# Reduced Expression of Oestrogen Receptors Alpha and Beta in the Prepuce and Urethral Plate of Hypospadias Patients: A Clinical Study

## TL;DR

This study finds reduced oestrogen receptor expression in foreskin and urethral plate tissues of hypospadias patients compared to normal controls.

## Contribution

The study identifies distinct patterns of ERα and ERβ expression in hypospadias tissues, linking oestrogen receptor dysfunction to penile development.

## Key findings

- ERα expression is weak in proximal hypospadias foreskin and urethral plate tissues.
- ERβ is strongly expressed in the stratum basale and spinosum of foreskin tissues.
- Oestrogen receptors play a significant role in penile and urethral development.

## Abstract

Introduction: The human skin is an important oestrogen-responsive organ containing the oestrogen receptors ERα and ERβ. Penile foreskin may have similar properties; therefore, typifying the expression and cellular location of oestrogen receptors ERα and ERβ in hypospadiac and normal foreskin can expand our knowledge of the aetiology of hypospadias.

Materials and methods: We prospectively analysed foreskin and longitudinally excised tissue of the urethral plate of 52 male patients undergoing hypospadias repair. Sixteen male patients undergoing elective circumcision were used as controls. Based on the ectopic location of the urethral meatus, hypospadias was classified as distal (group A), mid (group B), and proximal (group C). Healthy controls were included in group D. Oestrogen receptors' location and expression were characterised by immunohistochemical analysis of foreskin and urethral plate tissues.

Results: ERα expression in foreskin was intermediate in control and distal and mid-penile hypospadias and weak in proximal hypospadias. Urethral plate ERα expression was intermediate in distal hypospadias and weak in mid-penile and proximal hypospadias. ERβ immunoreactivity was strong in the stratum basale and stratum spinosum, whereas ERα was localised to the stratum basale of the foreskin.

Conclusions: These data demonstrate a significant role of oestrogen and oestrogen receptors in normal penile foreskin and urethral plate development.