Seminal Epithelium Research Articles

Environmental Effects Of Monosodium Glutamate On (NF-κB) Levels In The Male Reproductive System Of Rats

Monosodium glutamate (MSG) has been identified as a food additive that Adversely affects MSG use on the reproductive efficiency by several mechanisms, this study was carried out to determine its role in stimulating the immune response in the reproductive system by estimating levels of NF-κB in serum and of its expression in reproductive organs. Thirty sex males rats were used in this study each included 12 male rats. Male rats A and B are receiving 60 and 120 mg/kg for 28 days respectively male rats of the control group were left without treatment for the period of the experiment. The levels of Nuclear factor-kappa NF-κB in serum and tissue fluid of testes and epididymis were measured. histological changes in addition to detection NF-κB expression were studying in testes and epididymis. Results of the present study recorded the toxic effect of MSG as it caused an elevation in the levels of NF-κB in serum, testicular, and epididymis tissue fluid. histological alternation in the reproductive organs was observed to represent detachment and vacuolation of the seminal epithelium, degeneration of spermatogenesis edema in a lumen in testicular tissues. Epididymal sections appeared to sever necrosis, degeneration in the epithelial layer and stereocilia, and the lumen of the epididymis. Also there was an increasing density of NFκB protein immunoreactivity in both testis and epididymis.

Comparative Study of the Restoring Effect of Metformin, Gonadotropin, and Allosteric Agonist of Luteinizing Hormone Receptor on Spermatogenesis in Male Rats with Streptozotocin-Induced Type 2 Diabetes Mellitus.

We compared the effectiveness of human chorionic gonadotropin (hCG; 5 days, 20 IU/rat/day), allosteric luteinizing hormone receptor agonist TP04 (5 days, 20 mg/kg/day), and metformin (28 days, 120 mg/kg/day) in restoring spermatogenesis in male rats with type 2 diabetes mellitus. hCG and TP04 increased the levels of testosterone and expression of the steroidogenic protein StAR, the number of spermatogenic cells, thickness of the seminal epithelium, and the number and motility of mature sperm that were reduced in diabetic rats, though they did not reduce the number of defective spermatozoa. Metformin had a weak effect on steroidogenesis, but was not inferior to luteinizing hormone receptor agonist by its restorative effect on spermatogenesis and also reduced the number of defective forms of spermatozoa. Thus, the spermatogenesis-restoring effect of metformin and luteinizing hormone receptor agonist in type 2 diabetes mellitus are comparable, despite different mechanisms of action.

Usefulness of GATA-3 as a marker of seminal epithelium in prostate biopsies

ObjectivesThe incidental presence of seminal vesicle epithelium in prostate needle biopsies is generally recognizable through routine microscopy. However, it can sometimes be erroneously interpreted as malignant due to its architectural and cytological characteristics, and immunohistochemistry can be useful for correctly identifying the seminal epithelium. Our objective was to analyze the potential usefulness of GATA-3 as a marker of seminal epithelium. Material and methodsThrough immunohistochemistry with a monoclonal anti-GATA-3 antibody (clone L50-823), we studied seminal vesicle sections from 20 prostatectomy specimens, 12 prostate needle biopsies that contained seminal vesicle tissue and 68 prostate biopsies without seminal vesicle epithelium, 36 of which showed adenocarcinoma. ResultsStaining for GATA-3 was intense in the 20 seminal vesicles of the prostatectomy specimens and in the 12 prostate needle biopsies that contained seminal epithelium. In the 60 biopsies without a seminal vesicle, GATA-3 was positive in the prostate basal cells and even in the secretory cells (57 cases), although with less intensity in 55 of the cases. One of the 36 prostatic adenocarcinomas tested positive for GATA-3. ConclusionsThe intense immunohistochemical expression of GATA-3 in the seminal vesicle epithelium can help identify it in prostate biopsies. This marker is also positive in the basal cells of healthy prostates and, with less intensity, in the secretory cells. Positivity, weak or moderate, is observed on rare occasions in prostatic adenocarcinomas.

