Scientists discover cancer treatment resistant sperm stem cells in testis.


Rare stem cells in testis that produce a biomarker protein called PAX7 help give rise to new sperm cells, and may hold a key to restoring fertility, research by scientists at UT Southwestern Medical Center suggests.

Researchers studying infertility in mouse models found that, unlike similar types of cells that develop into sperm, the stem cells that express PAX7 can survive treatment with toxic drugs and radiation. If the findings hold true in people, they eventually could lead to new strategies to restore or protect fertility in men undergoing cancer treatment.

Unfortunately, many cancer treatments negatively impact fertility, and men who receive such treatments are at high risk of losing their fertility. This is of great concern among cancer patients.  The PAX7 stem cells identified proved highly resistant to cancer treatments, suggesting that they may be the cells responsible for the recovery of fertility following such treatments.

Infertility, which the Centers for Disease Control estimates affects as many as 4.7 million men in the United States, is a key complication of cancer treatments, such as chemotherapy and radiation therapy.

The new findings, presented in the opensource Journal of Clinical Investigation, provide valuable insight into the process of sperm development. Known as spermatogenesis, sperm development is driven by a population of immature stem cells called progenitors in the testes. These cells gradually mature into fully differentiated sperm cells.  The team tracked progenitor cells that express the protein PAX7 in mouse testes, and found that these cells gradually give rise to mature sperm.

The medical community have long known that male fertility is driven by rare stem cells within the testes, but the precise identity of these stem cells has been disputed.  The findings suggest that these rare PAX7 cells are the key cells within the testes that are ultimately responsible for male fertility.

Importantly, even after exposure to toxic chemotherapy or radiation treatments, the PAX7-expressing cells continued to divide and thus could contribute to restoring sperm development.

Source:  The University of Texas Southwestern Medical Center

 

PAX7+ spermatogonia in normal testes.  Rarity of PAX7+ cells in adult (6-week-old) testis cross-section. Arrow denotes a PAX7+ cell within a single seminiferous tubule.  KIT and PAX7 double-labeling (confocal microscopy) showed that PAX7+ spermatogonia (arrow) were isolated (i.e., Asingle) and KIT–. No KIT+PAX7+ spermatogonia were observed. PAX7 was nuclear, whereas KIT was membrane-associated, as expected. Image shows 3 tubules optically sectioned close to the level of the basement membrane to visualize large numbers of spermatogonia.  PAX7 expression defines germline stem cells in the adult testis.  Aloisio et al 2014.

PAX7+ spermatogonia in normal testes. Rarity of PAX7+ cells in adult (6-week-old) testis cross-section. Arrow denotes a PAX7+ cell within a single seminiferous tubule. KIT and PAX7 double-labeling (confocal microscopy) showed that PAX7+ spermatogonia (arrow) were isolated (i.e., Asingle) and KIT–. No KIT+PAX7+ spermatogonia were observed. PAX7 was nuclear, whereas KIT was membrane-associated, as expected. Image shows 3 tubules optically sectioned close to the level of the basement membrane to visualize large numbers of spermatogonia. PAX7 expression defines germline stem cells in the adult testis. Aloisio et al 2014.

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