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International Journal of Molecular... Nov 2023Pathogenic variants cause cystic fibrosis (CF), and CF-related disorders (CF-RD), including bilateral aplasia of the vas deferens (CBAVD). The spectrum of clinical...
Pathogenic variants cause cystic fibrosis (CF), and CF-related disorders (CF-RD), including bilateral aplasia of the vas deferens (CBAVD). The spectrum of clinical manifestations depends on the genotype. The frequency and spectrum of the variants vary between populations and clinical groups. variants and genotypes were analyzed in Russian men with CF ( = 546) and CBAVD syndrome ( = 125). Pathogenic variants were detected in 93.95% and 39.2% of the CF and CBAVD alleles, respectively. The most frequent c.1521_1523del (F508del; p.Phe508del) variant was found in 541 (49.5%) CF alleles. A total of 162 genotypes were revealed in CF patients, including 152 homozygous and 394 compound-heterozygous. The most common CF-genotype was F508del/F508del (24.9%). Other frequent CF-genotypes were F508del/3849+10kbC>T, F508del/CFTRdele2,3, and F508del/E92K. CF-causing variants and/or 5T allele were found in 88% of CBAVD patients: 5T/CFTRmut (48.0%), CFTRmut/N (17.6%), CFTRmut/CFTRmut (6.4%), 5T/5T (10.4%), 5T/N (5.6%) and N/N (12.0%), with the most common CBAVD-genotype being F508del/5T (29.6%). The allele frequencies of F508del, CFTRdele2,3 394delTT, and 3849+10kbC>T were significantly higher in CF patients. L138ins/L138ins, 2184insA/E92K, and L138ins/N genotypes were found in CBAVD, but not in CF patients. The results indicate certain differences in the frequency of some variants and genotypes in Russian CF and CBAVD patients.
Topics: Male; Humans; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Vas Deferens; Mutation; Genotype; Russia
PubMed: 38003474
DOI: 10.3390/ijms242216287 -
Urology Case Reports Nov 2023We report an exceedingly rare case of Klippel-Feil syndrome (KFS), compounded by ipsilateral absence of the vas deferens, renal agenesis, and diaphragmatic hernia....
We report an exceedingly rare case of Klippel-Feil syndrome (KFS), compounded by ipsilateral absence of the vas deferens, renal agenesis, and diaphragmatic hernia. Unilateral absence of the vas deferens was found incidentally during orchidopexy. To the best of our knowledge, no case of unilateral absence of the kidney and vas deferens has been reported in children with KFS.
PubMed: 37965125
DOI: 10.1016/j.eucr.2023.102600 -
Basic and Clinical Andrology Nov 2023Since the release of the combined oral contraceptive pill in 1960, women have shouldered the burden of contraception and family planning. Over 60 years later, this is... (Review)
Review
BACKGROUND
Since the release of the combined oral contraceptive pill in 1960, women have shouldered the burden of contraception and family planning. Over 60 years later, this is still the case as the only practical, effective contraceptive options available to men are condoms and vasectomy. However, there are now a variety of promising hormonal and non-hormonal male contraceptive options being studied. The purpose of this narrative review is to provide clinicians and laypeople with focused, up-to-date descriptions of novel strategies and targets for male contraception. We include a cautiously optimistic discussion of benefits and potential drawbacks, highlighting several methods in preclinical and clinical stages of development.
RESULTS
As of June 2023, two hormonal male contraceptive methods are undergoing phase II clinical trials for safety and efficacy. A large-scale, international phase IIb trial investigating efficacy of transdermal segesterone acetate (Nestorone) plus testosterone gel has enrolled over 460 couples with completion estimated for late 2024. A second hormonal method, dimethandrolone undecanoate, is in two clinical trials focusing on safety, pharmacodynamics, suppression of spermatogenesis and hormones; the first of these two is estimated for completion in December 2024. There are also several non-hormonal methods with strong potential in preclinical stages of development.
CONCLUSIONS
There exist several hurdles to novel male contraception. Therapeutic development takes decades of time, meticulous work, and financial investment, but with so many strong candidates it is our hope that there will soon be several safe, effective, and reversible contraceptive options available to male patients.
PubMed: 37940863
DOI: 10.1186/s12610-023-00204-z -
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 -
Acta Cirurgica Brasileira 2023To evaluate the viability of the porcine vas deferens as a realistic microsurgical training model for vasectomy reversal.
PURPOSE
To evaluate the viability of the porcine vas deferens as a realistic microsurgical training model for vasectomy reversal.
METHODS
The model uses swine testicles (vas deferent), which are usually discarded in large street markets since they are not part of Brazilian cuisine. The spermatic cord was carefully dissected, and the vas deferens were isolated, measuring 10 cm in length. A paper quadrilateral with 5 cm2 was built to delimit the surgical training field. The objective of the model is to simulate only the microsurgical step when the vas deferens are already isolated. The parameters analyzed were: feasibility for reproducing the technique, patency before and after performing the vasovasostomy, cost of the model, ease of acquisition, ease of handling, execution time, and model reproducibility.
RESULTS
The simulator presented low cost. All models made were viable with a texture similar to human, with positive patency obtained in 100% of the procedures. The internal and external diameters of the vas deferens varied between 0.2-0.4 mm and 2-3 mm, respectively, with a mean length of 9 ± 1.2 cm. The total procedure time was 43.28 ± 3.22 minutes.
CONCLUSIONS
The realistic model presented proved to be viable for carrying out vasectomy reversal training, due to its low cost, easy acquisition, and easy handling, and providing similar tissue characteristics to humans.
