A comparison of prostatic development in xenografts of human fetal prostate and human female fetal proximal urethra grown in dihydrotestosterone-treated hosts

Abstract

The goal of this paper is to explore the ability of the human female urogenital sinus immediately below the bladder (proximal urethra) to undergo prostatic development in response to dihydrotestosterone (DHT). To establish this idea, xenografts of human fetal female proximal urethra were grown in castrated nude mouse hosts receiving a subcutaneous DHT pellet. To verify the prostatic nature of the resultant glands, DHT-treated human fetal female urethral xenografts were compared with human fetal prostatic xenografts (derived from male specimens) grown in untreated and DHT-treated castrated mouse hosts and human fetal female proximal urethral xenografts grown in untreated castrated hosts. The resultant glands observed in DHT-treated human fetal female proximal urethral xenografts expressed 3 prostate-specific markers, NKX3.1, prostate specific antigen and prostatic acid phosphatase as well as the androgen receptor. Glands induced by DHT exhibited a protein expression profile of additional immunohistochemical markers (seven keratins, RUNX1, ESR2, TP63 and FOXA1) consistent with the unique spatial pattern of these proteins in prostatic ducts. Xenografts of human fetal female proximal urethra grown in DHT-treated hosts also expressed one of the salient features of prostatic development, namely androgen responsiveness. The experimental induction of prostatic differentiation from human fetal female proximal urethra makes possible future in-depth analysis of the molecular pathways directly involved in initiation of human prostatic development and subsequent epithelial differentiation, and more important whether the molecular pathways involved in human prostatic development are similar/identical versus different from that in murine prostatic development.

Keywords: Androgen receptor; Development; Female prostate; NKX3.1; Urethra.