P2Y receptors and the demonstration that ATP is as an excitatory cotransmitter in autonomic nerves. The evidence for cotransmission includes that: 1) ATP is costored with noradrenaline in synaptic vesicles in postganglionic sympathetic nerves innervating smooth muscle tissues, including the vas deferens and most arteries. 2) When coreleased with noradrenaline, ATP acts at postjunctional P2X1 receptors to elicit depolarisation, Ca influx, Ca sensitisation and contraction. 3) ATP is also coreleased with acetylcholine from postganglionic parasympathetic nerves innervating the urinary bladder, where it stimulates postjunctional P2X1 receptors, and a second, as yet unidentified site to evoke contraction of detrusor smooth muscle. In both systems membrane-bound ecto-enzymes and soluble nucleotidases released from postganglionic nerves dephosphorylate ATP and so terminate its neurotransmitter actions. Currently, the most promising potential area of therapeutic application relating to cotransmission is treatment of dysfunctional urinary bladder. This family of disorders is associated with the appearance of a purinergic component of neurogenic contractions. This component is an attractive target for drug development and targeting it may be a rewarding area of research.
Topics: Adenosine Triphosphate; Autonomic Pathways; Humans; Male; Muscle Contraction; Muscle, Smooth; Norepinephrine; Parasympathetic Nervous System; Urinary Bladder; Vas Deferens
PubMed: 34340045
DOI: 10.1016/j.autneu.2021.102860