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!
Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology
Migrating Cells: Folds in the cell membrane supply material for necessary blebs
23.11.2017 | Westfälische Wilhelms-Universität Münster
Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
23.11.2017 | Information Technology
23.11.2017 | Physics and Astronomy
23.11.2017 | Life Sciences