Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Gene defects could be new cause of male infertility

18.10.2007
Scientists at the University of North Carolina at Chapel Hill have identified a gene crucial to the final step of the formation of a functional sperm cell.

That final step – called spermiogenesis – entails the compaction of DNA into a tight ball within the head of the sperm so it can successfully penetrate an egg.

Mice engineered to lack the crucial gene, Jhdm2a, that triggers this process did not produce many mature sperm, and those they did produce had abnormally shaped heads and immotile tails.

“Defects in this gene could be the cause for some cases of male infertility,” said study senior author Yi Zhang, Ph.D., Howard Hughes Medical Institute investigator and professor of biochemistry and biophysics in the UNC School of Medicine. Zhang is also a member of the UNC Lineberger Comprehensive Cancer Center.

... more about:
»DNA »Histone »Jhdm2a »cause »defect »infertility »sperm

“Because this gene has a very specific effect on the development of functional sperm, it holds great potential as a target for new infertility treatments that are unlikely to disrupt other functions within the body.”

The study, published on-line in the journal Nature Wednesday (Oct. 17, 2007), provides evidence that Jhdm2a directly controls expression of several genes required for DNA packaging in sperm cells. The research was funded by the Howard Hughes Medical Institute and the National Institutes of Health. For a sperm cell to mature fully, multiple molecular events have to occur, such as assembly of a sperm tail and packaging of sperm DNA.

In the sperm cell, yarn-like strands of DNA wrap around spools of protein called histones that package the DNA so it fits into the nucleus. Chemical tags such as methyl groups affixed to the histones govern how tightly the DNA can be packaged, affecting the accessibility for the gene to be switched on or off.

Previous studies have shown that when a gene is turned off, one of these histones, H3K9, carries a methyl tag. In a study published in Cell last year, Zhang’s laboratory demonstrated that the enzyme Jhdm2a removes this methyl tag, allowing the gene to become switched on, or expressed.

“Although a number of histone demethylases have been identified, very little is known regarding their biological functions, particularly in the context of whole animals,” said Yuki Okada, Ph.D., a postdoctoral fellow in Zhang’s laboratory and lead author on the study.

The unique expression pattern of Jhdm2a suggests that this demethylase may play an important role in the late stages of sperm cell development. In this study, mice genetically engineered to lack this gene had smaller testes, a significantly lower sperm count, and were infertile.

In addition, the few sperm that were produced by these mutant mice displayed significant morphological defects, including abnormally shaped heads and immotile tails.

To assess the packaging state of the sperm DNA, the researchers used electron microscopy and a fluorescent dye called acridine orange, which fluoresces differently depending on the packaging state of a sperm. Both techniques revealed a defect in sperm DNA packaging in the mutant mice, suggesting that incomplete DNA packaging was the cause of infertility.

“There are several mouse models that exhibit the male infertility seen in human syndromes such as azoospermia (absence of sperm) or globozoospermia (sperm with round heads),” said Zhang, “However, most of the genes required for normal spermatogenesis in mice are intact in human patients, raising the possibility that we might consider the jhdm2a gene as a culprit in these human male infertility syndromes.”

Zhang and his colleagues are now looking for mutations in this gene in infertility patients, and are also interested in identifying the partners or cofactors in the cell that help this gene do its job.

Les Lang | EurekAlert!
Further information:
http://www.med.unc.edu

Further reports about: DNA Histone Jhdm2a cause defect infertility sperm

More articles from Life Sciences:

nachricht Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg

nachricht Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Attoseconds break into atomic interior

A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.

In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...

Im Focus: Good vibrations feel the force

A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.

By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...

Im Focus: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Basque researchers turn light upside down

23.02.2018 | Physics and Astronomy

Finnish research group discovers a new immune system regulator

23.02.2018 | Health and Medicine

Attoseconds break into atomic interior

23.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>