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The embryological development of the urogenital system, derived from the intermediate mesoderm, proceeds through 2 closely linked processes: Urinary System Development: Arising from the nephrogenic cord. Reproductive System Development: Arising from the gonadal ridge. Proper formation of both systems relies on the coordinated activity of multiple genes and hormones. Disruptions or mutations at any point in this developmental cascade can result in duplicated, absent, or malformed structures. A thorough understanding of urogenital embryology is therefore essential for accurate diagnosis and effective management of a wide range of congenital and acquired conditions.

Urinary System Wilms tumor (nephroblastoma) arises in the kidney due to a mutation in the WT1 gene on chromosome 11p13. The hypothesis is that persistent cells of the metanephric mesenchyme/blastema are precursors of 40% of Wilms tumor cases.[16] Wilms tumor is 1 component of WAGR syndrome caused by a microdeletion of WT1 and PAX6, which also features aniridia, genitourinary anomalies, and intellectual disability. Common genitourinary anomalies associated with WAGR syndrome include cryptorchidism, failure of at least 1 testis to descend, and hypospadias, an incomplete fusion of the urethral folds, resulting in an opening on the ventral aspect of the proximal penis in males. In females, it may present as streak ovaries, a hypoplastic uterus, or a septate vagina. Hypospadias commonly presents with chordee, involving the shortening and curving of the ventral penis. Wilms tumor is also a feature of several other conditions, including Beckwith-Wiedemann syndrome, Bloom syndrome, Denys-Drash syndrome, and Li-Fraumeni syndrome.[17] Autosomal recessive polycystic kidney disease (ARPKD) presents with fluid-filled cysts in the collecting ducts, leading to renal failure in childhood. In contrast, autosomal dominant polycystic kidney disease (ADPKD) features cysts in any part of the nephron and renal failure in adulthood. 85% of cases of ADPKD result from mutations in the PKD1 gene, and the remaining 15% result from mutations in the PKD2 gene.[18] Mutations in the GDNF-RET signaling pathway are implicated in the formation of a multicystic dysplastic kidney, in which multiple cysts are present and separated by parenchyma; when present bilaterally, it can cause impaired renal function since the collecting ducts within the nephrons fail to develop. Oligohydramnios results from impaired renal function and is associated with conditions such as multicystic kidney disease, bilateral renal agenesis, and renal dysplasia. Too little amniotic fluid causes the fatal Potter sequence, resulting in a fetus with craniofacial abnormalities (cleft lip, flattened face, low-set ears, recessed chin), pulmonary hypoplasia, and clubbed feet, although a child with unilateral renal agenesis can survive via compensatory hypertrophy of the functioning kidney.[19] Urinary issues associated with unilateral renal agenesis include ureteropelvic junction obstruction and vesicoureteral reflux (VUR).

Oligohydramnios results from impaired renal function and is associated with conditions such as multicystic kidney disease, bilateral renal agenesis, and renal dysplasia. Too little amniotic fluid causes the fatal Potter sequence, resulting in a fetus with craniofacial abnormalities (cleft lip, flattened face, low-set ears, recessed chin), pulmonary hypoplasia, and clubbed feet, although a child with unilateral renal agenesis can survive via compensatory hypertrophy of the functioning kidney.[19] Urinary issues associated with unilateral renal agenesis include ureteropelvic junction obstruction and vesicoureteral reflux (VUR). If the kidneys cannot ascend from the pelvis to their normal lumbar position, a pelvic kidney near the common iliac artery or a horseshoe kidney with fused lower poles may be present. The root of the inferior mesenteric artery is responsible for preventing proper ascent of the kidneys, which is commonly observed in Edwards syndrome (trisomy 18) and Turner syndrome.[20] The bladder exstrophy-epispadias-cloacal exstrophy complex is a constellation of ventral wall defects resulting from a developmental abnormality that occurs 4 to 5 weeks after conception. Bladder exstrophy exists concomitantly with epispadias, a failure of the lateral body wall folds to close in the midline, leaving the urethral meatus on the dorsum of the penis. Cloacal malformations result from the failure of anorectal and urogenital channels to separate during weeks 6 to 7 of gestation and result in a single perineal opening.[2] The diagnosis is made clinically during a newborn examination, but can present as a hydrocolpos on prenatal ultrasound or MRI. Imaging is warranted, as up to 90% of patients with a cloaca also have a urologic anomaly such as renal agenesis, horseshoe kidney, hydronephrosis, or vesicoureteral reflux.[21] A patent urachus is the persistence of the embryological connection between the dome of the bladder and the umbilicus, resulting from failure of the allantois to break down. Urine can drain from the umbilicus if there is a urachal fistula present from the persistence of the lumen of the intraembryonic portion of the allantois, causing delayed cord stump healing and edema around the umbilicus of a newborn.

