Effects of sialoadenectomy and epidermal growth factor on testicular function of sexually mature male mice.

The effect of sialoadenectomy (Sx) and epidermal growth factor (EGF) administration on testicular function was investigated in 8-week old C3H mice. Animals were divided initially into three groups: sham operated controls, Sx, and Sx + EGF treated (100 micrograms./kg./day subcutaneously for 28 days). Sialoadenectomy completely depleted the circulating levels of EGF and reduced body weight and reproductive organ weights. However, kidney weight was not affected. Quantitative analysis of spermatogenesis showed a decrease in preleptotene and pachytene spermatocytes and round spermatids, which resulted in a decrease in sperm counts. Sperm motility and fertility were also significantly decreased. Endocrinologic studies showed a 2- and 6-fold elevation in intratesticular and serum levels of testosterone and a decrease in luteinizing hormone (LH) levels. Follicle stimulating hormone levels were not altered. Administration of EGF to the Sx animals maintained reproductive organ weights, spermatogenesis and levels of LH and testosterone closer to control values; however, sperm motility was not maintained at control value. That sialoadenectomy resulted in a decline in androgen-dependent parameters, in spite of an elevation in testosterone levels, and EGF maintained them closer to the control value suggested that EGF may modulate androgen action. A comparison was therefore carried out between the effects of Sx and administration of flutamide (F), an androgen receptor blocker. Animals were subjected to Sx, F treatment (100 mg./kg./day subcutaneously for 28 days), Sx + F, or Sx + F + EGF. The effects of Sx and F treatment on organ weights, sperm counts and sperm motility were more or less similar. As expected, flutamide treatment increased LH and FSH levels, and testosterone levels were normal. The Sx + F animals showed no further decrease in organ weights, sperm count and motility. Treatment with Sx + F increased intratesticular and serum levels of testosterone by 2- and 10-fold. Circulating levels of LH and FSH were the same as in the flutamide-treated group. Administration of EGF to Sx + F maintained all these parameters, except sperm motility, closer to the control value. These results suggest that EGF either bypasses flutamide effects and acts directly or that EGF modulates androgen action at one or more steps in the signal transduction pathway in the male reproductive organs.

Long-term followup of bladder mucosa graft for male urethral reconstruction.

Autologous bladder mucosa was used as a free graft for complex urethral reconstruction in 95 male patients, ranging in age from 1 to 21 years. Primary indications for surgery include previous failed hypospadias repair in 68 cases, primary hypospadias in 11, bladder exstrophy/epispadias complex in 10 and others in 6. Patients were divided into 3 groups based on the configuration of the bladder mucosa replacement. Group 1 (37 patients) underwent complete urethral replacement to the tip of the glans. Group 2 (16 patients) underwent placement of a bladder mucosa onlay patch graft. Group 3 (42 patients) underwent a combined repair using tubularized bladder mucosa proximally and either a pedicled preputial tube (6), free preputial or penile skin tube (13), local glandular skin flaps (15), or intact glandular urethra or tubularized urethral plate (8) distally to avoid a terminal segment of bladder mucosa. All patients were followed for a mean of 3.4 years (range 6 months to 8 years). An overall good functional and cosmetic result was eventually achieved in 81 patients (85%). However, 63 patients (66%) required between 1 and 9 (mean 2.7) additional procedures to treat complications before achieving a good result. The most common complications were meatal stenosis and/or prolapse. Meatal problems were significantly more common in group 1 (68%) than in those who underwent a patch or combined procedure (12 and 36%, respectively). Although bladder mucosa provides an excellent and readily available material for urethral substitution in these challenging cases, the urologist should be aware of the significant incidence of postoperative problems and their management. The high incidence of meatal problems suggests that bladder mucosa should not be incorporated as a circumferential terminal urethral segment.

Effects of subchronic treatment with cis-platinum on testicular function, fertility, pregnancy outcome, and progeny.

Cis-platinum-based chemotherapy is known to impair spermatogenesis, but the effects of paternal cis-platinum treatment on the progeny are unknown. To study this effect, sexually mature male Sprague-Dawley rats were administered intraperitoneal injections of saline or cis-platinum (0.5 mg/kg per day) for 9 weeks. Every week, one set of control and treated animals was mated with females in proestrus. Nineteen days later, the females were subjected to laparotomy, and the numbers of corpora lutea, resorptions, and normal and abnormal fetuses were noted. In conjunction, the effects of treatment on the hypothalamo-pituitary-gonadal axis of the treated males were evaluated. Cis-platinum-treated animals failed to grow; the weights of the reproductive organs and the sperm counts declined from week 2 onward, and sperm motility was reduced throughout the testing period. Circulating and intratesticular levels of testosterone declined from week 3 of treatment and follicle-stimulating hormone levels were not affected. Serum levels of luteinizing hormone declined from week 3 and were not detectable from week 6 onward. However, the pituitary response to gonadotropin-releasing hormone was intact in all treated groups. There was no significant decrease in fertility, but a prominent increase in pre- and postimplantation losses of fetuses after cis-platinum treatment was observed. There was also a decrease in the male-to-female ratio of the offspring. A small but significant number of malformed and growth-retarded fetuses was also found among the offspring of cis-platinum-treated males. These results suggest that subchronic treatment with low doses of cis-platinum may affect progeny; such effects are seen in addition to the apparent alteration in a number of measures of reproductive function of treated males.