Utilidad de GATA-3 como marcador de epitelio seminal en las biopsias de próstata

ObjectivesThe incidental presence of seminal vesicle epithelium in prostate needle biopsies is generally recognisable through routine microscopy. However, the biopsy can sometimes be erroneously interpreted as malignant due to its architectural and cytological characteristics, and immunohistochemistry can be useful for correctly identifying the biopsy. Our objective was to analyse the potential usefulness of GATA-3 as a marker of seminal epithelium. Material and methodsThrough immunohistochemistry with a monoclonal anti-GATA-3 antibody (clone L50-823), we studied seminal vesicle sections from 20 prostatectomy specimens, 12 prostate needle biopsies that contained seminal vesicle tissue and 68 prostate biopsies without seminal vesicle epithelium, 36 of which showed adenocarcinoma. ResultsStaining for GATA-3 was intense in the 20 seminal vesicles of the prostatectomy specimens and in the 12 prostate needle biopsies that contained seminal epithelium. In the 60 biopsies without a seminal vesicle, GATA-3 was positive in the prostate basal cells and even in the secretory cells (57 cases), although with less intensity in 55 of the cases. One of the 36 prostatic adenocarcinomas tested positive for GATA-3. ConclusionsThe intense immunohistochemical expression of GATA-3 in the seminal vesicle epithelium can help identify the epithelium in prostate biopsies. This marker is also positive in the basal cells of healthy prostates and, with less intensity, in the secretory cells. Positivity, weak or moderate, is observed on rare occasions in prostatic adenocarcinomas.

Seminal epithelium in prostate biopsy can mimic malignant and premalignant prostatic lesions

ObjectivesIn most prostate biopsies, the seminal epithelium is easily recognized because it meets characteristic histological criteria. However, some biopsies can mimic malignant or premalignant prostatic lesions. The aims of this study were to analyze the histological appearance of the biopsies that mimic adenocarcinomas or preneoplastic prostatic lesions, discuss the differential diagnosis and determine the frequency of seminal epithelia in prostate biopsies. MethodsWe consecutively reviewed 500 prostate puncture biopsies obtained using the sextant method and selected those cases in which we observed seminal vesicle or ejaculatory duct epithelium. In the biopsies in which the seminal epithelium resembled malignant or premalignant lesions, immunohistochemical studies were conducted that included prostate-specific antigen and MUC6. The most important clinical data were recorded. ResultsThirty-six (7.2%) biopsies showed seminal epithelium, and 7 of them (1.4%) resembled various prostate lesions, including high-grade prostatic intraepithelial neoplasia, atypical acinar proliferations, adenocarcinomas with papillary patterns and poorly differentiated carcinoma. The seminal epithelium resembled prostate lesions when the lipofuscin deposit, the perinuclear vacuoles or the nuclear pseudoinclusions were inconspicuous or missing. Five of the 7 biopsies showed mild to moderate cellular atypia with small and hyperchromatic nuclei, and only 2 showed cellular pleomorphism. The patients were alive and asymptomatic after an average of 6 years of progression. ConclusionsThe seminal epithelium resembles prostatic intraepithelial neoplasia, atypical acinar proliferations and various types of prostatic adenocarcinomas in approximately 1.4% of prostate biopsies.

El epitelio seminal en biopsia prostática puede semejar lesiones prostáticas malignas y premalignas

ObjectivesIn most prostate biopsies, the seminal epithelium is easily recognised because it meets characteristic histological criteria. However, some biopsies can mimic malignant or premalignant prostatic lesions. The aims of this study were to analyse the histological appearance of the biopsies that mimic adenocarcinomas or preneoplastic prostatic lesions, discuss the differential diagnosis and determine the frequency of seminal epithelia in prostate biopsies. MethodsWe consecutively reviewed 500 prostate puncture biopsies obtained using the sextant method and selected those cases in which we observed seminal vesicle or ejaculatory duct epithelium. In the biopsies in which the seminal epithelium resembled malignant or premalignant lesions, immunohistochemical studies were conducted that included prostate-specific antigen and MUC6. The most important clinical data were recorded. ResultsThirty-six (7.2%) biopsies showed seminal epithelium, and 7 of them (1.4%) resembled various prostate lesions, including high-grade prostatic intraepithelial neoplasia, atypical acinar proliferations, adenocarcinomas with papillary patterns and poorly differentiated carcinoma. The seminal epithelium resembled prostate lesions when the lipofuscin deposit, the perinuclear vacuoles or the nuclear pseudoinclusions were inconspicuous or missing. Five of the 7 biopsies showed mild to moderate cellular atypia with small and hyperchromatic nuclei, and only 2 showed cellular pleomorphism. The patients were alive and asymptomatic after an average of 6 years of progression. ConclusionsThe seminal epithelium resembles prostatic intraepithelial neoplasia, atypical acinar proliferations and various types of prostatic adenocarcinomas in approximately 1.4% of prostate biopsies.

