The abnormal development of male sex organs in the rat using a pure antiandrogen and a 5 alpha-reductase inhibitor during gestation.

The effects of a pure antiandrogen flutamide and the 5 alpha-reductase inhibitor finestaride on both prenatal differentiation of prostate and external genitalia were studied in the rat. In control male offspring the mean value of anogenital distance was 3.1 +/- 0.24 mm, and in control female was 1.2 +/- 0.10 mm. In control male newborn rats, histological sections at cranial portion of the urethra revealed prostate bud formation. Male offspring prenatally exposed to 6 mg/Kg/day of flutamide had a significant decrease in anogenital distance, but no alteration in prostate bud formation. At higher dosages of flutamide, the external genitalia were virtually feminizated and the prostatic budding was completely inhibited. In male offspring treated 'in utero' with doses of finestaride of 2, 8 and 16 mg/Kg/day, the anogenital distance became progressively reduced, but complete abolition of prostate development never occurred. However, in male offspring given finestaride at a dose of 2 mg/Kg/day concomitantly with flutamide at a dose of 6 mg/Kg/day, prostate differentiation was completely abolished.

The abnormal development of male sex organs in the rat using a pure antiandrogen and a 5 alpha-reductase inhibitor during gestation.

The effects of a pure antiandrogen flutamide and the 5 alpha-reductase inhibitor finestaride on both prenatal differentiation of prostate and external genitalia were studied in the rat. In control male offspring the mean value of anogenital distance was 3.1 +/- 0.24 mm, and in control female was 1.2 +/- 0.10 mm. In control male newborn rats, histological sections at cranial portion of the urethra revealed prostate bud formation. Male offspring prenatally exposed to 6 mg/Kg/day of flutamide had a significant decrease in anogenital distance, but no alteration in prostate bud formation. At higher dosages of flutamide, the external genitalia were virtually feminizated and the prostatic budding was completely inhibited. In male offspring treated in utero with doses of finestaride of 2, 8 and 16 mg/Kg/day, the anogenital distance became progressively reduced, but complete abolition of prostate development never occurred. However, in male offspring given finestaride at a dose of 2 mg/Kg/day concomitantly with flutamide at a dose of 6 mg/Kg/day, prostate differentiation was completely abolished.

Effects of castration, androgen replacement and flutamide treatment on the contractile function of the rat prostate.

The contractile activity of the rat prostate was registered in vivo by means of a video recording system. An increase in tone was registered in control animals after electrical stimulations were applied to hypogastric ganglion. Similar result was obtained after norepinephrine or acetylcholine administration. Such responses suffered a progressive declination in bilaterally castrated rats, although marked ultrastructural changes were not seen in the prostatic muscle cells after surgery. However, the rhythmic spontaneous activity disappeared rapidly after operation. Both, testosterone or 5 alpha-dihydrotestosterone replacement restored the normal contractile function. Flutamide treatment caused also a decrease in the responses, but they were of inferior value than those obtained after surgical castration. Neither bilateral vasectomy nor bilateral epididymectomy caused alterations in the prostatic contractile behavior.

Effects of castration, androgen replacement and flutamide treatment on the contractile function of the rat prostate.

The contractile activity of the rat prostate was registered in vivo by means of a video recording system. An increase in tone was registered in control animals after electrical stimulations were applied to hypogastric ganglion. Similar result was obtained after norepinephrine or acetylcholine administration. Such responses suffered a progressive declination in bilaterally castrated rats, although marked ultrastructural changes were not seen in the prostatic muscle cells after surgery. However, the rhythmic spontaneous activity disappeared rapidly after operation. Both, testosterone or 5 alpha-dihydrotestosterone replacement restored the normal contractile function. Flutamide treatment caused also a decrease in the responses, but they were of inferior value than those obtained after surgical castration. Neither bilateral vasectomy nor bilateral epididymectomy caused alterations in the prostatic contractile behavior.

