Localization of COX-2 in the male reproductive tract during sexual maturation

Prostaglandins (PGs) are shown to influence sperm motility, contractility of the smooth muscle layers surrounding the seminiferous tubules and growth of both the seminal vesicle and the ventral prostate. PGs are produced by two distinct isoforms of cyclooxygenase (COX), including constitutively expressed COX-1 and inducible COX-2. To investigate the potential role of COX-2 in male reproductive tract maturation, we evaluated its expression in rats at pre-pubertal (14 days old), peri-pubertal (21, 28 and 35 days old) and post-pubertal (62 days old) stages. COX-2 was constitutively expressed in the initial segment of the epididymis, caput epididymidis and vas deferens at all stages of maturation. Its expression was mild in 14-day-old rats but its intensity markedly increased at 28 days and remained elevated afterwards. There was no COX-2 staining in the testis, rete testis, efferent ducts or cauda epididymidis. These data suggest that COX-2 derived PGs may be involved in the pubertal development of the epididymis, but not in the more apical regions of the excurrent duct system, including the rete testis and efferent ductules.     

Changes Produced in the Male Genital Organs of Rabbits and Dogs by 2,6-cis-Diphenylhexamethylcyclo-tetrasiloxane (KABI 1774)

Abstract: The drug. 2,6-cis-diphenylhexamethylcyclotetrasiloxane, was administered daily per os to rabbits (2 mg/kg body weight in soybean oil) for 2, 5, 10, 15, 20, 25, and 30 days, and to dogs (10 mg/kg and 250 mg/kg) for 40 days. Light and electron microscope studies were made on the testis, epididymis and accessory genital glands. In rabbits, cell death was seen in the epididymis, especially in the middle caput after 2, 5 and 10 days. Longer treatment also caused marked atrophy of the epididymal duct epithelium, and some atrophy of the accessory genital glands. After 15 days, spermatozoa no longer showed the morphological maturation changes that normally take place in the caput epididymidis, and the fine structure of the epididymal epithelium suggested a return to prepuberal conditions. After 20 days, spermatozoa in the the cauda epididymidis were dead. The seminiferous tubules showed arrested spermatogenesis followed by degeneration of all spermatids and many spermatocytes between 15 and 25 days. Some ultrastructural changes of the Leydig cell cytoplasm occurred after 10 days, before spermatogenesis was disturbed. In dogs, the effect on the seminiferous epithelium varied from arrested spermatogenesis to complete degeneration of most germ cells. The interstitial cells showed atrophy, shrinkage of the nucleus, and marked loss of the specialized cytoplasmic ultrastructure. The epididymis showed some cell death and very marked epithelial atrophy. The prostate gland showed marked epithelial atrophy, with a few areas also displaying epithelial metaplasia. These observations are compatible with the concept that the cyclotetrasiloxane compound has an antigonadotropic action, but an additional direct antiandrogenic effect on the epididymis may also be involved.     

Fate of cadmium in rat renal tubules: a microinjection study

109Cd was injected into the lumen of superficial proximal or distal tubules of rat kidneys, and recovery in the pelvic urine from the ipsilateral kidney was measured. Fractional recovery of labeled inulin always exceeded 90%. About 70% of injected inorganic Cd (CdCl2) was taken up by the epithelium of proximal tubules, while more than 90% of the injected amount was recovered after distal microinjection. The proximal fractional Cd uptake of a 1:1 (molar) Cd-L-cysteine complex was 82%, but was below 60% for a 5-10:1 molar ratio of cysteine:Cd. The chelate Cd-pentetic acid was recovered in final urine nearly quantitatively after proximal or distal microinjection. Fractional uptake of 109Cd from a Cd-metallothionein (Mt) complex, following proximal microinjection, ranged between 17 (Cd-Mt 0.19 mM) and 8% (Cd-Mt 1.5 mM). It is concluded that luminal Cd uptake by the tubular epithelium depends markedly on the chemical form of Cd and, when present, occurs mostly or exclusively in proximal tubules.     