Sexual behavior attenuates the effects of chronic stress in body weight, testes, sexual accessory glands, and plasma testosterone in male rats

The aim of this study was to evaluate whether continuous sexual behavior could attenuate the effects of chronic stress on spermatogenesis, sexual glands, plasma testosterone and corticosterone in sexually experienced male rats. Rats were exposed to stress by immersion in cold water (ICW) daily for 20 or 50 consecutive days. Plasma testosterone and corticosterone, masculine sexual behavior, as well as the number of offspring, the epithelial area of seminiferous, prostatic and seminal glands were assessed. In stressed males, body and testicular weights decreased, male sexual behavior was disrupted, and adrenal weights increased. In males stressed for 50days, prostate and seminal glands had lower weights compared with controls. Prostate and seminal epithelial areas also decreased in these males. Seminiferous tubules in testes from rats stressed for 20 or 50days showed several degenerative signs, such as vacuoles in the basal epithelium, with picnotic indicia; moderate to severe exfoliation of degenerative germinal cells in the tubule lumen was also observed. In males stressed for 50days a significant decrease in seminiferous epithelial area was observed from stages I–VIII, regardless of copulation. The litters from females that copulated with males stressed for 50days decreased significantly. Chronic stress caused increase in plasma levels of corticosterone, which were higher in males stressed for 20days than in males stressed for 50days. Testosterone decreased in stressed males and it was lower in males stressed for 50days. In stressed males allowed to copulate, body and testicular weights were similar to controls. Adrenal, seminal glands, and prostate weights, as well as epithelial areas of males stressed for 50days allowed to copulate were also similar to controls. Corticosterone was lower than in males stressed for 50days, but still higher than in controls. Testosterone in males stressed for 50days and allowed to copulate was higher than in stressed males not allowed to copulate and control males without copulation, but still lower than in control copulating males. These results show that chronic stress causes germ cell loss in testes and a decrease in prostate and seminal epithelium, possibly as a result of testosterone decrease, affecting fertility. Continuous copulation can attenuate the effects of stress on testosterone levels and on the epithelial area in male sexual glands, but not on the seminiferous epithelium after 50days of stress.

Modulatory Role of Kolaviron in Phenytoin-Induced Hepatic and Testicular Dysfunctions in Wistar Rats

ABSTRACTPhenytoin, an anticonvulsant agent used for the treatment of epilepsy has been reported to exhibit toxic side effects on the liver and testes. The present study investigated the protective effects of kolaviron (KV, a bioflavonoid from Garcinia kola seeds) against hepatic and testicular damage in rats exposed to phenytoin. The study consisted of four groups of six rats per group. Group I rats received 2 mL/kg of corn alone while group II received 75 mg/kg of phenytoin (PHT) alone. Groups III and IV were co-treated with kolaviron (200 mg/kg KV) and vitamin E (500 mg/kg VTE), respectively, for 14 days. The antioxidant status, hepatic and reproductive functional parameters were subsequently determined. PHT treatment significantly (p < 0.05) increased superoxide dismutase (SOD) and catalase (CAT) activities, elevated lipid peroxidation (LPO) and hydrogen peroxide (H2O2) levels along with significant reduction in the hepatic and testicular levels of glutathione (GSH). Moreover, PHT exposure elicited significant increases in alkaline phosphatase (ALP) and aspartate aminotransferase (AST) levels. The significant reduction in seminal epithelium thickness and the diameter of seminiferous tubules was accompanied with marked decrease in sperm motility, sperm count, and viability in PHT-treated rats. However, antioxidant status and the functional indices of liver and testes were restored to near control levels in rats co-treated with KV and VTE. In conclusion, KV and VTE protect the liver and testes against functional impairment due to PHT treatment.

