Spermatogenic Cells Do Not Require Estrogen Receptor-α for Development or Function

Abstract

Estrogen receptors alpha (ERα) and beta (ERβ) are ligand-dependent transcription factors and members of the nuclear hormone receptor superfamily encoded by separate genes. Male mice homozygous for a mutation in the gene encoding ERα are infertile. To determine whether germ cells or somatic cells require ERα, germ cells were transplanted from donor males homozygous for the mutation (ERα^−/−) to testes of wild-type (ERα^+/+) recipient mice depleted of germ cells. The recipients served as “surrogate fathers” for the infertile ERα^−/− males. When mated to wild-type females, the recipients sired offspring heterozygous for the mutation (ER^+/−) and carrying the coat-color marker of the ERα^−/− donor mice. These studies show that male germ cells do not require ERα for development or to function in fertilization, and imply that male ERα^−/− mice are infertile due to disruption of estrogen action within somatic cells of the male reproductive system.