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.