Field reproductive dynamics of the invasive slipper limpet, Crepidula fornicata

At least part of the invasive success of the slipper limpet, Crepidula fornicata, in European waters must be due to reproductive characteristics, yet the events underlying the easily-observed brooding and non-brooding periods have not yet been studied in this species. The reproductive system dynamics were therefore investigated using topological histology and quantitative histological techniques. Specimens were sampled twice monthly for 18months from Bourgneuf Bay, France, a mid-latitudinal point in the European distribution of C. fornicata. Both the testicles and ovaries showed active and resting phases, corresponding to the brooding and non-brooding periods, respectively. Maximum spermatozoan production corresponds to the female brooding period (female incubation of oviposited eggs, mid-March to late August), and allows males to possess full spermatozoan stocks at the height of fresh mature oocyte availability. The year-round presence of mature oocytes in the female gonad is misleading, since the histological aspect reveals that they are vestigial oocytes which slowly degenerate during the brooding period, possibly providing metabolites for the developing oocytes that become increasingly abundant during this period. A complete scheme of the C. fornicata reproductive cycle is presented, showing the events in the major reproductive organs.The seminal vesicle shows high inter-month variability in sperm presence, suggesting year-round copulation and sperm storage in the seminal receptacle. The seminal receptacle shows a uniform covering of spermatozoa throughout the year, suggesting rapid renewal after fertilization, again in line with multiple copulation throughout the year. Given the limited available space on the seminal epithelium, against which all spermatozoa abut, as well as polyandrous copulation, it is postulated that sperm competition may take place.

Antioxidants, cadmium-induced toxicity, serum biochemical and the histological abnormalities of the kidney and testes of the male wistar rats

The effect of different doses of cadmium [CD] on some biochemical, hormonal and histopathological parameters of the liver, kidney and testes of the Wistar rate were investigated. Cadmium in the dose range 0-40 mg/kg while causing a time-and dose-dependent decrease of the basal serum levels of alkaline phosphatase [ALP] also caused a dose-dependent increase in the serum concentration of the acid and prostatic acid phosphatases. The value of the ALP changed from 148.7+/-1.0 IU/L in the control to 53.7+/-0.098 at 40 mg/kg of cadmium. While the ACP and ACPT changed from 32.6+/-0.72 and 7 Units in the control to 54 and 17 units respectively at 40 mg/kg of CD. Furthermore cadmium also caused positively correlated dose-and time-dependent destruction of the histology of the liver, kidney and testes. These were characterized by vascular congestion, vacuolation, destruction of the seminal epithelial layers, focal necrosis of nucleus, oedema of the seminal epithelia layers, focal necrosis of nucleus, oedema of the seminiferous tubules and reduction of spermatogenesis. CD also caused granular and eosinophilic cytoplasm, enlargement of sinusoids with kupffer cells, haemorrhage and apoptosis of cells. Finally pre-treatment with vitamin C [0.0015/kg], vitamin E [1.51/g] and selenium [0.25 mg] which on their own had little or no effects on the serum basal phosphatases, hormonal and histological stability caused a reversal of the cadmium-induced biochemical, hormonal and histological toxicities of the liver, kidney and testes. These results may be explained by the oxidational/antioxidational properties of these xenobiotics and their mechanisms of actions.