Short term effects of cis-platinum on male reproduction, fertility and pregnancy outcome.

In order to find out the short term effects of cis-platinum treatment on reproductive function of the treated male rats and their progeny, sexually mature male Sprague-Dawley rats were given a single intra-peritoneal injection of either saline or cis-platinum (2, 4, 8 mg./kg.body wt.). One week following the treatment, the animals were mated with proestrus females of proven fertility. The females were scored positive or negative depending upon whether or not spermatozoa were seen in the vaginal smear after mating. However, all the females were watched until day 18, and on day 19, the females that became pregnant were subjected to laparotomy, and the number of corpora lutea, implantation sites and fetuses were counted. The fetuses were weighted and observed for the presence of any morphological abnormalities. Significant pre-implantation loss was seen in the treated groups. The weights of the fetuses were also significantly lower than those from the control group. Analysis of the effects of cis-platinum on the reproductive system of treated males revealed that cis-platinum reduced the reproductive organ weights, sperm counts, sperm motility, fertility and the levels of testosterone, LH and FSH. These results suggest that cis-platinum has a profound deleterious effect on the reproductive system and on the fertility potential of the treated male rats.

Microanatomy of retia mirabilia of bowhead whale foramen magnum and mandibular foramen.

The morphology of vessels of the cervical rete mirabile near the region of the foramen magnum of the bowhead whale, Balaena mysticetus, as well as of retial vessels of the mandibular foramen was studied by light and transmission electron microscopy. A comparison of arterial and venous components of the mandibular rete revealed considerable arterial branching and arteriovenous anastomoses. Although the small arteries of bowhead retia contained the same layers found in nonretial arteries, several distinctive morphologic features were evident. These included wide separation by collagenous connective tissue and small size of individual smooth muscle cells of the tunica media. These myocytes also contained considerable perinuclear glycogen and communicated minimally with adjacent myocytes by small foot-like cytoplasmic appendages as well as branching of basement membranes. Ganglia-like neural plexuses were observed within the tunica media of arterial retia. Endothelial cells lining the intima demonstrated loose peripheral edges which frequently projected into the vessel lumen, and these cells rested upon a subjacent layer of reticular fibers. It is known for some species that the retial supply to the brain in whales largely supplants an internal carotid arterial supply and that the spinal cord is supplied by retia. The physiologic role of the bowhead mandibular retia remains unknown. The retia mirabilia of cetaceans are considered as one of the morphologic adaptations which modulate hemodynamics during diving and resurfacing. The morphologic features of these vessels in the bowhead whale, as revealed by electron microscopy, appear to reflect the capability to respond in a slow but sustained manner to diving, and the large glycogen deposits may help sustain vascular myocyte metabolism during prolonged submersion.

Changes in neutrophil surface protein composition accompany phagocytosis.

Phagocytosis is a critical host defense mechanism of neutrophils. In this study, membrane protein changes occurring during phagocytosis were studied in human neutrophils using surface radiolabeling before or after phagocytosis of various target particles. Cells were labeled at the cell surface using lactoperoxidase-catalyzed iodination or neuraminidase-galactose oxidase-NaB3H4, galactose oxidase-NaB3H4, or periodate-NaB3H4 techniques. Such studies are complicated by the fact that these techniques identify many surface proteins on the phagocyte, and labeling after phagocytosis occurs often results in radiolabeling proteins of the target particle, thus making changes in cell-surface proteins more difficult to detect. Immunoprecipitation with monoclonal antibody AHN-1, which reacts with a carbohydrate present on several human neutrophil surface proteins and inhibits phagocytosis, eliminated interference caused by radiolabeled proteins of the target particle and simplified analysis by restricting the study to a limited number of proteins. AHN-1 immunoprecipitated less radiolabeled protein from neutrophils labeled after phagocytosis of particles opsonized with IgG or complement than from cells labeled before phagocytosis. Isolation of phagocytic vesicles containing opsonized emulsified paraffin oil demonstrated that three proteins of mol wt 105,000, 140,000, and 170,000 recognized by AHN-1 were internalized in the phagocytic vesicle during phagocytosis.