Expression Of Progesterone Receptors In The Human Fetal Genital Tubercle During Sex Specific Morphogenesis: Implications For The Endocrine Disruptor Hypothesis In The Etiology Of Hypospadias

Purpose

In the two recently published studies, it was reported that the progesterone receptors (PR) and consequently progesterone may be involved in normal or anomalous development of mice external genitalia. However the literature lacks data regarding the existence of PRs in the human fetal genital tubercles.

Material and Methods

The study was performed on 16 normal humal fetal specimens (8 male and 8 female) at 13 to 19 weeks of gestation. The external genitalia of each specimen was carefully dissected immediately after abortion, fixed with formalin, embedded in paraffin and serially sectioned at 5 microns. Immunocytochemistry was assessed on selected sections with an antibody raised against the progesterone receptor. The staining intensity and distribution were recorded.

Results

Progesterone receptor expression was positive on all sections. The staining intensity was highest in the distal urethra followed by a moderate staining in glans, cavernosal bodies and skin. Prostatic urethra, bladder neck and bladder sections revealed negative staining signal. No difference was noted between male and female genital tubercles in terms of the tissue distribution and staining intensity of progesterone receptor expression.

Conclusions

Progesterone receptors are expressed in developing human genital tubercles, suggesting a direct role of progesterone in normal human genital tubercle patterning. The existence of positive signal in the distal urethra but not in the proximal urethra implies a potential sensitivity of the distal urethra to the effects of estrogenic or progestogenic endocrine disruptors during fetal period, which may be an important finding in understanding the molecular basis of hypospadias.

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