Developmental disorders of the reproductive tract in C57BL/6N-XY^POS mice

Mammalian embryos possess undifferentiated gonads and primordial male and female reproductive tracts. In males, sex-determining region of the Y chromosome (Sry) triggers the differentiation of gonadal supporting cell precursors into Sertoli cells. In C57BL/6N-XY^POS (B6N-XY^POS) mice, a model of disorders of sex development, Sry expression is delayed relative to wild-type B6N mice, and several reproductive tract malformations have been reported. In this study, we investigated the developmental stage and regions at which reproductive tract development fails in B6N-XY^POS. In B6N-XY^POS at 15.5 days post-coitum (dpc), the number of seminiferous tubules showed no difference from B6N, but seminiferous tubules with closed at both ends appeared. In B6N-XY^POS with bilaterally developed ovaries or testes, significant disorders were observed only in the female reproductive tract. B6N-XY^POS ovotestes showed impaired testis differentiation in the cranial and caudal regions, not only in fetuses but also in adults. In female B6N-XY^POS with bilaterally or unilaterally formed ovaries, the Müllerian ducts opened into the urogenital sinus at 15.5 dpc; however, at postnatal day 1, one individual exhibited a uterus with a closed region, and many adult females formed an edematous uterus. These results suggest that impaired cranial testis differentiation may disrupt the connection between the seminiferous tubules and the rete testis. They also suggest that Müllerian duct formation is initially completed even in female B6N-XY^POS with an edematous uterus, but that the duct closes abnormally between 15.5 dpc and birth.