The in vivo effects of autonomic drugs and electroejaculation on prostate gland contractility in the rat.

The effects of various autonomic drugs and electroejaculation on the contractile activity of the rat prostate were registered in vivo by means of a video recording system. The changes in the glandular tone were measured by observing the modification of distance between two superficial paralel blood vessels used as references. Norepinephrine, epinephrine, acetylcholine and electrical stimulations produced an increase in the ronus. Since terbutaline had no effect, and phentolamine prevented the effects of both norepinephrine and epinephrine but propranolol did not, it resulted that contractility of the prostate is enhanced when the alpha-adrenoceptors are stimulated, and it is not affected by the stimulation of beta-adrenoceptors. The effects of acetylcholine were blocked by atropine, indicating that they are of the muscarinic type. The excitatory response of the prostate to electroejaculation appeared to be resistant to blockade by phentolamine and atropine.

Changes in the contractile activity of the male genital tract as a consequence of vasectomy.

The contractile activity of the cauda epididymidis and vas deferens was registered in the rat under a video camera at intervals up to 180 days after vasectomy. A rhythmic peristaltic activity was detected as early as 24 hours after operation, specially in the distal cauda epididymidis. The contractions increased progressively during the first 30 days after vasectomies. Thereafter, the activity remained stabilized as far as 180 days following the surgery. The contractions were more frequent in the genital tracts without granulomas than in those with this complication. When the ductus exhibited an excessive distention their muscle walls did not show any contractility, which was not recovered even when a partial incision was made in the vas deferens to diminish the tube dilatation. Since a normal pattern of sperm transport would be necessary to achieve sperm maturation, it could be speculated that persistence of infertility after vasovasostomies in human could be related with a loss of an adequate ductal activity.

PIP: By means of a video recording system, the contractile muscle activity in the cauda peididymidis and vas deferens of male Wistar rats after vasectomy was studied over time. A rhythmic peristaltic activity was detected in the genital tracts of vasectomized rats as early as 24 hours after the procedure, with a mean frequency of 9.5 contractions/10 minutes. This activity increased progressively in the 1st 30 days after vasectomy and then stabilized as long as 180 days. By 30 days after surgery, all genital tracts exhibited sperm extravasation. The proximal ligated end of the vas deferens was the most common site for granuloma. The contractions were more frequent in genital tracts without granulomas than in those with this complication. When the ductus exhibited excessive distention, there was no contractility in the muscle walls, even when a partial incision was made in the vas deferens to reduce tubal dilatation. This suggests that extreme distention can damage the contractibility of the muscle fibers. Since the advance and return of sperm inside the tubes could facilitate the interaction of sperm with secretions participating in its maturation, the persistent infertility after vasectomy could be related to the contractile alteration that follows the excessive tubal distention. The partial reduction of the high intravasal pressure occurring during sperm extravasation relieves extreme distention of the ductal muscle, suggesting that granuloma formation may prevent damage to the contractile components and reduce the effectiveness of vasectomy.

Changes in the contractile activity of the male genital tract as a consequence of vasectomy.

The contractile activity of the cauda epididymidis and vas deferens was registered in the rat under a video camera at intervals up to 180 days after vasectomy. A rhythmic peristaltic activity was detected as early as 24 hours after operation, specially in the distal cauda epididymidis. The contractions increased progressively during the first 30 days after vasectomies. Thereafter, the activity remained stabilized as far as 180 days following the surgery. The contractions were more frequent in the genital tracts without granulomas than in those with this complication. When the ductus exhibited an excessive distention their muscle walls did not show any contractility, which was not recovered even when a partial incision was made in the vas deferens to diminish the tube dilatation. Since a normal pattern of sperm transport would be necessary to achieve sperm maturation, it could be speculated that persistence of infertility after vasovasostomies in human could be related with a loss of an adequate ductal activity.

Contractile behaviour of rat seminal vesicle after gonadectomy, testosterone replacement and cyproterone treatment.

