Early orchiopexy restores fertility in the Hoxa 11 gene knockout mouse

Abstract

Purpose: We investigated whether infertility could be reversed in cryptorchid mice (with disrupted expression of the homeobox gene Hoxa 11) by orchiopexy and mating such animals with females of proven fertility.

Materials and methods: Hoxa 11 mutant and WT male mice were genotyped by polymerase chain reaction. Surgery (orchiopexy or sham operation) was performed at age 18 days and fertility was assessed at ages 6 to 8 weeks. Animals were sacrificed at ages 6 to 9 months and computer assisted semen analysis was performed on fluid obtained by epididymal puncture.

Results: Five of 28 mutant mice proved fertile following orchiopexy versus 0 of 22 after sham operation (p <0.05). Values in WT mice were 18 of 35 and 25 of 33, respectively (p <0.01). Mean spermatozoa counts +/- SEM were 21.7 +/- 5.9 x 106/ml in 8 mutant mice with orchiopexy, 2.78 +/- 1.59 x 106/ml in 8 sham operated mutant mice (p <0.002), 15.6 +/- 4.9 x 106/ml in 7 WT mice with orchiopexy and 36.3 +/- 10.5 x 106/ml in 9 sham operated WT mice (p <0.02).

Conclusions: Testicular position following orchiopexy is important to achieve fertility but the surgical procedure was associated with a degree of damage. Since mutant animals did not attain the fertility rates observed in WT animals following orchiopexy, other factors (possibly vaso-epididymal) may be necessary for normal spermatogenesis. Further studies of this model may allow the identification of such factors.