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

The estrogen receptor-alpha knockout (ER alpha KO, ER alpha(-/-)) mice were generated via the Cre-loxP system by mating floxed ER alpha mice with beta-actin (ACTB)-Cre mice. The impact of ER alpha gene deletion in the male reproductive system was investigated. The ACTB-Cre/ER alpha(-/-) male mice are infertile and have lost 90% of epididymal sperm when compared with wild-type mice. Serum testosterone levels in ACTB-Cre/ER alpha(-/-) male mice are 2-fold elevated. The ACTB-Cre/ER alpha(-/-) 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/ER alpha(-/-) mice display reduced branching morphogenesis. Loss of ER alpha 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/ER alpha(-/-) prostates. Collectively, these results suggest that ER alpha 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. (Endocrinology 150: 251-259, 2009)