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Disorders of sex development (DSDs) and the testicular dysgenesis syndrome (TDS) seem to result from maldevelopment of the fetal testis. TDS seems to be associated with the development of testicular germ cell tumors in young adulthood. Current knowledge of normal and disrupted testicular development has been largely derived from rodent models. Immature testis tissue from several primate species has been grafted into a nude mouse host, resulting in full spermatogenesis in the grafted tissue. However, rodents do not develop testicular germ cell tumors equivalent to those occurring in human beings, suggesting fundamental differences in fetal testis development between primates and rodents. Previous studies show limited survival of human testis xenografts when postnatal tissue is grafted. The lack of an appropriate human model system has hampered efforts to study mechanisms of human germ cell differentiation and to investigate the origins of DSDs and TDS.The present study evaluated the use of human fetal testis xenografting as a technique to recapitulate normal fetal testis development and differentiation.First-trimester (9 weeks, n ϭ 4) and second-trimester (14-18 weeks, n ϭ 6) human fetal testes were grafted into castrated male nude mice for 6 weeks. Mice with second-trimester xenografts were treated with human chorionic gonadotropin (hCG), or received 0.9% saline or the vehicle 7 days after the graft. Immunohistochemistry, triple immunofluorescence, and testosterone assay were used for quantification of germ cell differentiation and proliferation. Cellular development and function within the xenografts were compared with those of age-matched controls.Graft survival rates were Ͼ75% with normal morphology. Seminiferous cord formation was initiated in the first-trimester xenografts. Expression of cell-specific and differentiation-specific protein markers in first-and second-trimester grafts demonstrated normal functional development of Sertoli, Leydig, and peritubular myoid cells. Differentiation and functional activation of Leydig cells in second-trimester hCG-exposed grafts indicated induction of steroidogenesis. In hosts bearing second-trimester xenografts, treatment with hCG resulted in nearly a 10-fold increase in serum testosterone levels compared with vehicle-treated hosts. Germ cell differentiation during the grafting period was similar to that occurring normally in the intact testis and was equivalent to that of age-matched controls This was established by quantification of the loss of expression of the gonocyte pluripotency marker OCT4 after grafting coincident with emerging expression of the protein VASA, which is associated with normal differentiation into prespermatogonia.These findings suggest that this in vivo system has the potential to investigate mechanisms of normal human fetal testis development and to study mechanisms of disruption associated with DSDs and TDS or with exposure to environmental chemicals and other exogenous factors. EDITORIAL COMMENT(For the most part, the reports in the SURVEY ha...

Elevated serum progesterone levels on the day of hCG administration is associated with reduced ongoing pregnancy rates. In particular, serum progesterone levels of >1.5 ng/ml were associated with lower ongoing pregnancy rates following IVF/ICSI cycles irrespective of the GnRH analogue used for pituitary down-regulation.

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