Efficacy of exogenous gonadotropins on the maintenance of spermatogenesis in pethidine treated albino rats

An attempt is made to induce the pethidine suppressed gonadal activities by the administration of exogenous gonadotropins (hCG, PMSG, hCG + PMSG). Administration of 5 IU gonadotropins either separately or in combination to the rats treated with pethidine for 30 days resulted in the significant increase in the weight of testis, diameter of testis and seminiferous tubules. Gonadotropin(s) treatment stimulated the spermatogenic activity which was inhibited by pethidine. Therefore the number of spermatogonia, spermatocytes, spermatids in the seminiferous tubules and spermatozoa in cauda epididymis is increased significantly. Decreased testicular cholesterol, increased protein content and weight of accessory sex organs indicate the rejuvenation of steroidogenesis. Combination of both the gonadotropins is more effective in bringing all these activities.     

Antispermatogenic and antifertility effects of 20,25-diazacholesterol dihydrochloride in mice

The effect of intraperitoneal administration for 28 days of 10, 20, and 30 mg/kg body weight per day of 20,25-diazacholesterol dihydrochloride (SC 12937), a hypocholesterolemic agent, on the testis of Parkes (P) strain mice was investigated. Histologically, testes in mice treated with 10 or 20 mg/kg body weight of SC 12937 showed non-uniform degenerative changes in the seminiferous tubules as both affected and normal tubules were observed in the same section; the affected tubules showed intraepithelial vacuolation, occurrence of giant cells, exfoliation of germ cells, and marginal condensation of chromatin in round spermatids. In both dosage groups, only 11-12% of the seminiferous tubules were affected, and no significant differences were found in the frequency of affected tubules between the two groups. By contrast, testes in mice treated with 30 mg/kg body weight of the drug exhibited a degenerated appearance of germ cells in all seminiferous tubules. The treatment also had adverse effects on motility, viability, morphology, and number of spermatozoa in the cauda epididymidis, and on fertility. Even 56 days after drug withdrawal, the above parameters remained markedly affected. Our results thus suggest that SC 12937 treatment causes antispermatogenic and antifertility effects in P mice and that the effects are not reversible up to 56 days after drug withdrawal. This compound may prove useful in the control of rodent populations.     

Effects of fluoride on the histoarchitecture of reproductive organs of the male mouse

The effects of sodium flouride (NaF) ingestion in two doses (10 and 20 mg/kg body weight) for 30 days on histology and histocytometry of reproductive organs of the adult male mouse were investigated. In order to study reversibility, treatment was withdrawn for one and two months. The testes, epididymides, vas deferens, prostate, and seminal vesicle were utilized for the study by standard hematoxylin-eosin staining and an ocular eye piece and micrometer scale. NaF treatment caused severe disorganization and denudation of germinal epithelial cells of seminiferous tubules with absence of sperm in the lumina. The Leydig cell and nucleus diameters were not affected. The caput epididymis showed fewer changes than the cauda. However, epithelial cell nuclear pyknosis and absence of luminal sperm were observed. A reduction in epithelial cell height, nuclear pyknosis, denudation of cells, and absence of sperm occurred in the cauda epididymis. The vas deferens epithelium showed nuclear pyknosis, clumped stereocilia, and cell debris but no sperm in the lumen and an increase in the lamina propria. The prostate and seminal vesicles were not affected by treatment. Withdrawal of treatment caused marked recovery in the histoarchitecture of these organs. The effects of NaF treatment are therefore transient and reversible.     

