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Hypodactyly (Hoxa13(Hd)) mice have a 50-base-pair deletion in Hoxa13, and rare surviving homozygotes of both sexes are infertile. Heterozygous mutant mice are fertile; however, Hoxa13(Hd/+) females exhibit an anterior transformation of cervical tissue to a uterine stromal phenotype that is accentuated in the homozygote and occasionally includes uterine-specific glands in the transformed cervical region. The columnar-to-squamosal epithelial transition that characterizes mature cervical-vaginal tissue is positioned within uterine-like stroma rather than cervical tissue in these mutants, suggesting that this postnatal developmental transition occurs independent of the underlying stromal characteristics. Hoxa13(Hd/Hd) adult females produce apparently functional germ cells as determined by superovulation and ovarian histology, but they exhibit profound hypoplasia of the cervix and vaginal cavity. Using whole-mount in situ hybridization, we localized Hoxa13 expression to the cervical and vaginal tissues, consistent with the observed defects. In Hoxa13(Hd/Hd) males, the penian bone is severely hypoplastic and misshapen. The penian bone develops by a combination of endochondral and intramembranous ossification, but the defects observed in Hoxa13(Hd/Hd) males are limited to the region of endochondral bone formation. Our results indicate that infertility in Hypodactyly mutants is related to hypoplasia of the vaginal cavity and cervix in females and deficiency of the os penis in males.

Infertility in Adult Hypodactyly Mice Is Associated with Hypoplasia of Distal Reproductive Structures1