Immunolocalization of androgen receptor and estrogen receptors α and β in human fetal testis and epididymis

Purpose: Expression and cellular localization of the androgen receptor (AR) and estrogen receptor (ER) isoforms were determined using antibodies specific to these receptors and to specific cell types. Materials and Methods: Gonads and genitourinary structures were removed from 5 human male fetuses 7 to 22 weeks of gestational age. Sections were stained with antibodies to AR, ERα and ERβ, P450 scc and smooth muscle actin. Results: AR was present in undifferentiated gonadal cells, peritubular myoid cells and in some Leydig and stromal cells at 7 weeks of gestation. The number of AR positive peritubular myoid cells remained constant through 22 weeks of gestation but the number of AR positive stromal cells continued to increase through 22 weeks. ERα was apparent by 12 weeks of gestation with perinuclear staining of Leydig cells, peaked at 16 weeks and then diminished. ERβ was first observed at 7 weeks in undifferentiated gonadal cells. By 12 weeks of gestation ERβ was apparent in germ cells, PTMC and Leydig cells. In the epididymis AR was expressed in the epithelium and stroma of the efferent ductules and the ductus epididymis by 7 weeks of gestation with increased expression by 12 weeks. A similar pattern of staining was observed for ERβ. By contrast, staining of ERα was observed only in the epithelium of the epididymis from 7 weeks of gestation onward with no apparent ERα staining in the tail of the epididymis. Conclusions: These findings are compatible with the well-known roles of androgen signaling in sexual differentiation and spermatogenesis in humans. The role of estrogens in the developing human testis and epididymis remains unknown.