Maturation of testicular tissue from infant monkeys after xenografting into mice - PubMed (original) (raw)
Maturation of testicular tissue from infant monkeys after xenografting into mice
Rahul Rathi et al. Endocrinology. 2008 Oct.
Abstract
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 whether testicular maturation can also be induced in younger monkeys. Here we used testis tissue xenografting to investigate whether 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 pregnant mare serum gonadotropin and/or human chorionic gonadotropin twice weekly and were killed 28 weeks after 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, whereas those harvested from gonadotropin-treated mice contained elongated spermatids. Grafts from 3-month-old donors recovered from gonadotropin-treated mice contained pachytene spermatocytes, whereas 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 months 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.
Figures
Figure 1
Histological appearance of donor and grafted testis tissue. A, Three-month-old donor tissue. B, Six-month-old donor tissue. C, Graft from 3-month-old donor recovered from untreated mouse. D, Graft from 6-month-old donor recovered from untreated mouse. E, Graft from 3-month-old donor recovered from gonadotropin-treated mouse. F, Graft from 6-month-old donor recovered from gonadotropin-treated mouse. Arrows indicate spermatogonia in A–D, pachytene spermatocytes in E, and spermatids in F. Hematoxylin and eosin staining. Bar, 50 μm.
Figure 2
Expression of PCNA in donor and grafted tissue. A, Three-month-old donor tissue. B, Six-month-old donor tissue. C, Graft from 3-month-old donor recovered from untreated mouse. D, Graft from 6-month-old donor recovered from untreated mouse. E, Graft from 3-month-old donor recovered from gonadotropin-treated mouse. F, Graft from 6-month-old donor recovered from gonadotropin-treated mouse. Strong expression of PCNA was apparent in germ cells (arrow) in F. Bar, 50 μm.
Figure 3
Expression of MIS in donor and grafted tissue. A, Three-month-old donor tissue. B, Six-month-old donor tissue C, Graft from 3-month-old donor recovered from untreated mouse. D, Graft from 6-month-old donor recovered from untreated mouse. E, Graft from 3-month-old donor recovered from gonadotropin-treated mouse. F, Graft from 6-month-old donor recovered from gonadotropin-treated mouse. Expression is stronger in donor tissue and grafts recovered from untreated mice (A–D), compared with expression in grafts recovered from treated mice (E and F). Bar, 50 μm.
Figure 4
Expression of AR in donor and grafted tissue. A, Three-month-old donor tissue. B, Six-month-old donor tissue. C, Graft from 3-month-old donor recovered from untreated mouse. D, Graft from 6-month-old donor recovered from untreated mouse. E, Graft from 3-month-old donor recovered from gonadotropin-treated mouse. F, Graft from 6-month-old donor recovered from gonadotropin-treated mouse. AR expression was apparent in Leydig cells in donor tissue and grafts recovered from untreated mice (A-D, arrowheads) whereas AR was expressed strongly in Sertoli cells in grafts recovered from treated mice (E and F, arrows). Bar, 50 μm.
Figure 5
Spermatogonia identified by expression of UCH-L1 in donor and grafted tissue. A, Three-month-old donor tissue. B, Six-month-old donor tissue. C, Graft from 3-month-old donor recovered from untreated mouse. D, Graft from 6-month-old donor recovered from untreated mouse. E, Graft from 3-month-old donor recovered from gonadotropin-treated mouse. F, Graft from 6-month-old donor recovered from gonadotropin-treated mouse. Fewer spermatogonia were present in grafted tissue recovered from treated and untreated mice, compared with donor tissue. Bar, 50 μm.
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