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Ontogenesis of female‐to‐male sex‐reversal in XX polled goats

The association of polledness and intersexuality in domestic goats (PIS mutation) made them a practical genetic model for studying mammalian female‐to‐male sex reversal. In this study, gonads from XX sex‐reversed goats (PIS‐/‐) were thoroughly characterized at the molecular and histologic level from the first steps of gonadal differentiation (36 days post coitum [dpc]) to birth. The first histologic signs of gonadal sex reversal were detectable between 36 and 40 dpc (4–5 days later than the XY male) and were mainly characterized by the reduction of the ovarian cortex and the organization of seminiferous cords. As early as 36 dpc, aromatase (CYP19) gene expression was decreased in XX (PIS‐/‐) gonads, whereas genes normally up‐regulated in males, such as SOX9 and AMH, showed an increased expression level from 40 dpc. Thereafter, steroidogenic cell precursors were affected, and at 56 dpc, WNT4 and 3β‐HSD were expressed in a male‐specific manner in sex‐reversed gonads. Another noticeable feature was a progressive disappearance of germ cells, clearly visible in testicular cords around 70 dpc where 50–75% of germ cells were absent in XX (PIS‐/‐) gonads. These observations indicated that the causal mutation of PIS acts very early in the sex‐determining cascade and affects primarily the supporting cells of the gonad. © 2002 Wiley‐Liss, Inc.