Evaluation of reproductive parameters in adult male Wistar rats after subchronic exposure (gavage) to benomyl

Proven-breeder 102-d-old male Wistar rats were gavaged daily with 0, 1, 5, 15, or 45 mg/kg.d benomyl. The animals were bred to untreated females after 62 d and killed after 76-79 d for evaluation of selected male reproductive end points. Minimal to moderate changes were observed in rats dosed with 45 mg/kg.d; these included decreased testis and epididymis weight, reduced cauda sperm reserves, decreased sperm production, increased numbers of decapitated spermatozoa, and increased numbers of seminiferous tubules containing multinucleated giant cells. Reproductive performance, seminal vesicle and prostate weight, sperm motility, serum luteinizing hormone, follicle-stimulating hormone, prolactin, and androgen binding protein were not affected by any of the dosages tested. Based on these end points, the no-effect level was 15 mg/kg.d.     

Effect of acute exposure to boric acid on the male reproductive system of the rat

Adult male rats were dosed orally on d 0 with 0 or 2000 mg/kg of boric acid and killed on posttreatment d 2, 14, 28, and 57, or dosed with 0, 250, 500, 1000, or 2000 mg/kg of boric acid and killed on posttreatment d 14. At d 14, atypical structures that appeared to be enlarged irregular cytoplasmic lobes of Step 19 spermatids were observed in Stage VIII seminiferous tubules of rats dosed with 1000 and 2000 mg/kg. Abnormal retention of Step 19 spermatids and residual bodies was also observed in Stage IX-XIII tubules of these rats. The retained spermatids and residual bodies were seen in both the luminal and basal regions of the epithelium. A substantial increase in the testicular sperm head count occurred in animals dosed with 2000 mg/kg. Abnormal caput epididymal sperm morphology and reduced caput epididymal sperm reserves were observed at 1000 mg/kg and higher. Serum LH, FSH, TSH, and prolactin values were not affected at any dosage. At d 28, rats dosed with 2000 mg/kg exhibited continued retention of Step 19 spermatids into Stage X, abnormal caput and cauda sperm morphology, and decreased percentages of motile cauda spermatozoa with reduced straight-line swimming velocities. By d 57 substantial recovery was apparent; some retention of Step 19 spermatids into Stage X tubules was still present in two out of six rats but the sperm parameters were comparable to controls. The study indicated that acute oral exposure to boric acid adversely affected spermiation and sperm quality in the adult male rat. At the dosages used the effects appeared reversible. The no-effect level was 500 mg/kg.     

The antagonistic effect of chlorpromazine on cadmium toxicity

Adult male rats were injected sc with cadmium chloride (CdCl(2)) in a single dose of 7 mg/kg body wt. Twenty-four hours postinjection, exposure to CdCl(2) increased the hemoglobin absorbance of the testes from 0.36 +/- 0.01 to 2.46 +/- 0.02. Pretreatment of rats with chlorpromazine (CPZ) 3 mg/kg ip either for 1 or 2 days before exposure to CdCl(2) significantly (p < 0.05) reduced the testicular damage and the hemoglobin absorbance decreased to 1.03 +/- 0.02 and 0.92 +/- 0.04, respectively. After CdCl(2) injection there was a progressive increase in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. CdCl(2) injection induced hemorrhage and a diffuse area of coagulative necrosis in liver. Pretreatment with CPZ partially protected liver from the effect of CdCl(2). Two months postinjection, exposure to CdCl(2) significantly decreased the weights of testes, epididymis, and accessory sex organs. Furthermore, CdCl(2) induced a highly significant (p < 0.01) decrease in sperm cell concentration and the percentage of mobile cells. Moreover CdCl(2) induced degenerative changes in testes, epididymis, and seminal vesicles. Pretreatment with CPZ partially protected these organs from the toxic effects of CdCl(2). It could be concluded that chlorpromazine partially antagonized the toxic effects of cadmium on liver, testes, and other male reproductive organs of rats.     

