The spermatogonial stem cells (SSCs) are
responsible for producing sperm. Sperm are constantly replenished in the adult male body.
Understanding the workings of stem cells responsible for this
replenishment is expected to shed light on why male fertility diminishes
with age, and possibly lead to new treatments for infertility.
"So-called Myc genes play an important role in stem cells' ability to
self-renew," explains Kyoto University's Takashi Shinohara, who is
interested specifically in SSCs. Shinohara adds that SSCs are unique,
because they are "the only stem cells that transmit genetic information
to offspring."
‘The Myc genes play an important role in stem cells' ability to self-renew. These findings could have important implications for infertility research in the future.’
In a new report in
Genes & Development, the Shinohara lab
demonstrates how the Myc gene regulates the self-renewal of mouse SSCs,
via a process of glycolysis control. Glycolysis is a key part of cells'
energy-making mechanism.
The scientists injected two types of SSCs into mouse testes: normal
cells in some, and Myc gene-suppressed in others. Two months later, they
found that the total number of abnormal SSCs was far fewer than normal
ones. Gene analysis showed that the capacity for self-renewal had been
compromised, with possibly important implications for sperm production
in these mice.
"We found changes in the expression of genes that would slow the cell cycle," says Shinohara.
In other words, suppressed SSCs could self-renew, but at a slower
than normal rate. Further study showed that this diminished rate was
accompanied by impaired glycolysis, suggesting that the cells were not
generating sufficient energy.
"A difference in glycolysis could explain natural differences in SSC
self-renewal between mice," elaborates Mito Kanatsu-Shinohara,
first-author of the paper. "DBA/2 and B6 are two mouse types in which
SSCs are know to self-renew at different rates."
Further experiments confirmed that glycolysis was more active in the
cells of DBA/2 mice. Moreover, isolating cells from B6 mice and treating
them with certain chemicals that enhanced glycolysis could increase the
proliferation rate to levels comparable with DBA/2.
"These findings could have important implications for infertility
research in the future," says Shinohara. "Stimulating the metabolism of
SSCs could improve their proliferation. However, more careful study of
the molecular pathways is necessary."
Source: Eurekalert
Careers
