Gubernacular development in Müllerian inhibiting substance receptor-deficient mice.

OBJECTIVE: To determine, in mice with disrupted Müllerian inhibiting substance (MIS) receptor genes, whether MIS affects gubernacular development; MIS causes Müllerian duct regression and is proposed to be involved in the first stage of testicular descent, because gubernacular development is abnormal in humans with persistent Müllerian duct syndrome. MATERIALS AND METHODS: Ten wild-type, 11 heterozygotic and 12 homozygotic mice for MIS receptor mutations were killed at 17.5 or 18.5 days after conception or at birth, to provide serial sagittal sections of the pelvis. The amount of cremaster muscle, mitotic bodies in the gubernacular bulb, and gubernacular size were quantified by computer analysis (four mice/group). RESULTS: Müllerian ducts were present in the homozygous mutants, partially present in the heterozygotes and absent in the wild-type controls. All mice had descended testes. The cremaster muscle was significantly less developed in homozygous mutants than in wild-type controls (P < 0.001) and heterozygotes (P < 0.01) at birth. The mitotic index between the gubernacula of all groups was indistinguishable. There was no statistical difference in gubernacular area amongst the groups. Poor cremaster muscle development in homozygous mutants gave the muscle a loose mesenchymal appearance. CONCLUSIONS: Although there was an observable effect on cremaster muscle development in these mutant mice, gubernacular development and testicular descent were otherwise normal, and thus there must be other reasons for the observed differences in humans with persistent Müllerian duct syndrome.

Early development of the gubernaculum and cremaster sac in estrogen receptor knockout mice.

AIM exogenous estrogen causes gubernacular atrophy and cryptorchidism in fetal rodents. Mice with an estrogen receptor-alpha (ERalpha) disrupted gene mutation (alphaERKO) were studied to determine whether ablation of endogenous estrogen action, through ERalpha, had an effect on gubernacular development. Serial sagittal sections were made of the pelvis in fetal and day 7 postnatal wild-type and alphaERKO mice with the estrogen receptor-alpha "knockout" gene mutation. Wild-type (n = 24), heterozygote (n = 13) and alphaERKO mice (n = 12) were sacrificed at 16, 17 and 18 days fetal life and at 7 days postnatally. The size of the gubernaculum, cremaster muscle, cremaster sac, and the width of the sac at both ends in day 7 mice were quantitated by computer analysis. Visually and statistically the ERKO mice could not be separated from the wild-type mice during fetal life. At day 7 postnatally, a thicker cremaster sac was noted morphologically, and also a statistically significant difference was seen in the width of the cremaster sac at the sac's tip. Sac area, cremaster muscle area and the width of the sac at the sac's end did not differ significantly. Overall there is minimal phenotypic change observed in the alphaERKO mouse compared to wild-type at the early developmental stages investigated. However, at postnatal day 7, there is a difference in the width of the cremasteric sac tip. This suggests that the effect of ERalpha, and thus signaling on the developing gubernaculum, occurs late in development. Alternatively, an action from the recently discovered ERbeta may be involved. Exploration of a betaERKO and the double knock-out alphaERKO/betaERKO mouse should be informative in evaluating the effect of endogenous estrogens in gubernacular development.

Intracranial cavernous angioma.

Cavernous angiomas are a rare but important clinical entity because of their potential curability. Three patients who had intracranial cavernous angiomas confirmed at surgery are presented. Preoperative recognition is greatly aided by a tendency to calcify, as identified both by skull films and more sensitively by computed tomography. A well demarcated collection of rounded densities of CT scanning, showing mild contrast enhancement and no significant mass effect, should suggest the possibility of cavernous angioma. Conventional angiography characteristically reveals a hypovascular appearance without abnormal arterial feeding vessels. On films of high technical quality, a subtle vascular stain, possibly associated with a few large draining veins, may be detected. There is usually no mass effect unless there has been a previous episode of hemorrhage. Cavernous angiomas may manifest a pronounced increase in activity on radionuclide brain scanning.

Familial "doughnut" lesions of the skull. A benign, hereditary dysplasia.

Multiple calvarial doughnut lesions present a dramatic roentgenographic picture. The scant literature indicates that they are benign, asymptomatic, and of obscure etiology. Three additional examples of this rare entity have been identified all in the same family and are presented. The implication of a familial relationship with regard to develpmental pathogenesis is discussed. Histology is nonspecific but is felt to be consistent with hyperostosis.