Androgenic regulation of ventral epithelial bud number and pattern in mouse urogenital sinus

Abstract

The ventral urogenital sinus (UGS) of control male mice has two rows of 3-4 prostatic buds at birth, but how androgens regulate ventral bud (VB) number and patterning is unclear. VBs in both sexes appeared to be a mixture of prostatic and urethral buds. UGSs from Tfm male and antiandrogen (flutamide)-exposed mice had small VBs, suggesting that initiation of some VBs is androgen independent. Tfm male mice are widely considered completely androgen insensitive yet their UGSs were 5a-dihydrotestosterone (DHT)-responsive. VBs (6-8) were generally distributed bimodally on the left-right axis at both minimal and normal male androgen signaling. Yet control females and DHT-exposed Tfm males had 13-14 VBs, whose leftright distribution was fairly uniform. These results suggest that VB number and distribution respond biphasically as androgen signaling increases from minimal, and that androgens regulate bud specification. Complete VB agenesis by the selective budding inhibitor 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) required high androgen signaling. Developmental Dynamics 239:373-385,

An illustrated anatomical ontology of the developing mouse lower urogenital tract

“…The ontology uses ventral epithelial bud in favour of prostate bud for the female mouse. Whereas these buds might go on to form Skene's glands in females, no lineage tracing is available to confirm this and, even in males, not all ventral buds go on to form prostate glands (Allgeier et al, 2010).…”

“…5; supplementary material). Several studies describing early murine prostate development (Allgeier et al, 2010(Allgeier et al, , 2009Cook et al, 2007) have instructed modifications to the ontology. Numerous prostate buds develop from the PLUR epithelium in distinct locations (Fig.…”

“…5A-D). Number, size, morphology, location and patterning of the different prostate regions have been described (Allgeier et al, 2010(Allgeier et al, , 2009Lin et al, 2003;Timms et al, 1994). Bud formation is complete by E18.5 (Lin et al, 2003); however, extensive branching morphogenesis does not begin until after birth.…”

“…5; supplementary material). Ventral urethral gland buds develop at the male bladder-urethra junction in the same location as ventral prostate buds, but at early stages these are indistinguishable, as both express the early prostatic marker Nkx3-1 (Allgeier et al, 2010). Consequently, it is difficult to definitively identify any ventral budding structure in the developing male, although there is evidence that Edar and Wnt10b mRNA staining intensity can separate prostatic gland buds (high expression) from urethral gland buds (low to non-detectable expression; Keil et al, 2012).…”

“…Consequently, it is difficult to definitively identify any ventral budding structure in the developing male, although there is evidence that Edar and Wnt10b mRNA staining intensity can separate prostatic gland buds (high expression) from urethral gland buds (low to non-detectable expression; Keil et al, 2012). However, the ontology now includes the indefinite term, ventral epithelial bud, first introduced by Allgeier et al (2010) (Fig. 5A-H).…”