The Effect of Intrauterine Vascular Compromise on Further Development of Corpus Spongiosum and Urethra

Abstract

An in-utero experimental study was performed to evaluate the effects of intrauterine vascular compromise on further development of corpus spongiosum and male urethra. Thirty time-mated pregnant New Zealand white rabbits on their twenty-third day of gestation were used. Deterioration of the blood supply of the corpus spongiosum and urethra was attempted by electrocauterizing the perineum adjacent to the root of the phallus without damaging the corpus spongiosum and urethra, under the operating microscope. A bipolar cautery was carried out using a specially designed forceps having 100 microns interspaced fixed tips. Five experimental and seven control live male litters were delivered at term by Cesarean sections. Their anogenital regions were examined histopathologically. While the corpus spongiosum extended as long as the corpus cavernosum to the tip of phallus in control litters, the corpus spongiosum ended under the skin in one of the experimental group and in the other four was shorter than the corpus cavernosum. In the latter group, no histopathological evidence of tissue destruction which might be related to electrocauterization, was found. Similar to the pathogenesis encountered in intestinal atresia, a vascular insult which might occur even after the completion of organogenesis, may affect the fate of the corpus spongiosum and urethra. Localized ischemia resulting from local vascular insults may explain, at least in theory, the pathogenesis of some congenital anomalies of corpus spongiosum and urethra such as hypospadias.

Maternal Smoking, Alcohol, and Caffeine Exposures and Risk of Hypospadias

“…Another potential mechanism to consider is the vasoactive effects of the studied exposures. Localized ischemia has been proposed to contribute to hypospadias based on experimental studies and case reports of the co‐occurrence of hypospadias and transverse limb defects among infants with alpha‐thalassemia (Kizilcan et al, ; Abuelo et al, ). However, under this proposition, we would predict these exposures to be associated with increased hypospadias risk.…”

Homozygous alpha-thalassemia associated with hypospadias in three survivors

“…The failure of the shift could lead to tissue hypoxia, which potentially may affect organogenesis of the external genitalia during this period, i.e., hypospadias. Animal studies demonstrated that interruption of blood supply to the corpus spongiosum and urethra may also result in shortening of the corpus spongiosum [Kizilcan et al, 1994]. In addition, a vasoconstrictive effect by in utero exposure to cocaine has been known to increase the occurrence of hypospadias in humans [Battin et al, 1995].…”

Limb defects and congenital anomalies of the genitalia in an infant with homozygous α-thalassemia

“…The mechanism for the abnormal sexual differentiation in homozygous ␣-thalassemia may be vascular compromise and tissue ischemia. Intrauterine localized ischemia of the corpus spongiosum and urethra in experimental animals can cause hypospadias [Kizilcan et al, 1994]. Interestingly, there is a high incidence of genital anomalies in males with the X-linked ␣-thalassemia mental retardation (ATR-X) syndrome [McPherson et al, 1995], including hypospadias, ambiguous genitalia, and female gender assignment.…”