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Submitted on March 5, 2008
Accepted on June 12, 2008
Center for Animal Transgenesis and Germ Cell Research, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA 19348, USA; Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, CA 95616, USA; and Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA
* To whom correspondence should be addressed. E-mail: dobrinsk{at}vet.upenn.edu.
In juvenile monkeys, precocious puberty can be induced by administration of gonadotropins resulting in testicular somatic cell maturation and germ cell differentiation. It is, however, unknown if testicular maturation can also be induced in younger monkeys. Here, we used testis tissue xenografting to investigate if infant monkey testis tissue will undergo somatic cell maturation and/or spermatogenesis in response to endogenous adult mouse gonadotropins or exogenous gonadotropins. Testicular tissue pieces from 3- and 6-month-old rhesus monkeys were grafted to immunodeficient, castrated mice. Recipient mice were either left untreated or treated with PMSG and/or hCG twice weekly, and were sacrificed 28 weeks post-grafting. Testicular maturation in grafted tissue was assessed based on morphology and the most advanced germ cell type present, and by immunohistochemistry for expression of proliferating cell nuclear antigen, Mullerian inhibiting substance and androgen receptor. Testis grafts, irrespective of donor age or treatment, contained fewer germ cells than donor tissue. Grafts from 6-month-old donors showed tubular expansion with increased seminiferous tubule diameter and lumen formation while those harvested from gonadotropin-treated mice contained elongated spermatids. Grafts from 3-month-old donors recovered from gonadotropin-treated mice contained pachytene spermatocytes, while those recovered from untreated mice showed only slight tubular expansion. Immunohistochemistry revealed that exposure to exogenous gonadotropins supported Sertoli cell maturation, irrespective of donor age. These results indicate that sustained gonadotropin stimulation of immature (<12-month-old) monkey testis supports Sertoli cell maturation, thereby terminating the unresponsive phase of the germinal epithelium and allowing complete spermatogenesis in testis tissue from infant rhesus monkeys.
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