Computerized Microscopy Research on Structural Biology of the Seminiferous Tubules and Interstitial Gland at the Cocks 90-120 Days Old

From the age of 90 days is clear that an end point of pseudostratified seminal epithelium, but the cell types and Sertoli cells are still prevails spermatogoniums and take the other two age as described above. There is a very intense reaction P.A.S. Take the positive step of tubular basement of the seminiferous membrane. There are many cells in semen Sertoli epithelium, in peritubulary are located myofibroblastes. From the age of 120 days in the seminal epithelium are present all cells of the seminal line. Basement membrane of seminiferous tubules is evident, and intertubular connective tissue is P.A.S. positive. Sertoli cells (cells sustentacular) from cells support undifferentiated of the gonads of prepubertal. These cells are active from point of the mitotic, contains large amounts of rough endoplasmic reticulum and produce paramesonephrotic hormone, a glycoprotein that inhibits development of female to male genitalia. At the age of 90 days it observe a quantitative reduction of intertubular. Interstitial endocrinocytes have different size, some are fusiforme, others have cytoplasm vacuolar, being involved in hormonegenesis

Microscopic studies of the seminiferous tubules and interstitial gland at the cocks 90-120 days old.

From the age of 90 days is clear that an end point of pseudostratified seminal epithelium, but the cell types and Sertoli cells are still prevails spermatogoniums and take the other two age as described above. There is a very intense reaction P.A.S. Take the positive step of tubular basement of the seminiferous membrane. There are many cells in semen Sertoli epithelium, in peritubulary are located myofibroblastes. From the age of 120 days in the seminal epithelium are present all cells of the seminal line. Basement membrane of seminiferous tubules is evident, and intertubular connective tissue is P.A.S. positive. Sertoli cells (cells sustentacular) from cells support undifferentiated of the gonads of prepubertal. These cells are active from point of the mitotic, contains large amounts of rough endoplasmic reticulum and produce paramesonephrotic hormone, a glycoprotein that inhibits development of female to male genitalia. At the age of 90 days it observe a quantitative reduction of intertubular. Interstitial endocrinocytes have different size, some are fusiforme, others have cytoplasm vacuolar, being involved in hormonegenesis.

Seasonal Changes in Testicular Cell Morphology in Domestic Male Cats (Felis catus)

The aim of this study was to asses the variation in the morphology of the seminal epithelium in relation to natural photoperiod in male cats. Tom cats (n = 240) were castrated every other week throughout the year. Each testis was fixed in Bouin's solution and cut into sections. The percentage of tubules with round spermatids (RS), elongated spermatids (ES), tailed spermatids (TS), mature spermatids (MS) and the number of Sertoli cells (SC) and Leydig cells (LC) were recorded in each sample. Testicles from males during short days (SHD) had a higher percentage of tubules with RS and ES compared to testicles from males during long days (LHD, 31.3 +/- 0.6 vs 2.1 +/- 0.6%, p < 0.001; 30.9 +/- 0.7 vs 11.0 +/- 0.7%, p < 0.001). Conversely, testicles from males during SHD had a lower percentage of tubules with TS and MS compared to testicles from males during LHD (24.5 +/- 0.8 vs 29.7 +/- 0.8%, p < 0.01; 13.1 +/- 1.2 vs 57.0 +/- 1.2%, p < 0.01). Furthermore, testicles from males during SHD had a higher number of SC and lower number of LC compared to testicles from males during LHD (11.4 +/- 0.1 vs 8.0 +/- 0.1%, p < 0.01; 19.2 +/- 1.0 vs 38.0 +/- 1.0%, p < 0.01). In conclusion, there are seasonal changes in testis cell morphology in the tom which may be related to seasonal sperm production.

Spermatogenic cells distal to the blood–testis barrier in rats lack C3 convertase regulators and may be at risk of complement-mediated injury

