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.
“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!
Molecular Force Sensors
20.09.2017 | Max-Planck-Institut für Biochemie
Foster tadpoles trigger parental instinct in poison frogs
20.09.2017 | Veterinärmedizinische Universität Wien
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...
Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!
When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...
For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.
Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.
MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...
Pathogenic bacteria are becoming resistant to common antibiotics to an ever increasing degree. One of the most difficult germs is Pseudomonas aeruginosa, a...
19.09.2017 | Event News
12.09.2017 | Event News
06.09.2017 | Event News
20.09.2017 | Life Sciences
20.09.2017 | Power and Electrical Engineering
20.09.2017 | Physics and Astronomy