Out of gas and low on sperm? Team uncovers genetic key to self-renewal of reproductive cells

December 27, 2016
Finding a genetic key for sperm-producing stem cells in mice. Credit: Kyoto University

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 spermatogonial stem cells (SSCs), which are responsible for producing sperm. Shinohara adds that SSCs are unique, because they are "the only that transmit genetic information to offspring."

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: 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 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."

Explore further: Sorting out fertility after childhood cancer

More information: Mito Kanatsu-Shinohara et al, Myc/Mycn-mediated glycolysis enhances mouse spermatogonial stem cell self-renewal, Genes & Development (2016). DOI: 10.1101/gad.287045.116

Related Stories

Sorting out fertility after childhood cancer

March 15, 2013
As success rates in treating childhood cancers have improved, greater emphasis is being placed on quality of life issues following successful treatment. Many cancer treatments can lead to infertility, but there are few methods ...

Recommended for you

A rogue gene is causing seizures in babies—here's how scientists wants to stop it

July 26, 2017
Two rare diseases caused by a malfunctioning gene that triggers seizures or involuntary movements in children as early as a few days old have left scientists searching for answers and better treatment options.

Scientists provide insight into genetic basis of neuropsychiatric disorders

July 21, 2017
A study by scientists at the Children's Medical Center Research Institute at UT Southwestern (CRI) is providing insight into the genetic basis of neuropsychiatric disorders. In this research, the first mouse model of a mutation ...

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

Late-breaking mutations may play an important role in autism

July 17, 2017
A study of nearly 6,000 families, combining three genetic sequencing technologies, finds that mutations that occur after conception play an important role in autism. A team led by investigators at Boston Children's Hospital ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.