On most tissues, multiple membrane complement regulators (CReg) protect self-cells from damage by complement. An exception is the brain, where the blood–brain barrier provides a protected environment within which cells survive with little or no protection from complement. The testis has a functionally similar structure, the blood–testis barrier (BTB). Here, we have investigated the expression of C3/C5 convertase CReg and C3 in the normal rat testis at different ages and different spermatogenetic stages, as well as in rats in which spermatogenesis and the BTB were impaired due to a developmental deficit. Immature testis, prior to BTB formation at puberty, displayed broad expression of the ubiquitous rodent CReg Crry on all elements and no expression of CD46 or CD55. Within days of BTB formation, CReg expression was dramatically altered; Crry was expressed only in the spermatogenetic cells external to the BTB in basal layers of adult seminal epithelium. Spermatogenic cells immediately distal to the BTB at first expressed no C3/C5 convertase regulators but later acquired expression of CD46 and CD55. Staining for C3 was widespread pre-puberty, but absent distal to the BTB in mature rats. In rats with defects in spermatogenesis and BTB integrity, expression patterns of CReg and C3 resembled those in pre-pubertal normals. The relative paucity of CReg and absence of C3 synthesis distal to the BTB suggest the presence of a complement-protected environment analogous to that described in the brain, and suggest also that cells enclosed by the BTB may be susceptible to complement damage when the barrier is breached.

Testicular Damage from Anabolic Treatments with the β2-Adrenergic Agonist Clenbuterol in Pigs: A Light and Electron Microscope Study

The morphological consequences of anabolic clenbuterol treatment on the testicular parenchyma were investigated in 30 pigs at morphological and ultrastructural levels. Clenbuterol was given with food (1ppm). In the first group (n=10), treatment was maintained until slaughter (experimental period 3 months). In the second group (n=10), clenbuterol was withdrawn 2 weeks before slaughter (experimental period 2.5 months). A third group (n=10) of pigs not fed with clenbuterol served as controls. Animals were slaughtered at 9 months of age and samples of testicular parenchyma were collected for light and electron microscope studies. In the clenbuterol-treated groups, the interstitial cells showed a considerable increase in the organelles involved in testosterone production, with an increased development of the mitochondria, smooth endoplasmic reticulum, Golgi apparatus and lipid droplets compared to the control group. The seminal epithelium displayed many lipid vacuoles and evident signs of tubular involution, such as degenerating and multinucleate germ cells. Sertoli cells gave evidence of metabolic alterations such as large lipid deposits and cytolysosomes.

Quantitative modification of the testicular structure in pigs fed with anabolic doses of clenbuterol.

Morphological and structural data of the testes of thirty male pigs were recorded in order to evaluate the effects of an anabolic clenbuterol treatment. Pigs aged 6 months were randomly allocated to one of three experimental groups. In two treated groups, the animals were fed with anabolic doses of clenbuterol (1 ppm); in the CLB group (n = 10) clenbuterol was given until they were slaughtered (treatment period = 3 months) whereas in the CLBW group (n = 10) the clenbuterol was withdrawn two weeks before slaughter (treatment period = 2.5 months); clenbuterol was not given to the pigs of the control group (n = 10). Stereological estimations of the tissular volume fraction and tubular volume density were applied to quantify the structural constituents of the testes. The results showed an increased volume fraction of the testicular interstitium especially in the Leydig cell population, as a result of the clenbuterol treatment. The increase in the nuclear volume fraction of the Leydig cells was the more persistent change in the variations recorded in both treated groups with respect to the control. A regression of the seminal epithelium was also recorded in the treated animals. The rest of the structural parameters were closer to the normal figures in the CLBW group, suggesting a recovery of the testicular structure when clenbuterol was withdrawn.

Expression of xenotropic murine leukemia viruses.

The possibility that env gene products of endogenous murine leukemia viruses might function as determinants of normal cellular differentiation or in cell-cell communication has been suggested by several lines of investigation. First, the GIXgp70 molecule of strain 129 mice was found to behave as a differentiation alloantigen of T cells in that it was expressed in high levels on thymocytes but not on peripheral T cells (Stockert et al. 1971). Second, it was observed that while gp70 antigens could be found in many body tissues, particularly high levels were detected in certain anatomic sites such as the seminal vesicles and gall bladder epithelium (Lerner et al. 1976). Third, expression of gp70 on the surface of lymphocytes was shown to be augmented following stimulation with antigens or mitogens (Wecker et al. 1977; Moroni and Schumann 1975). Finally, it has been reported that some humoral and cellular immune responses could be inhibited in vitro and in vivo by anti-gp70 antibodies (Moroni and Schumann 1977; Theofllopoulos et al. 1981).

The role of the pineal gland in stress.

