摘要：Ba c k g r o u n d: In utero exposure to endocrine-disrupting chemicals may contribute to testicular dysgenesis syndrome (TDS), a proposed constellation of increasingly common male reproductive tract abnormalities (including hypo spa dias, crypt orchidism, hypo spermato genesis, and testicular cancer). Male rats exposed in utero to certain phthalate plasticizers exhibit multi nucleated germ cell (MNG) induction and suppressed steroido genic gene expression and testosterone production in the fetal testis, causing TDS-consistent effects of hypo spa dias and crypt orchidism. Mice exposed to phthalates in utero exhibit MNG induction only. This disparity in response demonstrates a species-specific sensitivity to phthalate-induced suppression of fetal Leydig cell steroido genesis. Importantly, ex vivo phthalate exposure of the fetal testis does not recapitulate the species-specific endocrine disruption, demonstrating the need for a new bioassay to assess the human response to phthalates. oB j e c t i v e s: In this study, we aimed to develop and validate a rat and mouse testis xeno graft bio-assay of phthalate exposure and examine the human fetal testis response.Me t h o d s: Fetal rat, mouse, and human testes were xeno grafted into immuno deficient rodent hosts, and hosts were gavaged with a range of phthalate doses over multiple days. Xenografts were harvested and assessed for histopathology and steroidogenic end points.re s u l t s: Consistent with the in utero response, phthalate exposure induced MNG formation in rat and mouse xeno grafts, but only rats exhibited suppressed steroidogenesis. Across a range of doses, human fetal testis xeno grafts exhibited MNG induction but were resistant to suppression of steroido genic gene expression.co n c l u s i o n s: Phthalate exposure of grafted human fetal testis altered fetal germ cells but did not reduce expression of genes that regulate fetal testosterone biosynthesis
