Time course of female-to-male sex reversal in 38,XX fetal and postnatal pigs

In an attempt to understand the etiology of intersexuality in pigs, we thor oughly analyzed the gonads of 38,XX (SRY negative) female to male sex-rever sed animals at different developmental stages: during fetal life [50 and 70 days postcoitum (dpc)], just after birth [35 days postpartum (dpp)] and du ring adulthood. For each animal studied, we performed parallel histological and ultrastructural analyses on one gonad and RT-PCR analysis on the other gonad in order to define the expression profiles of sexually regulated gen es: SOX9, 3 beta -HSD, P450 aromatase, AAM, FOXL2, and Wnt4. Light and elec tron microscopic examination showed that testicular cords differentiated in XX sex-reversed gonads but were hypoplastic. Although the testicular cords contained gonia at the fetal stages, the germ cells had all died through a poptosis within a few weeks after birth. Ultrastructurally normal Leydig ce lls also differentiated, but later, and enclosed whorl-like residual bodies . At the fetal stages, three of the six genes studied in the intersex gonad s presented, as early as 50 dpe, a modified expression profile correspondin g to an elevated expression of SOX9 and the beginning of AMH and P450 aroma tase gene transcription. In addition to genes involved in the testicular pa thway, the same gonads expressed FOXL2, an ovarian-specific factor. The ova ries of true hermaphrodites were ineffective in ensuring correct folliculog enesis and presented abnormal expression profiles of ovarian specific genes after birth. These results indicate that the genes involved in this pathol ogy act very early during gonadogenesis and affect the ovary-differentiatin g pathway with variable expressivity from ovarian germ cell depletion throu gh to trans-differentiation into testicular structures. (C) 2001 Wiley-Liss , Inc.