Christopher J. Calvano

Unilateral suprainguinal ectopic scrotum: The role of the gubernaculum in the formation of an ectopic scrotum

A rare case of ectopic scrotum is described together with a review of the literature and a discussion of the embryological role of the gubernaculum in the formation and location of normal and ectopic scrota. We identified 16 reported cases of a suprainguinal ectopic scrotum, 4 cases of a femoral ectopic scrotum, 26 cases of penoscrotal transposition, and 19 cases of a perineal (accessory) scrotum. Although the gubernaculum is a prerequisite for the ultimate location of both the testis and scrotum, its role is complicated by the subsequent differential growth of the labioscrotal folds in which the gubernaculum is stabilized. If this interaction is disturbed, the result may be a suprainguinal ectopia, penoscrotal transposition or a perineal scrotum. A femoral ectopic scrotum, unlike the above, is the result of an aberrant gubernacular stabilization. While the etiology of these malformations is likely to be multifactorial, the existence of an inbred strain of rats characterized by a high incidence of an ectopic scrotum suggests a genetic component to this anomaly.

Experimental study of umbilical cord length as a marker of fetal alcohol syndrome.

Umbilical cord length has long been investigated as a potential marker of intrauterine events that may place the neonate at risk for future adverse developmental sequelae. Experimentally, significantly shortened cords have been reported in association with prenatal exposure to common drugs of abuse. This study in rats reports the time course of effects on umbilical cord length of a daily maternal ethanol gavage (3,200 mg/kg) from gestational day 6 through termination of pregnancy at either day 17, 18, 19, or 20. A total of 786 fetuses derived from 60 litters were examined. Control fetuses demonstrated a linear increase in umbilical cord length and body weight gain during late gestation, findings that support previous studies. The body weights of the ethanol-exposed fetuses were reduced significantly on all gestational days examined, indicating intrauterine growth retardation, a characteristic of fetal alcohol syndrome. Similarly, acute fetal akinesia as well as long-term sequelae stemming from impaired neurological development would result from the elevated blood ethanol levels achieved in this study. The umbilical cords of ethanol-exposed fetuses were significantly shorter on gestational days 19 and 20 in comparison to their controls, while cord lengths on days 17 and 18 were not shortened significantly. A stretch hypothesis has been proposed suggesting that the degree of fetal activity is the main determinant of umbilical cord length. In rats, there is a physiologic diminution of the volume of amniotic fluid (oligohydramnios) in late gestation (day 19 to term), which restricts fetal movements but does not appear to alter the linear relationships between gestational age and cord length in controls, thus arguing against the stretch hypothesis. However, cord lengths in the ethanol-exposed fetuses plateaued in late gestation, suggesting possible adherence to a stretch hypothesis. This dichotomy is discussed emphasizing fetal growth and activity as well as intrauterine space.

XX Sex Reversal: Molecular Analysis of the SRY/ZFY Regions

PURPOSE The mammalian sex determining gene, sex region Y chromosome (SRY), is now firmly established as the testis determining locus. The SRY locus is close to the short arm Y terminus and just distal to zinc finger Y region (ZFY), a locus previously thought to be involved in testicular differentiation and the male phenotype. We report on XX sex reversal, a rare sex chromosomal disorder in humans. MATERIALS AND METHODS Routine amniocentesis revealed an XX fetal karyotype, although at birth the neonate was phenotypically male. Radiographic evaluation showed a normal male urethra and the absence of any female internal genitalia. Subsequent molecular analysis with polymerase chain reaction amplified sequences of the SRY and ZFY loci were positive. RESULTS This case is the fourth in our series of XX sex reversed male individuals and to our knowledge the first to be diagnosed perinatally. In all cases the SRY and ZFY loci are present, presumably on the paternal X chromosome, as well as a Klinefelter phenotype. These sex reversing translocations are thought to be due to an unequal meiotic recombination of the distal X and Y short arms during male gametogenesis. The tendency for XY translocations to break between the SRY and ZFY loci was not seen in these apparent microtranslocation cases. CONCLUSIONS These 4 cases demonstrate the usefulness of molecular followup of clinically perplexing sexual discordance. We conclude that SRY and ZFY polymerase chain reaction amplification studies should be performed when sexual discrepancies are noted on prenatal ultrasound and karyotype analysis.