A patent urachus is the persistence of the embryological connection between the dome of the bladder and the umbilicus, resulting from failure of the allantois to break down. Urine can drain from the umbilicus if there is a urachal fistula present from the persistence of the lumen of the intraembryonic portion of the allantois, causing delayed cord stump healing and edema around the umbilicus of a newborn. Several other urachal anomalies exist, including a urachal cyst (when a local remnant of the urachus persists), an umbilical-urachal sinus (resulting from failure of the umbilical end of the urachus to obliterate), and a vesicourachal diverticulum (caused by incomplete obliteration of the urachus on the bladder side).[4] Additionally, an ectopic ureter can develop if the ureteric bud undergoes abnormal migration during its insertion into the bladder. Genital System There are many steps during urogenital formation from which anomalies can arise. Failure of the paramesonephric ducts to fuse can occur at any point along the normal fusion pathway. It can result in uterine malformation, such as uterus arcuatus, a concavity at the uterine fundus due to failure of the fused midline segments to degenerate, and uterus didelphys, a complete duplication of the uterus from complete lack of fusion.[15] Uterus bicornis is a uterine anomaly in which the uterus has 2 horns entering a common vagina as a result of only a partial fusion of the paramesonephric ducts. Failure of the sinovaginal bulbs to develop results in vaginal atresia, while the failure of them to fuse results in the presence of a double vagina. A hydrocele is the buildup of fluid around the testicle due to a remnant of tunica vaginalis, present in males as a painless scrotal swelling, and can be transilluminated. The appendix testis is a vestigial remnant of the Müllerian duct located at the anterior-superior pole of the testis, and the Gartner’s duct, epoophoron, and paraoophoron are the remnants of the Wolffian duct in females. A congenital indirect inguinal hernia results from the failure of the connection between the abdominal cavity and the processus vaginalis to close, allowing loops of the bowel to descend into the scrotum.

The appendix testis is a vestigial remnant of the Müllerian duct located at the anterior-superior pole of the testis, and the Gartner’s duct, epoophoron, and paraoophoron are the remnants of the Wolffian duct in females. A congenital indirect inguinal hernia results from the failure of the connection between the abdominal cavity and the processus vaginalis to close, allowing loops of the bowel to descend into the scrotum. The most common cause of ambiguous genitalia is congenital adrenal hyperplasia, most frequently due to 21-hydroxylase deficiency (required for cortisol synthesis) caused by mutations or deletions in CYP21A, accounting for 90% of cases.[22][23] 17a-hydroxylase deficiency can also cause congenital adrenal hyperplasia, though less frequently, resulting in normal female internal and external anatomy at birth but primary amenorrhea and/or failure of secondary sex characteristics at puberty.[24] In males, small genitalia, undescended testes, or other lack of virilization at puberty may be the first sign.[25] In androgen insensitivity syndrome (AIS), receptors are unresponsive to androgens and ineffective in inducing differentiation of the male genitalia.[26] An XY male has phenotypically female genitalia, though Müllerian inhibiting substance (MIS) is present, causing the uterine tubes and uterus to be absent.[26] A micropenis, described as 2.5 standard deviations below the mean penis length when stretched, results from insufficient androgen stimulation or a defect in the HPG axis.[27] Inhibition or deficiency of the enzyme 5α-reductase results in the inability to convert testosterone to dihydrotestosterone, resulting in underdeveloped, albeit external male genitalia.[28] Lastly, XY female gonadal dysgenesis (Swyer syndrome) results from point mutations or deletions of the SRY gene. It presents in females as a lack of menstruation and/or secondary sex characteristics at puberty.[29][30]