By Paul Candon
A new treatment for male infertility now being tested in animals
may one day help men who currently are unable to father children.
Philadelphia scientists have found a way to extract germ cells --
undeveloped sperm cells -- from one type of infertile mice and
implant them in the testes of other mice, allowing the germ cells
to develop into functional sperm cells.
Impaired sperm development is believed to account for about 40
percent of all human infertility cases. The new technique may be
useful in allowing males who have cancer therapy while still boys
to father children later on.
The investigators obtained the germ cells from Steel mice, a
mouse strain that is infertile. These mice have germ cells that do
not undergo spermatogenesis -- the process by which germ cells
become mature sperm.
The germ cells from the Steel mice were implanted in the testes
of another mouse strain called white spotting mice. These mice are
also infertile and lack germ cells. However, white spotting mice
retain a proper testicular environment that would allow germ cells
to mature.
The research team was headed by Dr. Ralph Brinster, a veterinary
scientist at the University of Pennsylvania in Philadelphia.
Following the implantation procedure, about 80 percent of the
once-infertile recipient white spotting mice had viable sperm. Of
nine mice who then mated with normal females, four produced
offspring. The resulting progeny were the offspring of the Steel
mice, the mice that donated the germ cells.
The report is published in the January issue of the journal
Nature Medicine (http://medicine.nature.com).
Brinster developed the technique for extracting and implanting
germ cells in the early 1990s. To successfully implant germ cells
into a male, he said, you need only about one percent of the number
of germ cells normally found in the donor male. ``It's a very
powerful cell,'' he explained.
He added that, instead of donating germ cells that would develop
in a second male, another way to treat problems with sperm
development is to adjust the testicular environment to make it more
conducive to spermatogenesis.
In men who cannot produce sperm, a genetic defect is the cause
about 10 percent of the time, according to Dr. Howard Cooke, from
the MRC Human Genetics Unit, and Dr. Philippa Saunders, from the
MRC Reproductive Biology Unit at the Western General Hospital in
Edinburgh, Scotland. Cooke and Saunders authored an editorial that
accompanied the article in Nature Medicine.
``The ability to isolate, culture and reintroduce germ cells
suggests the potential for gene therapy approaches to correct germ
cell genetic lesions,'' they wrote. However, ``a practical problem
is posed by the fact that most cases of infertility are due to
unknown causes, genetic or otherwise.''
Another problem, they pointed out, is that most countries
prohibit gene therapy with human germ cells due to ethical
considerations.
However, Cooke and Saunders noted that a treatment similar to
the one used by Brinster and colleagues might be useful in helping
male childhood cancer survivors have children. Many cancer
treatments kill germ cells, leaving these cancer survivors
infertile.
``Cryopreservation of sperm, a successful strategy in the
management of adult cancer sufferers, is not available to
pre-pubertal boys,'' they wrote. ``The alternative,
cryopreservation of testicular stem cells and post-treatment
reintroduction, could protect germ cells from potentially mutagenic
cancer treatments and safeguard against infertility.''
