Development of neonatal mouse and fetal human testicular tissue as ectopic grafts in immunodeficient mice.
OBJECTIVE
To investigate the stepwise development and germ cell gene expression in allografted neonatal mouse testes and the differentiation of immature human testicular cells in xenografted human testes.


METHODS
Immunodeficient nude mice were used as hosts for allografting of neonatal mouse testes and xenografting of human fetal testicular tissues. Stepwise development and stage-specific gene expression of germ cells in allografts were systematically evaluated and parallel compared with those in intact mice by periodically monitoring the graft status with measurement of graft weight, histological analysis and determination of five stage-specific genes. Human testicular tissues from 20 and 26 weeks fetuses were used for the xenografting study. Histological analysis of xenografts was performed 116 and 135 d after the grafting procedure.


RESULTS
In the allografting study, progressive increase in tissue volume and weight as well as in tubule diameter in grafts was observed; the appearance time of various germ cells in seminiferous tubules, including spermatogonia, spermatocytes, round and elongate spermatids and sperm, was comparable with that in intact donors; the initiation of gene transcription in grafts showed a similar trend as in normal mice. Graft weight ceased to increase after 7-8 weeks and degradation of grafts was observed after 5 weeks with progressive damage to seminiferous epithelium. In the xenografting study using immature human testicular tissues, graft survival and development was indicated by increasing graft weight, Sertoli cells differentiation into advanced stage, germ cells migration and location to the basal lamina and formation of a niche-like structure.


CONCLUSIONS
The developmental course and gene expression pattern of germ cells in allografts were similar to those in intact mice. The best time point for retrieval of mouse sperm from grafts was 5-7 weeks after grafting procedure. An accelerated development of immature human testicular cells could be achieved by ectopic xenografting of human testes.
Yu
Jie
J
Central Laboratory, Peking University Shenzhen Hospital, Shenzhen 518036, China.
Cai
Zhi-Ming
ZM
Wan
Hui-Juan
HJ
Zhang
Fang-Ting
FT
Ye
Jing
J
Fang
Jia-Zhi
JZ
Gui
Yao-Ting
YT
Ye
Jiong-Xian
JX
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D017931:DNA Primers; D020869:Gene Expression Profiling; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013737:Testis / Q000254:growth & development* / Q000378:metabolism
D017931:DNA Primers