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,” said Dr. Diego H. Castrillon, Associate Professor of Pathology and Director of Investigative Pathology. “The PAX7 stem cells we 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 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. Dr. Castrillon and his team tracked progenitor cells that express the protein PAX7 in mouse testes, and found that these cells gradually give rise to mature sperm.
“We 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,” said Dr. Castrillon, who holds the John H. Childers, M.D. Professorship in Pathology. “Our 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.
First author Gina Aloisio, a student in UT Southwestern’s Medical Scientist Training Program, is the recipient of a Fellowship Award from the UT Southwestern Cecil H. and Ida Green Center for Reproductive Biology Sciences. Other UT Southwestern researchers involved in the work include Dr. Kent Hamra, Assistant Professor of Pharmacology; Dr. James Amatruda, Associate Professor of Pediatrics, Internal Medicine, and Molecular Biology, the Horchow Family Scholar in Pediatrics and holder of the Nearburg Family Professorship in Pediatric Oncology Research; Dr. Anita Sengupta, Assistant Professor of Pathology; Dr. Ileana Cuevas, Instructor of Pathology; Dr. Yuji Nakada, Instructor of Pathology; Abhijit Bugde, Department of Cell Biology; graduate student researchers Hatice Saatcioglu, Christopher Peña, and Hema Manjunath; and former UT Southwestern researchers Dr. Michael Baker, Dr. Edward Tarnawa, and Jishnu Mukherjee.
The work was sponsored by the David M. Crowley Foundation with additional support through grants from the National Cancer Institute and the State of Texas Norman Hackerman Advanced Research Program.
UT Southwestern’s Harold C. Simmons Cancer Center is the only National Cancer Institute-designated cancer center in North Texas and one of just 66 NCI-designated cancer centers in the nation. The Harold C. Simmons Cancer Center includes 13 major cancer care programs with a focus on treating the whole patient with innovative treatments, while fostering groundbreaking basic research that has the potential to improve patient care and prevention of cancer worldwide. In addition, the Center’s education and training programs support and develop the next generation of cancer researchers and clinicians.
About UT Southwestern Medical Center
UT Southwestern, one of the premier academic medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty includes many distinguished members, including six who have been awarded Nobel Prizes since 1985. Numbering more than 2,700, the faculty is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to nearly 91,000 hospitalized patients and oversee more than 2 million outpatient visits a year.
Media Contact: Russell Rian
Russell Rian | Eurek Alert!
Locusts provide insight into brain response to stimuli, senses
28.04.2015 | Washington University in St. Louis
Discovery of an unexpected function of a protein linked to neurodegenerative diseases
28.04.2015 | Institute for Research in Biomedicine (IRB Barcelona)
KAIST researchers published an article on the development of a novel technique to precisely track the 3-D positions of optically-trapped particles having complicated geometry in high speed in the April 2015 issue of Optica.
Daejeon, Republic of Korea, April 23, 2015--Optical tweezers have been used as an invaluable tool for exerting micro-scale force on microscopic particles and...
A very small and rare species of shark is swimming its way through scientific literature. But don't worry, the chances of this inches-long vertebrate biting...
Ever since computers have been small enough to be fixtures on desks and laps, their central processing has functioned something like an atomic Etch A Sketch, with electromagnetic fields pushing data bits into place to encode data.
Unfortunately, the same drawbacks and perils of the mechanical sketch board have been just as pervasive in computing: making a change often requires starting...
How is lightning initiated in thunderclouds? This is difficult to answer - how do you measure electric fields inside large, dangerously charged clouds? It was discovered, more or less by coincidence, that cosmic rays provide suitable probes to measure electric fields within thunderclouds. This surprising finding is published in Physical Review Letters on April 24th. The measurements were performed with the LOFAR radio telescope located in the Netherlands.
How is lightning initiated in thunderclouds? This is difficult to answer - how do you measure electric fields inside large, dangerously charged clouds? It was...
Max Planck researcher Buhalqem Mamtimin determines how much nitrogen oxide is released into the atmosphere from agriculturally used oases.
In order to make statements about current and future air pollution, scientists use models which simulate the Earth’s atmosphere. A lot of information such as...
23.04.2015 | Event News
23.04.2015 | Event News
13.04.2015 | Event News
28.04.2015 | Press release
28.04.2015 | Power and Electrical Engineering
28.04.2015 | Earth Sciences