Biomedical Engineering Reference
In-Depth Information
Chapter 9
Regenerative Potential of Spermatogenesis
after Gonadotoxic Therapies
Gunapala Shetty, Gensheng Wang, and Marvin L. Meistrich
Abstract
Gonadotoxic therapies, particularly radiation and chemotherapy used
in the treatment of cancer, are extremely damaging to spermatogenesis. They may
result in prolonged or permanent oligospermia or azoospermia and consequent
infertility. Transient oligo- or azoospermia is generally observed due to killing
of the rapidly proliferating differentiating spermatogonia. High doses of some
of these agents can also kill spermatogonial stem cells, but their sensitivity to
killing by different agents varies with the species. Any surviving stem cells may
repopulate the tubules and produce differentiating spermatogenic cells and restore
fertility. However the kinetics of this process, which has been studied in mice, rats,
monkeys, and humans, is generally gradual, again showing wide variation between
species. There are no universal methods to enhance the regeneration of spermato-
genesis from the surviving stem cells, but suppression of testosterone and possibly
gonadotropins enhances the recovery process in rodents. An understanding of the
mechanisms controlling this regenerative process and how the results might be
applied to humans is needed.
Keywords
Spermatogonia • Radiation • Chemotherapy • Stem cells
• Regeneration
9.1
Introduction
Chemotherapy and radiotherapy used in the treatment of cancer, in some autoim-
mune and kidney diseases, and in other nonmalignant disorders can cause long-
term or permanent gonadal toxicity in male patients. For children and young adults
M.L. Meistrich (
*
)
Department of Experimental Radiation Oncology, Unit 066, The University of Texas M.D.
Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA
e-mail: meistrich@mdanderson.org
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