Hoxa-10 deficient male mice exhibit abnormal development of the accessory sex organs.

Abstract

The role of mammalian Hox genes in regulating segmental patterning of axial structures and the limb is well established. A similar role in development of soft tissue organ systems has recently been suggested by observations linking several 5' members of the HoxA and HoxD clusters to segmentation events and morphogenesis in the gastrointestinal and genitourinary systems. We have specifically examined the role of Hoxa-10 in development of the male accessory sex organs by characterizing expression of Hoxa-10 in the developing male reproductive tract and correlating expression to morphologic abnormalities in knockout mice deficient for Hoxa-10 function. We report that Hoxa-10 expression in the Wolffian duct and urogenital sinus is regionally restricted and temporally regulated. The domain of expression is defined anteriorly by the caudal epididymis and extends posteriorly to the prostatic anlagen of the urogenital sinus. Expression was maximal at E18 and down-regulated postnatally, well before accessory sex organ morphogenesis is completed. Expression in the prostatic anlagen of the urogenital sinus cultured in vitro does not depend upon the presence of testosterone. Loss of Hoxa-10 function is associated with diminished stromal clefting of the seminal vesicles and decreased size and branching of the coagulating gland. The ductal architecture of the coagulating gland was altered in approximately 30% of mutants examined and suggests a partial posterior morphologic transformation of the coagulating gland. We interpret these data to indicate that Hoxa-10 is expressed in a region specific manner during late gestation and into the perinatal period and that Hoxa-10 is required for normal accessory sex organ development.