Acute toxicity of 1,2-dibromo-3-chloropropane in the F344 male rat: II. Development and repair of the renal,epididymal, testicular,and hepatic lesions

A single sc injection of 100 mg/kg 1,2-dibromo-3-chloropropane (DBCP) to adult, male F344 rats caused severe damage to the kidney, epididymis, and testis, and injury of lesser severity to the liver. The renal injury consisted of proximal tubular necrosis, severe impairment of tubular function, and increased urinary excretion of protein and several enzymes. Although function returned to normal within 5–10 days after DBCP treatment, large areas of the kidney were fibrotic and contained foci of interstitial nephritis 30 days postexposure. The testicular lesion consisted of progressive seminiferous tubular desquamation and atrophy, while epithelial cells in the caput epididymis became necrotic shortly after treatment and appeared to slough into the tubular lumen. Although a large animal to animal variation was observed, numerous seminiferous tubules were still devoid of germinal cells 30 days after DBCP treatment and epididymal sperm density remained low. DBCP caused transient increases in liver weight and the activities in serum of several enzymes associated with chemically induced hepatotoxicity and produced mild periportal hepatocellular swelling. The liver effects were relatively mild and completely reversed within 48–72 hr. These results confirm that DBCP is a nephrotoxicant and gonadotoxicant in rats and indicate that acute intoxication may cause irreversible effects. Moreover, the testicular lesion produced by a single exposure to DBCP resembles that found in humans repeatedly exposed to DBCP. The male F344 rat, therefore, appears to be an appropriate model for studying the mechanisms of infertility and other toxic effects of DBCP.     

Effects of valproic acid on fertility and reproductive organs in male rats

Crj:CD(SD)IGS rats were orally administered valproic acid at doses of 250, 500 or 1000 mg/kg/day for 4, 7 or 10 weeks. At each dose, one group of male rats was euthanized after 4-week dosage (4-week dose group) and the other two were mated with untreated females after 4 (7-week dose group) or 7 (10-week dose group) weeks of treatment with valproic acid and their fertility was evaluated. Females were euthanized on day 14-17 of gestation, and numbers of corpora lutea, implantations and live and dead fetuses were recorded. After 4, 7 or 10 weeks of treatment, males were euthanized, genital organs were weighed, the number of sperm in the cauda epididymis was counted, sperm motion analyzed, and histopathological examination of testes performed. The male rats of the 1000 mg/kg dose group died or were moribund 3 or 4 days after the start of treatment. No effects on fertility of male rats were observed up to the 500 mg/kg 10-week dose group. Treatment for 4 weeks at 500 mg/kg/day decreased epididymis weight. After 7 weeks at 500 mg/kg/day, the weights of epididymis, seminal vesicles and prostate were decreased, and the number of sperm heads per cauda epididymis and percentage of motile sperm were reduced. In the 500 mg/kg 10-week dose group, the weight of testis was decreased. On histopathological examination of the testis, degeneration of seminiferous tubules and loss or exfoliation of spermatids were observed, and the ratio of retention of step 19 spermatids in stage IX-XI was increased in the 500 mg/kg 4-, 7- and 10-week dose groups. These results suggest that analysis of sperm motion and histopathological evaluation of testes are sensitive methods for assessing toxicity of valproic acid on male reproductive organs.     

Effects of dietary selenium (SE) on morphology of testis and cauda epididymis in rats

Selenium is an essential micronutrient for animals. To determine whether its excess in diet induces morphological changes within the male reproductive system, a detailed qualitative and quantitative evaluation of the changes in the histology of the testis and cauda epididymis was undertaken in male rats. Adult male albino rats were fed 6 and 8 ppm Se in diet for 6 and 9 weeks. Each male consuming 6 ppm Se was mated with two untreated females, their offsprings were allowed to mature upto 12 weeks of age. The testes and cauda epididymes of male rats were prepared for light microscopy. Excess of dietary Se caused dose-time-dependent reduction in body weight and reproductive organ weights but increase in number of morphologically abnormal spermatozoa. Histopathological studies of the testes and cauda epididymis have revealed that Se-rich diets cause dose-time-dependent reduction in tubular diameter, epithelial height, number of spermatogenic cells and disintegration of cellular associations in the seminiferous tubules of testes along with reduction in the diameter of cauda epididymal tubules and pseudostratification of their epithelial lining. Progeny (feeding on normal diet) of paternally treated rats has shown retarded growth.     

