Defects of Prostate Development and Reproductive System in the Estrogen Receptor-α Null Male Mice

The estrogen receptor-α knockout (ERαKO, ERα−/−) 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−/− male mice are infertile and have lost 90% of epididymal sperm when compared with wild-type mice. Serum testosterone levels in ACTB-Cre/ERα−/− male mice are 2-fold elevated. The ACTB-Cre/ERα−/− 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−/− 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 bone morphogenetic protein, a mesenchymal inhibitor of prostatic branching morphogenesis, is significantly up-regulated in the ACTB-Cre/ERα−/− 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. Newly generated ACTB-Cre/Estrogen receptor alpha knockout (ERα-/-) male mice show that ERα acts through a paracrine mechanism to regulate prostatic branching morphogenesis and is involved in the proliferation and differentiation of prostatic stoma.