Related Experiment Video
Updated: Feb 4, 2026
09:30
Phosphopeptide Analysis of Rodent Epididymal Spermatozoa
Published on: December 30, 2014
13.5K
Biallelic mutations in PMFBP1 cause acephalic spermatozoa.
Yan-Wei Sha1, Xiong Wang2, Xiaohui Xu3
1Department of Reproductive Medicine, Xiamen Maternity and Child Care Hospital, Xiamen, China.
Clinical Genetics
|October 10, 2018
Summary
Mutations in the PMFBP1 gene cause acephalic spermatozoa, a condition leading to male infertility. This study identifies PMFBP1 as crucial for sperm head-flagella formation in humans and mice.
Area of Science:
- Genetics
- Reproductive Biology
- Molecular Biology
Background:
- Male infertility affects a significant portion of the population, with many cases of defective spermatogenesis remaining undiagnosed.
- Acephalic spermatozoa syndrome is a specific cause of primary infertility, but its genetic underpinnings are often unknown.
Purpose of the Study:
- To identify the genetic cause of acephalic spermatozoa in individuals with unexplained infertility.
- To elucidate the function of the PMFBP1 gene in sperm development and morphology.
Main Methods:
- Whole-exome sequencing was performed on two unrelated individuals with acephalic spermatozoa.
- PMFBP1 expression and localization were analyzed in human and mouse testes and sperm.
- Pmfbp1 knockout (KO) mouse models were generated to study the in vivo effects of gene absence.
- Label-free quantitative proteomic analysis and gene ontology analysis were conducted on sperm from KO and control mice.
Main Results:
- Homozygous and compound heterozygous truncating mutations in PMFBP1 were identified in patients with acephalic spermatozoa.
- PMFBP1 is highly and specifically expressed in the testis and localized to the head-flagella junction in sperm.
- Pmfbp1 KO mice exhibited the acephalic sperm phenotype, confirming PMFBP1's role.
- Proteomic analysis revealed significant alterations in protein expression in Pmfbp1 KO mice, particularly affecting Golgi vesicle transport, suggesting defects in head-neck junction formation.
Conclusions:
- Biallelic truncating mutations in PMFBP1 are a cause of acephalic spermatozoa syndrome in humans.
- PMFBP1 is essential for normal sperm morphology and the formation of the head-neck junction in both humans and mice.
- Defects in PMFBP1 function disrupt Golgi vesicle transport, impacting sperm head-flagella development.
More Related Videos
Related Concept Videos
01:39Mutations
94.5K
Overview
94.5K
01:35Mutations
44.5K
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
44.5K
00:36Viral Mutations
39.9K
A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
39.9K
01:09Mutation, Gene Flow, and Genetic Drift
64.3K
In a population that is not at Hardy-Weinberg equilibrium, the frequency of alleles changes over time. Therefore, any deviations from the five conditions of Hardy-Weinberg equilibrium can alter the genetic variation of a given population. Conditions that change the genetic variability of a population include mutations, natural selection, non-random mating, gene flow, and genetic drift (small population size).
64.3K
01:18Mutations in Microorganisms
728
Mutations are heritable changes in an organism’s genome involving alterations in the base sequence of DNA or RNA. These changes can influence cellular processes and phenotypic traits, potentially transforming the unaltered wild type into a mutant form. Such changes, termed forward mutations, are pivotal in shaping the genetic diversity of organisms.RNA viruses exhibit the highest mutation rates due to the absence of robust proofreading mechanisms during genome replication. In contrast,...
728
01:30Point and Frameshift Mutations
1.2K
Point mutations are genetic alterations involving the change of a single nucleotide base pair in DNA. Depending on how the alteration affects protein synthesis, they can lead to various consequences.Point mutations fall into the following types:Silent mutations occur when a nucleotide change does not alter the amino acid sequence due to the redundancy of the genetic code. For instance, changing ACC to ACA still encodes threonine, leaving the protein function unaffected. This occurs because...
1.2K