In utero exposure to diethylstilboestrol or 4-n-nonylphenol in rats: number of sertoli cells,diameter and length of seminiferous tubules estimated by stereological methods

The effects on testis weight and histopathology were studied in 11-day-old male Wistar rats after prenatal exposure to peanut oil (control), diethylstilboestrol 30 microg/kg b.wt./day, or 4-n-nonylphenol 75 mg/kg b.wt./day from gestational day 11 to 18. Additionally, the diameter and length of seminiferous tubules, and the number of Sertoli cells were investigated with stereological methods. Such unbiased methods have not previously been applied on testis diameter and length or on Sertoli cell number of 11-day-old rats. In the control group, the mean length of the seminiferous tubule was 3.0 m+/-0.6, the mean diameter of the seminiferous tubule was 83 microm+/-6, and the mean number of Sertoli cells was 26.1x10(6)+/-4.6. No differences in testis weight, histopathology, or length or diameter of the seminiferous tubules were observed in the diethylstilboestrol and nonylphenol exposed groups when compared to the control group. In the diethylstilboestrol-treated group, a statistically significant decrease in the number of Sertoli cells was observed (P<0.01) when compared to the control group, whereas nonylphenol had no effect. The result suggests that diethylstilboestrol decreases Sertoli cell proliferation in the foetal testis and furthermore indicate that oestrogens may pose a risk to the reproductive capacity in sensitive species, including man.     

Reproductive toxicity of a single dose of 1,3-dinitrobenzene in two ages of young adult male rats

These studies evaluated the reproductive response and the possible influence of testicular maturation on the reproductive parameters, in male rats treated with 1,3-dinitrobenzene (m-DNB). Young adult male rats (75 or 105 days of age) were given a single oral dose of 0, 8, 16, 24, 32, or 48 mg/kg of m-DNB and killed at 14 days post-treatment. Mortality and neurotoxicity were observed at 48 mg/kg, but only in the older animals. Epididymis weight, testicular sperm head counts, cauda sperm reserves, and sperm morphology were affected at 16 and 24 mg/kg and higher in the older and younger animals, respectively. Testis weight and sperm motility were affected at 24 mg/kg and higher in both age groups. Histologic changes included maturation depletion of mid and late spermatids at 16 mg/kg and higher, atrophy of a few to many seminiferous tubules at 24 mg/kg and higher, and immature germ cells in the epididymis. The movement and/or mixing of luminal elements in the epididymis appeared to be influenced by severe testicular effects. In separate groups given only the 48 mg/kg dosage, fertilizing ability was lost by 5–6 weeks post-treatment and several animals failed to recover in 5 months. In the breeder males, minimal to extensive degrees of seminiferous tubule atrophy and sloughed germ cells in the epididymis were still present after 175 days. The studies indicated that the lowest dosage to produce reproductive changes was 16 mg/kg with a no-effect level of 8 mg/kg. A few animals suffered protracted or permanent reproductive damage. Since the older animals were more susceptible to both the general and the reproductive toxicity of m-DNB, the less severe reproductive changes in the younger animals cannot be attributed solely to maturational differences in the testis.     

Catalase in Testes and Epididymidis of Wistar Rats Fed Zinc Deficient Diet

Catalase activities have been evaluated in testes and caput and cauda epididymis of Wistar rats fed on zinc deficient diet for 2 and 4 weeks. The enzyme activity has been measured as chromic acetate formed by heating of dichromate (in acetic acid) in presence of H₂ O₂ with perchromic acid as an unstable intermediate. Observed non-significant increase in catalase activity in testes as well as in caput and cauda epididymis of 2 weeks experiments has been related to low levels of H₂ O₂ produced in two organs whereas significant (P<0.01/0.001) increase in catalase activity in 4-weeks experiments indicate for increased oxidative stress due to phagocytotic activity of Sertoli cells in testes and damaged spermatozoa in epididymis. Thus, zinc deficiency increases catalase activity in testes and epididymis.     

