Background: Our previous studies have demonstrated the cystic fibrosis transmembrane conductance regulator (CFTR) is important for capacitation and male fertility in mouse and guinea pig spermatozoa. However, the exact function of CFTR on human sperm fertilizing capacity, and correlation with sperm quality has not been established. The present study may shed light on some unexplained male infertility, and on a possible new method for diagnosis of male infertility and strategy for male contraception.
Methods: To assess the effect of CFTR on human sperm fertilizing capacity, we examined sperm capacitation and the acrosome reaction using chlortetracycline staining, analyzed sperm hyperactivation by computer-assisted semen analysis (CASA), measured intracellular cAMP levels using ElA and evaluated sperm penetration of zona-free hamster eggs assay in fertile men. The percentage of spermatozoa expressing CFTR from fertile, healthy and infertile men (mainly teratospermic, asthenoteratospermic, asthenospermic and oligospermic) was conducted by indirect immunofluorescence staining.
Results: Progesterone significantly facilitated human sperm capacitation and ZP3 triggered the acrosome reaction, both were significantly inhibited by CFTR inhibitor-172 (CFTRinh-172; 10 nM-1 microM) in a dose-dependent manner. The presence of 100 nM CFTRinh-172 markedly depressed intracellular cAMP levels, sperm hyperactivation and sperm penetration of zona-free hamster eggs. In addition, the percentage of spermatozoa expressing CFTR in the fertile men was significantly higher than healthy and infertile men categories (P < 0.01).
Conclusions: CFTR is essential for human sperm fertilizing capacity and the impairment of CFTR expression in spermatozoa is correlated with a reduction of sperm quality. These results suggest that defective expression of CFTR in human sperm may lead to the reduction of sperm fertilizing capacity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/humrep/dep406 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Novel variants of FSIP2 and SPEF2 cause varying degrees of spermatozoa damage in MMAF patients and favorable ART outcomes.
J Assist Reprod Genet
January 2025
NHC Key Laboratory of Human Stem Cell and Reproductive Engineering, School of Basic Medical Sciences, Central South University, Changsha, China.
Purpose: This study identified novel variants of the FSIP2 and SPEF2 genes in multiple morphological abnormalities of the sperm flagella (MMAF) patients and to investigate the potential effect of variations on male infertility and assisted reproductive outcomes.
Methods: Whole-exome sequencing was performed in 106 Chinese MMAF patients. The discovered variants were evaluated in silico and confirmed by Sanger sequencing.
Role of GPR55 receptor in bovine sperm capacitation.
Andrology
January 2025
Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Facultad de Medicina-Universidad de Buenos Aires (UBA/CONICET), Buenos Aires, Argentina.
Background: Endocannabinoids like anandamide (AEA), among other lipids, are recognized signaling molecules that participate in reproductive events.
Objectives: Our aims were to characterize orphan G protein-coupled receptor (GPR55) presence; investigate GPR55 activation by AEA and determine GPR55 role in the bovine sperm function.
Materials And Methods: GPR55 presence was assessed by immunocytochemistry.
A non-hormonal reversible contraceptive targeting GSK3α, a protein kinase, essential for epididymal sperm maturation.
Andrology
January 2025
Manipal Centre for Biotherapeutics Research, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Background And Objectives: Epididymal transit renders key competence to mammalian spermatozoa for fertilizing eggs. Generally, the two paralogs of glycogen synthase kinase 3, GSK3α and GSK3β, functionally overlap except in testis and sperm. We showed that GSK3α is essential for epididymal sperm maturation and fertilization.
View Article and Find Full Text PDFHuman asthenozoospermia: Update on genetic causes, patient management, and clinical strategies.
Andrology
January 2025
Institute for Advanced Biosciences, INSERM U 1209, CNRS UMR 5309, Université Grenoble Alpes, Team "Physiopathology and Pathophysiology of Sperm Cells", Grenoble, France.
Background: In mammals, sperm fertilization potential relies on efficient progression within the female genital tract to reach and fertilize the oocyte. This fundamental property is supported by the flagellum, an evolutionarily conserved organelle, which contains dynein motor proteins that provide the mechanical force for sperm propulsion and motility. Primary motility of the sperm cells is acquired during their transit through the epididymis and hyperactivated motility is acquired throughout the journey in the female genital tract by a process called capacitation.
View Article and Find Full Text PDF"Pregnancy in a non-communicating rudimentary uterine horn managed with laparoscopy in the first trimester".
J Minim Invasive Gynecol
December 2024
Indigo womens centre, Chennai, India. Electronic address:
A 23-year-old woman, conceived by ovulation induction presented at 10 weeks amenorrhea with abdominal pain and a positive urinary Beta HCG. 2D ultrasound suggested a right-sided ectopic pregnancy. On 3D ultrasound imaging, an unicornuate uterus with a right rudimentary horn pregnancy of size 6 cm was diagnosed [Figure 1].
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!