The incidence of renal anomalies at full term in fetal rats is synergistically increased by estradiol (but not testosterone) supplementation on day 18 of alcoholic gestation

BACKGROUND/PURPOSE Fetal alcohol syndrome is characterized by facial dysmorphology, mental and growth retardation, and somatic anomalies including hydronephrosis. The authors sought to determine the influence of exogenous testosterone or estradiol on the incidence of hydronephrosis in a rodent model of fetal alcohol syndrome (FAS). METHODS Pregnant rats were fed a liquid diet containing 35% ethanol-derived calories from gestation day 6 through 15, with exogenous testosterone or estradiol supplementation on day 18. On day 20, fetal kidneys were examined for evidence of hydronephrosis, and fetal serum estradiol concentrations were determined by radioimmunoassay. RESULTS Maternal estrogen supplementation resulted in very high fetal serum estradiol levels that were not additionally increased by alcoholism. Despite this fact, the expression of renal malformations was highest in the alcoholic, estradiol-supplemented offspring. Additionally, the rate of renal malformations was significantly higher in the estrogen-supplemented alcoholic group than in the strictly estradiol animals, yet the fetal serum estradiol concentrations did not differ between the two groups. CONCLUSIONS This suggests that ethanol may act synergistically with estradiol to increase the rate of renal anomalies including hydronephrosis. Such damage may persist via a suppression of normal testosterone-stimulated renal growth and development. FAS includes significant renal anomalies characterized by hydronephrosis in both animal models and affected children. Although the long-term functional sequelae of hydronephrosis and reflux are well known, the progression of renal disease in FAS children remains to be documented.

Mouse paracentric inversion In(3)55Rk mutates the urate oxidase gene

The paracentric inversion In(3)55Rk on mouse Chromosome 3 (Chr 3) was induced by cesium irradiation. Genetic crosses indicate the proximal breakpoint cosegregates with D3Mit324 and D3Mit92; the distal breakpoint cosegregates with D3Mit127, D3Mit160, and D3Mit200. Giemsa-banded chromosomes show the inversion spans ∼80% of Chr 3. The proximal breakpoint occurs within band 3A2, not 3B as reported previously; the distal breakpoint occurs within band 3H3. Mice homozygous for the inversion exhibit nephropathy indicative of uricase deficiency. Southern blot analyses of urate oxidase, Uox, show two RFLPs of genomic mutant DNA: an EcoRI site between exons 4–8 and a BamHI site 3′ to exon 6. Mutant cDNA fails to amplify downstream of base 844 at the 3′ end of exon 7. FISH analysis of chromosomes from inversion heterozygotes, using a cosmid clone containing genomic wild-type DNA for Uox exons 2–4, shows that a 5′ segment of the mutated Uox allele on the inverted chromosome has been transposed from the distal breakpoint region to the proximal breakpoint region. Clinical, histopathological, and Northern analyses indicate that our radiation-induced mutation, uoxIn, is a putative null.

Laparoscopic In Utero Surgery

Fetal surgery is an experimental venture still in its infancy, yet advancements have progressed at an exponential rate in the past 20 years since the publication of the first clinical studies of operative decompression of the obstructed fetal urinary tract. Key obstacles have included anesthesia, tocolysis, and access, which are critically intertwined. Modified laparoscopic techniques have shown promise in animal models of reducing uteroplacental disruption while facilitating definitive fetal repair and minimizing maternal risk. In fact, congenital diaphragmatic hernia is now managed clinically by fetoendoscopic tracheal clipping. It is likely that a select population of fetuses with obstructive uropathies will benefit from in utero decompression of the developing urinary system. Past efforts have included open fetal surgical creation of vesicostomy and percutaneously placed vesicoamniotic stents. Unfortunately, these techniques have been limited in their success. Recently, minimally invasive techniques have been employed to examine the fetal bladder in utero for the purpose of ablating obstructive causes such as posterior urethral valves. Although the ideal candidate for intervention is often difficult to define, current research seeks to generate amnioscopic strategies for safe fetal urinary diversion in those select fetuses that have salvageable renal and pulmonary function. These strategies include vesicoamniotic stents that are placed and suture-secured with the use of simultaneous ultrasonographic and amnioscopic imaging. Creation of in utero laser vesicostomy is also feasible with simultaneous ultrasound and amnioscopy. To avoid unnecessary poor outcomes, the development of fetal surgical technique must keep pace with studies that seek accurate prognostic factors by defining the pathophysiology of obstructive uropathies.