The method of sperm collection significantly influences sperm motion parameters following ethane dimethanesulphonate administration in the rat.

Sperm motion analysis following exposure to a reproductive toxicant is one means of evaluating the functional integrity of the testis and epididymis. In this study we sought to determine whether the method used to collect sperm from the proximal cauda epididymidis, where sperm are not completely mature, has a significant influence on sperm motion parameters. Two methods of collecting rat sperm for motion analysis were used: one based on an aspiration technique selected from the literature; the other, a new approach based on diffusion of sperm from the epididymal tubule. The two methods were tested for sensitivity to effects on sperm motility parameters 4 days after a single exposure to ethane dimethanesulphonate (EDS). Since EDS is known to decrease serum testosterone (T), an additional group of rats received T-filled implants just prior to dosing to determine if the decrease in serum T alone had an effect on sperm motility. The results of the study yielded strikingly different interpretations of the effect of a 65 mg/kg BW dose of EDS on the motility of sperm taken from the proximal cauda epididymidis. Sperm collected by "aspiration" showed no significant decrease in the percentage of motile or progressively motile sperm compared to vehicle-treated animals. On the contrary, sperm collected by "diffusion" showed large, significant decreases in the percentages of both motile and progressively motile sperm. This difference was due largely to lower percentages of motile and progressively motile sperm in control sperm samples collected by aspiration. Similarly, the motion parameters of sperm collected by the aspiration method were unaffected by EDS/T treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Toxicological effects of acrylamide on rat testicular gene expression profile

Toxicological effects of acrylamide on differential gene expression profile of rat testis were evaluated. Acrylamide induced morphological sperm defects, and decreased sperm concentration in cauda epididymis. Serum testosterone level and Leydig cell viability were also decreased dose-dependently, which resulted in decreased spermatogenesis. Acrylamide-induced histopathological lesions, such as formation of multinucleated giant cells and vacuolation, and numerous apoptotic cells were observed in seminiferous tubules. cDNA microarray analysis revealed that genes related to testicular-functions, apoptosis, cellular redox, cell growth, cell cycle, and nucleic acid-binding were up/down-regulated in testes isolated from acrylamide-treated group (60 mg/kg/day). Acrylamide toxicity appears to increase Leydig cell death and perturb gene expression levels, contributing to sperm defects and various abnormal histopathological lesions including apoptosis in rat testis.     

Epididymal sperm motion as a parameter of male reproductive toxicity: sperm motion, fertility, and histopathology in ethinylestradiol-treated rats.

The present study was designed to characterize the effect of ethinylestradiol (EE) on epididymal sperm motion using a computer-assisted sperm analysis system (CASA), and to elucidate the correlation between sperm motion endpoints and other measures including fertility, histopathologic, and endocrinologic endpoints. EE was orally given to adult male rats at a daily dosage of 10 mg/kg for 3 and 5 d, and at daily dosages of I and 10 mg/kg for 1, 2, 3, and 4 weeks. Changes in sperm motion were first detected after one week of treatment. Of nine sperm motion parameters, the percentage of motile sperm, velocity, and amplitude of the lateral head displacement (ALH) were decreased in the 10 mg/kg dosing group. Accompanying the decreases in those parameters, the male fertility indices in the 10 mg/kg dosing group were reduced after one week of treatment, and no males in this group could impregnate intact females after 2 weeks or more of treatment. The number of sperm heads in the cauda epididymis in the 10 mg/kg dosing group was reduced to about one-half that in the control group after one week of treatment, whereas the total number of homogenization-resistant advanced spermatids in the testis was not altered and only a slight change was detected in the number and morphology of germ cells in the testis. These results suggest that reduction in the number of epididymal sperm and in sperm motion are not secondary to testicular alteration. However, after 3 weeks of treatment, the number of sperm heads in the testis was drastically reduced with severe atrophy of the seminiferous tubules both in the 1 and 10 mg/kg dosing groups. The profiling of epididymal luminal fluid proteins indicated that two major bands that migrated with molecular weights of about 22 and 23 kDa were weakened and their density was reduced to approximately 70% of the control after 5-d and one week treatments in the 10 mg/kg dosing group. Circulating testosterone declined drastically after 3 d of treatment and remained at undetectable levels with a concomitant decline of circulating LH and FSH, suggesting that EE inhibits testosterone secretion immediately via a negative feedback system, and there follow changes in the accessory reproductive organs including the epididymis. These results indicate that EE affects epididymal spermatozoa before testicular germ cells via a testosterone deficiency, when it is administered at extremely high dosages. The reduction in the sperm motion manifested as decreases in the percentage of motile sperm, ALH, and velocity, is considered to be responsible for the onset of infertility. Sperm motion analysis could be particularly useful for detecting the toxic effects of chemicals that act through the endocrinologic system on the epididymis.     

