The ureter arises from the mesonephric or Wolffian duct (WD) and, depending on the progressive absorption of the WD into the urogenital sinus, the ureter and WD become separated [123]. The absorption process was recently revealed in photographs of serial embryonic sections [4]. The initial absorption results in a pair of wing-like posterior protrusions of the future bladder. In contrast to the ureteral orifice, which remains at the tip of the protrusion, the WD appears to move medially and inferiorly. In adult males, however, the mesonephric duct-derived vas deferens opens to the urethra at the colliculus seminalis 3 or more centimeters below the ureteral openings. Similar to vaginal descent [5], the descent of the WD or vas deferens in embryos and/or fetuses should occur along the developing bladder and urethra.

At present, the process of descent of the WD or vas deferens, as determined by distance below the bladder relative to weeks of gestation, remains unclear. Rather than differentiating of urogenital sinus into the bladder and urethra, the later development of the prostate may separate the WD opening from the bladder neck. The urogenital sinus- or WD-derived structure in the bladder trigone has been immunohistochemically examined in animal models [67]. Briefly, WD-derived epithelium undergoes apoptosis and is replaced in the trigone by sinus-derived epithelium. However, the timing and intermediate morphologies during descent remain to be determined in human embryos and fetuses. Therefore, descent was morphometrically evaluated by assessing sagittal sections of 15 specimens at approximately 6–8 and 10–12 weeks of gestation, and topographical changes along the transverse axis were determined by examining horizontal sections of 20 specimens at 6–8 and 9–10 weeks of gestation.

The study was performed in accordance with the provisions of the Declaration of Helsinki 1995 (as revised in Edinburgh 2000). The embryonic sections were from the large collection kept at the Embryology Institute, Universidad Complutense, Madrid. The specimens in the collection were products of miscarriages and ectopic pregnancies managed at the Department of Obstetrics at the university. In our previous study about vaginal descent [5], in the collection, female specimens were listed up according to a morphology containing a single thick, central dauct (Műllerian duct and its derivative) with a pair of thin dicts (WD remnants). Therefore, we easily chose male specimens for the present study.

The descent of the WD or vas deferens was strictly estimated by examining serial sagittal sections of nine embryos of crown-rump length (CRL) 21–35 mm (gestational age, 6–8 weeks) and of six fetuses of CRL 50–70 mm (gestational age 10–12 weeks). Topographical changes along the transverse axis were assessed in detail by examining horizontal sections of 12 embryos of CRL 15–30 mm (gestational age, 6–8 weeks) and of eight fetuses of CRL 35–45 mm (gestational age, 9–10 weeks). All sections were stained with hematoxylin and eosin, orange-G or silver stain. The study protocol was approved by the university ethics committee (No. B08/374).

This study demonstrated intermediate morphologies during the descent of WD opening at the colliculus seminalis. Due to the drastic upward growth of the smooth muscle-containing bladder, the descent of the WD opening became evident at 10–12 weeks. Growth of the urogenital sinus was largely directed along an oblique supero-inferior axis toward the umbilicus: the width of the bladder was limited to 0.8 mm in contrast to its 5 mm length at 10 weeks. Therefore, fewer developmental changes in the urogenital sinus than expected were observed in the horizontal sections. Similarly, the epithelium of the future bladder was identical to the epithelium of the future urethra. Conversely, differentiation of urogenital sinus into the bladder and urethra did not start from their transverse shapes but from the muscles associated with them. Thus, the smooth muscles developing in the bladder wall as well as the striated muscles along the urethra seemed to be essentially important for the site-dependent differentiation of the sinus. Attachment of the WD to the future urethra seemed to induce this difference in muscles. Smooth muscle differentiation in the upper half of the urogenital sinus near the urachus was likely to start earliest in the body. Thus, more strictly, the WD seemed to suppress any positive role of the urogenital sinus or urachus, favoring smooth muscle differentiation. These morphological changes were followed by development of the prostate and, later, by a further, much greater descent of the WD opening. These suggested processes differ markedly from vaginal descent, in which the distal end of the Műllerian duct appears to attach to and slide actively downward along the urethral wall [5].

Our recent study showed individual morphologic variations at the joining of the WD and ureter among similar-sized specimens at 5–6 weeks [4]. In this study, we observed that the urogenital sinus had a reversed Y-shape, the arms of which appeared to be derived from the WDs. Actually, all of the specimens in this study had bilateral wing-like protrusions to receive the WD and ureter. Our previous study hypothesized that, when absorption of the WD reached the distal terminal of the ureter, the wing-like parts would enlarge posteriorly for further involvement of the duct with little or no incorporation of the distal ureter [4]. Absorption of the ureter into the sinus or bladder was unlikely along such a long distance (>0.5 mm). In fact, the distance from the ureteral opening to the upper margin of the pubis was almost stable (0.1–0.2 mm) at 6–12 weeks despite the drastic increase in body size. The increased distance between the ureteral opening and WD opening seemed to be largely dependent on the de novo production of the bladder wall, especially by smooth muscles before birth, as well as by an increased size of the prostate after birth.

The bladder appeared to grow toward the umbilicus possibly due to a mechanical stress from the umbilical cord [8]. Growth or elongation of the urachus in the umbilical cord seemed to accelerate smooth muscle development in the bladder wall. The urachus also contained many smooth muscles. Combinations of abnormalities in the urachus and abnormalities of the bladder and urethra, such as undescended bladder, sagittal septum of the bladder and urethral stenosis, have been reported [9]. Indeed, defects in the lower abdominal wall, as well as abnormal traction of the umbilical cord, seen in omphalocele, were most likely to have a deleterious effect on normal development from the urogenital sinus to the bladder [1011]. Recent advances in ultrasound techniques revealed urachus defects in fetuses in utero [1213]. However, abnormalities in the vas deferens and/or colliculus seminalis, even if present, would be found after puberty. A slight abnormality or accident in the umbilical cord or umbilicus may be associated with small changes in the topographical anatomy of the bladder, urethra and vas deferens. These slight changes may result in marked disturbances in male sexual function.

Overall, in contrast to the ureteral opening, which remains almost in its initial position in the urogenital sinus or bladder, the WD orifice at the colliculus seminalis was found to descend due to muscle differentiation and development in the bladder and along the urethra.