Topics: Humans; Male; Animals; Swine; Vasovasostomy; Reproducibility of Results; Testis; Spermatic Cord; Brazil
PubMed: 37646762
DOI: 10.1590/acb383023 -
BMC Zoology Aug 2023Chrysopa pallens is one of the most beneficial and effective natural predators, and is famous for its extensive distribution, wide prey spectrum, and excellent...
BACKGROUND
Chrysopa pallens is one of the most beneficial and effective natural predators, and is famous for its extensive distribution, wide prey spectrum, and excellent reproductive performance. This study examined the anatomy and fine structure of the C. pallens reproductive system and spermatogenesis.
RESULTS
The male reproductive system of C. pallens comprises a pair of testes, a vas deferens, seminal vesicles, accessory glands, and short ejaculatory ducts. The testes were already mature on the day of emergence, but the accessory glands did not mature until 5 days post-emergence. In early spermatids, the flagellum had an axoneme on one side of the two mitochondrial derivatives. The nucleus was surrounded by parallel crystalline and paracrystalline materials. The spermatid envelope extends towards the paracrystalline material in a tail-shaped wing. In mature spermatids, the axoneme is located between the two accessory bodies and mitochondrial derivative sets. The parallel-crystalline and paracrystalline materials disappeared. In the testes, the wall of seminal cysts consists of a layer of epithelium, a muscular-connective sheath, and several vesicles of different sizes. The mature seminal cysts contained 128 spermatozoa. The accessory gland is composed of six parts: ventral papilla-like protuberance, anterior glandular lobe, lateral glandular lobe, seminal cyst, posterior kidney-shaped lobe, and posterior papilla-like protuberance. Muscle fibers and secretory granules are extensive.
CONCLUSIONS
This study provides information on the reproductive system of C. pallens and offers a resource for taxonomy and reproductive biology.
PubMed: 37641154
DOI: 10.1186/s40850-023-00175-8 -
Heliyon Aug 2023To make early predictions of PACU VAS before surgery, we created a novel nomogram for the early prediction of PACU VAS in patients having laparoscopic radical excision...
INTRODUCTION
To make early predictions of PACU VAS before surgery, we created a novel nomogram for the early prediction of PACU VAS in patients having laparoscopic radical excision of colorectal cancer with fentanyl.
METHODS
From July 2018 to December 2020, a total of 101 patients in Zhongshan Hospital Affiliated to Fudan University who underwent laparoscopic radical resection of colorectal cancer were enrolled in this study. For feature selection, a stepwise regression model was utilized. Multivariable logistic regression analysis was used to establish a prediction model. We incorporated age, gender, weight, height, fentanyl dosage during operation, operation time, and genotype, and this was presented with a nomogram. The nomogram's performance was evaluated in terms of discrimination and clinical utility.
RESULTS
The signature, which comprised of seven carefully chosen characteristics, was linked to the PACU VAS for the development dataset. Predictors contained in the individualized prediction nomogram included age, gender, weight, height, fentanyl dosage during operation, operation time, and genotype. With an area under the ROC curve of 0.877 (95% CI, 0.6874-1.0000), the model showed good discrimination. The nomogram still had good discrimination. Decision curve analysis demonstrated that the nomogram was clinically useful.
CONCLUSIONS
The nomogram presented in this study incorporates age, gender, weight, height, fentanyl dosage during operation, operation time, and genotype and can be conveniently used to facilitate the individualized prediction of PACU VAS in patients undergoing laparoscopic radical resection of colorectal cancer with fentanyl.
PubMed: 37554790
DOI: 10.1016/j.heliyon.2023.e18560 -
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 -
Molecular Genetics & Genomic Medicine Nov 2023Isolated congenital bilateral absence of vas deferens (iCBAVD) in men results in obstructive azoospermia and is mainly caused by pathogenic variants in cystic fibrosis...
Compound heterozygous variants in CFTR with potentially reducing ATP-binding ability identified in Chinese infertile brothers with isolated congenital bilateral absence of vas deferens.
BACKGROUND
Isolated congenital bilateral absence of vas deferens (iCBAVD) in men results in obstructive azoospermia and is mainly caused by pathogenic variants in cystic fibrosis transmembrane conductance regulator (CFTR) or adhesion G protein-coupled receptor G2 (ADGRG2).
METHODS
The next-generation sequencing (NGS) was used to screen the mutations in the proband, and Sanger sequencings were performed to validate the compound heterozygous variant of CFTR in his family members. Protein structure simulation was performed to discover the potential pathological mechanism.
RESULTS
This study reported novel compound heterozygous CFTR mutations (NM:000492.4, Intron: 5T; c.3965_3969dupTTGGG: p.R1325Gfs*5) in two brothers with obstructive azoospermia. The compound heterozygous CFTR mutations were first screened out by NGS in an infertile male patient who exhibited iCBAVD from a nonconsanguineous Chinese family. Histological analysis of the testicular biopsy from this patient revealed normal spermatogenesis and mature spermatozoa were observed in the seminiferous tubules. Surprisingly, the same compound heterozygous CFTR mutations were also observed in his brothers who also exhibited iCBAVD, with their parents being a heterozygous carrier for the mutations, as verified by Sanger sequencing. Protein structure simulation revealed that these mutations potentially led to impaired ATP-binding ability of CFTR.
CONCLUSION
We identified novel compound heterozygous CFTR mutations in two brothers and summarized the literature regarding CFTR mutation and male infertility. Our study may contribute to the genetic diagnosis of iCBAVD and future genetic counseling.
Topics: Humans; Male; Azoospermia; Siblings; Cystic Fibrosis Transmembrane Conductance Regulator; East Asian People; Adenosine Triphosphate
PubMed: 37489040
DOI: 10.1002/mgg3.2249