Objective To determine the development of the human penis, and hence t
he cause of congenital anomalies, using an immunohistochemical analysi
s of fetal penile ontogeny. Materials and methods In 25 human fetal pe
nile specimens (gestational age 8 to 23 weeks) various tissues were lo
calized immunohistochemically using stains for alpha-actin (smooth mus
cle), cytokeratin 8 and 14 (epithelium) and protein gene-product (PGP)
9.5 (neurons). Results Nerves were identified in the penis with anti-
PGP in specimens of all ages, prominent dorsally at the 11 and 1 o'clo
ck positions but also extending around the tunica to the junction of t
he corpus spongiosum and corpora cavernosa, suggesting that these stru
ctures may be injured in procedures which straighten the penis. The ne
rves continued into the glans on the dorsal aspect, suggesting that gl
ans reduction in feminizing genitoplasties should be performed on the
ventral aspect. Smooth muscle was first noted at 10 weeks' gestation,
with epithelial differentiation occurring in the earliest specimens st
udied (8 weeks' gestation). With time, smooth muscle density was highe
st in the corpus spongiosum, especially between it and the corpora cav
ernosa. Smooth muscle also developed close to the urethral epithelium.
The tunica albuginea showed consistent variations in thickness, with
the mid-dorsal 12 o'clock position being the thickest, followed by the
5 and 7 o'clock periurethral positions. Conclusion A better knowledge
of penile development and of the relationship of the nerves to the co
rpora cavernosa is useful in the strategic design of penile straighten
ing procedures and feminizing genitoplasties.