The effects of bilateral gonadectomy, testosterone replacement and cyproterone acetate treatment on seminal vesicle contractions were studied in rats in order to contribute new data on the role of androgens in the spontaneous motility of the seminal vesicle. In gonadectomized-testosterone treated rats the glands exhibited a spontaneous rhythmic activity similar to that of entire animals. The seminal vesicles of gonadectomized as well as of cyproterone treated rats also contracted spontaneously but the contractions showed a smaller amplitude. Such decrease could be related with the well-known atrophy and reduction in the number of smooth muscle cells occurring in seminal vesicles after castration. The results reported in this paper suggest that androgens are not required for the normal spontaneous activity of seminal vesicles.

Effects of autonomic drugs on contractions of rat seminal vesicles in vivo.

Various autonomic drugs were placed on the peritoneal covering of the seminal vesicles of anaesthetized rats. Adrenaline (which stimulates the alpha-, beta 1- and beta 2-adrenoceptors) and phenylephrine (an alpha-stimulating agent) produced a sudden increase in tonus and in the amplitude and frequency of contractions. Phentolamine (an alpha-blocker) prevented these effects, whereas propranolol (a beta 1- and beta 2-blocker) did not. Phentolamine also abolished the seminal vesicle response to electrical stimulations. Terbutaline (a beta 2-stimulating agent) did not affect the spontaneous activity. There were no differences between the effects of terbutaline alone and those of terbutaline in the presence of propranolol. Moreover, propranolol did not block the contractile response of the gland to adrenaline or to electrical stimulation. These results indicate that alpha-adrenergic receptors are present in the muscle cell membrane of the rat seminal vesicle. The effects of acetylcholine were similar to those produced by adrenaline or phenylephrine although of smaller magnitude. Atropine prevented the effects of acetylcholine, indicating that they are of the muscarinic type.

In vivo recording of contractile activity of pelvic urethra and seminal vesicle in rats. Effects of electrical stimulations and neurohypophysial hormones.

The spontaneous contractility of the pelvic urethra and seminal vesicles in the rat was recorded in vivo and the effects of the electrical stimulation as well as the neurohypophysial hormones on it were studied. The mean amplitude of pelvic urethra contractions was 3.2 +/- 0.9 cm H2O and the mean frequency was 4.1 +/- 0.8 contractions/min. The seminal vesicles contractions exhibited a mean amplitude of 1.6 +/- 0.7 cm H2O and a mean frequency of 2.6 +/- 0.8 contractions/min. Each electrical stimulation produced a sudden and vigorous contraction in pelvic urethra as well as in seminal vesicles. Oxytocin and vasopressin did not change neither the amplitude nor the frequency in the spontaneous activity of these organs.

On the problem of the phagocytic capacity of Sertoli cells. Electron microscopic study in the rat.

To study the real phagocytic capacity of Sertoli cells the following experiments were carried out: carbon colloidal solution or thorium dioxide of particle size 0.01--0.03 micrometer as 2% solution were injected in rat testes at a speed of 50 microliter per minute by means of a infusion pump. The site of injection was made either in the intertubular species under the albuginea or in the lumen of seminiferous tubules using glass 120 micrometer-gauge needles connected to the pump syringe. 30 to 240 minutes after the injection the tissues were fixed by perfusion of 2% glutaraldehyde and embedded for EM. It was observed: 1) particles injected into the intertubular species were not able to pass through the tubular wall and were either trapped by the connective tissue macrophages or drained by the lymphatic vessels; 2) intraluminal particles were not phagocyted by the Sertoli cells and remained in the lumen. The behavior of the Sertoli cells did not match that of phagocytes since they did not show their devouring capacity for the inert particles. These results are consistent with the interpretation that the current disposal of either debris by Sertoli cells depends on autophagic dissolution rather than n macrophagic capacity.

Effect of chronic treatment with prostaglandin E2 on male rat fertility.

