Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers identify gene linked to sperm-producing stem cells in mammals

24.05.2004


Researchers have identified the first gene linked to the productivity of the stem cells that produce sperm in mammals. The discovery was made by applying the latest laboratory methods to a strain of mice restored from embryos frozen since the early 70s. The findings, which could someday have implications for infertility, contraception, and stem cell transplantation therapy, will be published in the June issue of Nature Genetics.



What researchers are trying to do is unravel the mystery of the adult germ stem cells in male testicles, which are capable of producing an average of 1,500 sperm during every human heartbeat – or an average of 130 million sperm a day.

"The average man will maintain a high level of sperm production from puberty onward, for decade after decade. To maintain that high a sperm output, you need many functioning stem cells. But the stem cells have to walk a tightrope and carefully balance the decision to become a sperm with the decision to stay a stem cell, so that the sperm output is maintained for all of these years," said Dr. Robert Braun, associate professor of genome sciences in the University of Washington School of Medicine.


The research was funded in part by the National Institute of Child Health and Human Development’s Contraceptive Development Research Centers Program.

Stem cells are cells that are not differentiated – that is, they have not acquired a particular type (such as lung cells, or blood cells). Researchers call stem cells ’pluripotent’ cells, meaning that any given stem cell can become any of several types. In the early embryo, embryonic stem cells give rise to all of the cell types in the organism, including adult stem cells, which continually replace cells in the adult tissues that die or differentiate into more mature cells like red blood cells. In the adult testicles, the germ stem cells can produce more germ stem cells, but can also produce daughter cells that go on to become sperm. But researchers do not know how the germ stem cells "decide" whether to create other germ stem cells or commit to becoming sperm. The workings of stem cells within the testicles are not well understood in mammals, though a few genes have been linked to stem cell self-renewal in the fruit fly, which has a simpler anatomical structure.

Braun’s laboratory studies mammals. One of his predoctoral students, Bill Buaas, was reading journal articles from decades ago when he came across a description of a mutant line of mice that originated in the 1950s. These mice were studied at the time for their limb deformities, but there was a passing reference in the literature to how the mice were fertile for a little while, but then became infertile. Buaas and Braun agreed that it sounded as if the mice were born with germ stem cells, the cells that produce sperm, but then lost their germ line early in puberty. After a series of tests, the researchers concluded that because of the mutation, the cells were more likely to convert from germ stem cells into sperm, than to produce more germ stem cells to keep the process going.

This luxoid strain of mice was first identified by Margaret C. Green of the University of Ohio. Green, a well-known mouse geneticist who died several years ago, had several embryos from the 35th generation of the mice frozen at the Jackson Laboratory in Maine, the world’s largest mutant mouse resource center. The UW researchers contacted The Jackson Laboratory for the embryos, and staff there brought the strain back to life after the 30-year freeze.

Back in the 70s, researchers were able to position the luxoid mutation on mouse chromosome 9. Using modern methods and the published mouse genome sequence, UW researchers were able to identify the mutation at a gene called ZFP145, which produces the protein PLZF. Using a fluorescent antibody against the PLZF protein, the researchers were able to show directly that PLZF is expressed in the adult germ stem cells. The researchers went on to show that another protein, OCT4, which functions to maintain the stem cells in the early embryo and in cultured embryonic stem cells, is also present in the adult germ stem cell. This important finding confirms earlier published studies suggesting that the adult germ stem cells are not far removed from embryonic stem cells.

Identification of the mutation may have significant effects for both infertility and contraception research. In terms of infertility, researchers may someday find a link between the gene and a gradual loss of germ cells within the human testes, Braun said. It’s possible that the mutation may tip the infertile man’s stem cells toward differentiation: their stem cells produce sperm for a while, and then are depleted and become infertile – as happens in the luxoid mice. In theory, that and other discoveries might be used to fashion a therapy to rescue human germ cells and maintain sperm production.

In the same way, any practical implications for contraceptive research are many years away, Braun said: "Luxoid appears to be important in the cells’ decision whether to remain a stem cell, or differentiate. If we can understand all the players then maybe we could develop a drug that could block the decision to become sperm – a contraceptive that would be reversible." However, Braun stressed that such products are many, many years away and will require considerable research.

Researchers also hope to someday be able to reverse the developmental process and create embryonic stem cells from adult germ stem cells. Embryonic stem cells are "more pluripotent" than adult stem cells. The embryonic stem cells could then be used in transplantation therapy in patients with degenerative diseases of other tissues.

Walter Neary | EurekAlert!
Further information:
http://www.washington.edu/

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften 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: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>