Aetiology of intersexuality in female (XX) pigs, with novel molecular interpretations

This review considers the problem of ovotestis formation in animals of 38,XX chromosome complement. After a clinical description, attention focuses on the condition of the gonads and genital tract. A complete spectrum of gonadal types has been found, ranging from a single ovotestis almost invariably on the right-hand side to both gonads appearing as testicular-like structures, sometimes with a distinct tunica albuginea. The ovotestis or testis-like structure may have descended to an inguinal or scrotal location. Although interstitial cells of Leydig and seminiferous tubules were always abundant in testicular tissue, germ cells were never present. The lumen of the seminiferous tubules was packed with pale-staining, Sertoli-like cells. A bicornuate uterus was characteristic but suppression of the proximal portion of the Müllerian duct always adjoined an ovotestis; a corresponding development of the Wolffian duct featured as a convoluted epididymis. Inhibition of the Fallopian tube was attributed to a local influence of AMH from the Sertoli cells, as was the failure of small Graafian follicles within an ovotestis to respond to injected gonadotrophins. As to the aetiology of an ovotestis, defective colonisation of the genital ridges by primordial germ cells is considered, as is evidence for incorporation of adrenal cells into the embryonic gonad. Molecular probing has failed to reveal the classical sex-determining gene, Sry, and other Y-related DNA sequences such as Zfy and DYZI in almost all the intersex animals examined. Currently favoured as an explanation for ovotestis formation is a mutation in the inhibin gene within granulosa cells of Graafian follicles. Such a mutation would prompt secretion of the closely comparable glycoprotein molecule AMH in these genetic females, with a resultant progressive virilisation of gonadal tissue. The proposed mutation may be carried as an autosomal recessive gene by certain boars. Varying amounts of AMH secretion or differing timescales for the transition from inhibin to AMH could in part explain differing degrees of ovotestis formation. Despite this proposition, interactions between genes that prescribe functional testicular tissue, enhanced rates of gonadal development, and left-right asymmetries between the paired gonads now require systematic study.