Acute toxicity of 1,2-dibromo-3-chloropropane in the F344 male rat: I. Dose-response relationships and differences in routes of exposure

Single treatments of F344 male rats with the nematocide 1,2-dibromo-3-chloropropane (DBCP) produced acute injury to the kindney, epididymis, testis, and liver. Severity was proportional to the size of the dose administered, but the kidney was adversely affected at a lowere single dose (40 mg/kg) than was the testis or liver (80 mg/kg). Primary target cells in the kidney were proximal tubular epithelia in the outer medulla. Disturbances in renal function included impaired tubular reabsorption (e.g., glucose, fluid, and electrolyte transport) and reduced glomerular filtration. Mild, hepatocellular swelling was produced by 40 mg/kg DBCP, while the leakage of intracellular enzymes into the blood, and centrolobular hepatocellular necrosis occurred after 80 and 120 mg/kg, respectively. The acute testicular lesion was characterized by degeneration and desquamation of the caput epididymal (head of the epididymis) epithelium and by disruption of the seminiferous tubular architecture; these effects were more severe after 120 mg/kg than after 80 mg/kg. Comparisons of the acute toxicity of DBCP following repeated sc, po (by gavage), and ip administration (40 mg/kg daily for 4 days) failed to reveal qualitative differences attributable to the route of exposure. However, the severity of the renal lesion appeared comparatively greatest when treatment occurred sc. These results indicate that DBCP is a cytotoxicant for epididymal and renal proximal tubular epithelia and, since lesions were produced by repeated exposure to acutely subtoxic doses, suggest that its effects on these tissues may be cumulative.     

Adenosine triphosphatase systems in genital tract of testosterone treated male adult monkeys

Studies on the distribution of Na+, K+-dependent, Mg2+ dependent and Ca2+ dependent Adenosine Triphosphatase (ATP-ases) in the testes, epididymis, seminal vesicles and prostate glands of mature bonnet monkeys were carried out with and without Testosterone propionate (TP) treatment. Comparatively, the Ca2+ dependent ATP-ase was very active in the testes, caput and cauda epididymis and prostate of control animals. However, the Mg2+-dependent ATP-ase activity was predominant in the seminal vesicles. In all the genital tissues the Na+, K+ dependent ATP-ase exhibited low activity compared to other ATP-ase systems. On TP treatment at 1 mg/kg body wt. dose for 30 consecutive days to the second group of animals, all classes of ATP-ases drastically decreased in the testes, cauda epididymis, seminal vesicles and prostate. While in caput epididymis the Mg2+-dependent ATP-ase was stimulated, the Na+, K+-dependent ATP-ase was decreased both in the caput and corpus epididymis by the hormone treatment. The present study reveals the general inhibitory influence on the ATP-ase systems and thereby ionic transport after long term TP administration.