Defects of prostate development and reproductive system in the estrogen receptor-α null male mice

The estrogen receptor-α knockout (ERαKO, ERα ^-I-) mice were generated via the Cre-loxP system by mating floxed ERα mice with β-actin (ACTB)-Cre mice. The impact of ERα gene deletion in the male reproductive system was investigated. The ACTB-Cre/ERα^-I- male mice are infertile and have lost 90% of epididymal sperm when compared with wild-type mice. Serum testosterone levels in ACTB-Cre/ERα^-I- male mice are 2-fold elevated. The ACTB-Cre/ERα^-I- testes consist of atrophic and degenerating seminiferous tubules with less cellularity in the disorganized seminiferous epithelia. Furthermore, the ventral and dorsal-lateral prostates of ACTB-Cre/ERα^-I- mice display reduced branching morphogenesis. Loss of ERα could also be responsible for the decreased fibroblast proliferation and changes in the stromal content. In addition, we found bonemorphogenetic protein, a mesenchymal inhibitor of prostatic branching morphogenesis, is significantly up-regulated in the ACTB-Cre/ERα ^-I- prostates. Collectively, these results suggest that ERα is required for male fertility, acts through a paracrine mechanism to regulate prostatic branching morphogenesis, and is involved in the proliferation and differentiation of prostatic stromal compartment.