Adult male rats were treated with prostaglandin E2 (100 microgram/100 g body wt) during 60 days. Neither morphological alterations in genital organs nor modification in epididymal contractility were observed. Nevertheless, a significant diminution of fertility was registered. This was recovered after 30 days following the cessation of treatment. Since sperm maturation occurs in the epididymis, it is postulated that the decrease of fertility in our experiments was due to an incomplete maturation of germinal cells, induced by a reduction in the time taken by spermatozoa in passing through the duct.

Contractile behaviour of rat epididymis after sympathectomy produced by the administration of guanethidine.

The effect of guanethidine (a sympatholytic agent) on epididymal contractions was studied in rats, in order to contribute new data on the role of both the adrenergic and cholinergic nerves in the spontaneous motility of the epididymis and also during ejaculation. The first type of activity was increased when adrenergic innervation was damaged, but the amplitude and frequency of contractions reached normal values approximately 3 hours after beginning the records. Since spermatozoa were eliminated after electroejaculation, the second type of contractions was not affected either. As the epididymis and vas deferens were congested with spermatozoa, it is possible to assume that guanethidine caused a functional obstruction in a distal segment of the genital tract. The increase of spontaneous activity could be the response of the epididymal muscle to overcome this obstruction and, therefore, to cause the elimination of spermatozoa into the urethra, which normally occurs in absence of ejaculations. Finally, no pregnancies occurred among female rats mated with treated males, at least up to 150 days after ending treatment.

Effects of prostaglandins and indomethacin on rat epididymal responses to norepinephrine and acetylcholine.

Prostaglandins E2 and F2alpha tromethamine salt caused an increase in amplitude and frequency of rat epididymal contractions. Moreover, they caused a significant potentiation of contractile responses of epididymal smooth muscle to stimulation by norepinephrine or acetylcholine. Indomethacin treatment caused no changes in the spontaneous motility, and this inhibitor of prostaglandins synthesis decreased the responses of epididymis to norepinephrine or acetylcholine. Spontaneous motility of epididymis is possible in the presence of smaller amounts of endogenous prostaglandins, and sudden contraction occurring during ejaculation, induced by sympathetic and parasympathetic nerves stimulation, could be influenced or modulated by prostaglandins.

Effects of cyproterone acetate on spontaneous contractility of the rat epididymis.

The spontaneous contractility of the rat epididymis was recorded in vivo and the effects of cyproterone acetate were studied. At 7 days after cyproterone acetate daily administration the records of the epididymal contractility did not show significant differences from the records obtained in control animals. On the contrary, in animals injected during 11 days the amplitude and frequency of epididymal contractions showed a significant decrease, and this activity completely ceased at 14 days of treatment.

The 'in vivo' effects of oxytocin and vasopressin on spontaneous contractility of the rat epididymis.

The spontaneous contractility of the epididymis in the rat was recorded in vivo and the effects of the neurohypophyseal hormones were studied. Oxytocin (50 muU and 500 muU/100 g body weight) produced a progressive increase in tonus together with an increase in amplitude and frequency of the contractions. Vasopressin (100 muU and 1000 muU/100 g body weight) showed similar effects. No differences were apparent at the doses studied.

Effects of autonomic drugs on epididymal contractions.

The spontaneous contractility of rat epididymis was recorded in vivo and the effects of various autonomic drugs were studied. Norepinephrine, epinephrine, and orciprenaline produced a sudden increase in tonus and in the size and frequency of epididymal contractions. Phentolamine (an alpha-blocker agent) inhibited the effects of norepinephrine. On the other hand, alprenolol (a beta-blocker agent) inhibited the effects of orciprenaline but did not block the effects of norepinephrine. In addition, phentolamine and alprenolol decreased the spontaneous activity of the epididymis. Acetylcholine produced effects similar to those of norepinephrine. These effects were blocked by atropine. The results described would indicate the presence of the two receptors, alpha and beta, and that both are mediators of stimulatory effects.