The development and anatomy of the gubernaculum in Hoxa11 knockout mice.

ABSTRACT

BACKGROUND: The gubernaculum is central to testicular descent, with recent evidence suggesting that it elongates to the scrotum like a limb bud. Homeobox (Hox) genes involved in limb bud outgrowth are expressed within the gubernaculum. Mice with homozygous Hoxa11 gene deletions have bilateral cryptorchidism. This study investigated the precise anatomical effects of Hoxa11 mutation on the mouse gubernaculum. METHODS: The pelvises of postnatal mice (n = 46; days 1-10) with Hoxa11 knockout (n = 19), heterozygotes (n = 11), and wild-type (n = 16) mice were serially sectioned and stained with hematoxylin and eosin. Immunohistochemistry was performed for the presence of desmin. RESULTS: Hoxa11 mutant mice had intraabdominal cryptorchid testes and highly convoluted vas deferentia. The gubernacular bulbs were abnormal, with no "outgrowth" and persistence of the prenatal "swelling reaction." Desmin immunostaining revealed the lack of undifferentiated mesenchymal cells usually seen as a "swirl" within the bulb and decreased formation of cremaster muscle. CONCLUSIONS: Hoxa11 may be involved in forming the growth center seen as the "swirl" of mesenchyme within the gubernacular bulb, consistent with these cells being required for gubernacular elongation during testicular descent. Hoxa11 mutations may well contribute to failure of gubernacular migration in boys with cryptorchidism.