Estrogen receptor-alpha is required by the supporting somatic cells for spermatogenesis

The gene for estrogen receptor-alpha (ER alpha) was disrupted ill embryonic stem cells by homologous recombination and these cells were used to genera te mice with a targeted mutation in the ER alpha gene (alpha ERKO mice). It was found that males homozygous for the mutation are infertile, indicating that estrogen signaling through this nuclear hormone receptor is required for male reproductive function. Although spermatogenesis arrears normal in juvenile and young adult alpha ERKO mice, the sperm produced are unable to fertilize eggs in vitro. To determine whether ER alpha is required by somat ic or germ cells in the male reproductive tract, we transplanted germ cells from homozygous mutant (ER alpha (-/-)) males to the testes of wild-type ( ER alpha (+/+)) males depleted of germ cells by busulfan treatment. The rec ipients ('surrogate fathers') sired offspring heterozygous for the mutation (ER alpha ('/-) and carrying the coat-color marker of the infertile donor males. This indicated that ER alpha (-/-) germ cells an able to produce spe rm competent to fertilize when they are supported by ER alpha (+/+). somati c cells. When ER alpha (+/-) offspring produced by germ cell transplantatio n were mated to produce ER alpha (-/-) males, these mice were found to have the same phenotype as originally reported for alpha ERKO males. These stud ies showed that male germ cells do not require ER alpha for regulation of t heir own genes for development and Function, and strongly imply that somati c cells of the male reproductive tract require ER alpha to support the prod uction of sperm that are capable of fertilization. (C) 2001 Elsevier Scienc e Ireland Ltd. All rights reserved.