A short survey of the results of our previous research into the protective role of the pineal gland against stress is given. The neuroendocrine aspect of a chronic auditory stress and the neuroendocrine aspect of ulcer disease in man were studied. Auditory stress: hypertrophy and hyperplasia of pinealocytes, hyperplasia of the STH, FSH, LTH and TSH cells, hypertrophy of the nuclei and nucleoli of the neuroglandular cells of the supraoptic and paraventricular nuclei, pronounced hyperplasia of the cells of the reticular zone of the adrenal gland, involution of the seminal epithelium, hyperplasia of the Leydig cells. Ulcer disease: numerous glial plates, cavities and acervuli in the pineal gland, numerous granules and vacuoles in the FSH cells, large and eccentrical nuclei in the LH cells, hyperplasia of the cells of the reticular zone of the adrenal gland, presence of the seminal tubules marked by signs of involution, hyperplasia of the Leydig cells. The results obtained point to the secretion of androgens and the insufficiency of the antiandrogenic function of the pineal gland both in auditory stress and ulcer disease. The anticancerogenic effect of the pineal gland would be based on its antiandrogenic function.

Drug-induced histological changes in rat seminiferous tubular epithelium.

It is proposed to divide antispermatogenic compounds into four main groups on the basis of the morphological changes which they cause: a) Radiomimetic substances (e.g., Busulfan). These have a direct effect on spermatogonia and hence also on later sperm development. b) Substances inhibiting the meiotic and postmeiotic phases of spermatogenesis. These cause the seminal epithelium to disappear rapidly except for spermatogonia and Sertoli cells, which apparently remain intact (e.g., 20-438, an indenopyridine derivative). c) Substances acting hormonally (via pituitary). These severely damage Leydig cells, and there is a particularly pronounced degeneration of later stage spermatids. Sertoli cells are also affected. The tunica propria becomes thicker. The weights of the accessory sex glands decrease, and the pituitary weight increases. The peritubular tissue in the epididymis becomes thicker (e.g., 17 beta-estradiol). d) Vasoactive substances (e.g., cadmium chloride). These cause spot-like necrosis. Whole tubuli are destroyed (similar to infarction) whereas others can remain intact. Leydig cells also degenerate, and there is fibroblastic proliferation in the interstitium. The peritubular tissue in the epididymis becomes thicker and the secretion of clear cells is affected. Accessory glands lose weight.

Inhibition of spermatogenesis.

The effect upon spermatogenesis of subdermal silastic capsules containing testosterone in combination with various oral drugs was studied in groups of subfertile men. Group 1 received 25 mg norethisterone daily by mouth in conjunction with 6 norethindrone implants and 3 testosterone implants. (The release of testosterone per capsule was about 55 mg/24 hours.) 2 of the 5 patients reached azoospermia within 6 weeks; the others showed lowered sperm counts but it is possible they took the tablets irregularly. 9 weeks after discontinuing oral norethisterone all had an increasing number of sperm. Group 2 contained 4 men aged 25-32 and 3 aged 66-73. In addition to 6 sc implants of megestrol acetate and 4 sc implants of testosterone each received 25 mg norethisterone daily. 3 of the 4 young men had a drop in sperm count 6 weeks after treatment started while the 4th had an increase from 71 million to 126 million. In the 3 older men results were assessed by testicular biopsies which showed normal wide not sclerosed tubules with all steps of spermatogenesis before treatment but reduced diameter of the tubules with tubular epithelium apparently devoid of germinal elements after treatment. Also there was disorganization and depopulation of the seminal epithelium. Leydig cells seemed reduced and atrophic. Group 3 consisted of 6 men aged 26-39 with fertility problems. They received 4 sc testosterone implants plus 100 mg medroxyprogesterone acetate depot (MPA). Between Weeks 6-12 azoospermia was found in 4 and reduced in all except 1. Group 4 consisted of 5 men aged 63-74 with benign prostatic hypertrophy treated with MPA plus 6 implants of megestrol acetate and 4 of testosterone. Posttreatment biopsy showed a lack of germinal elements in the tubules the diameter of the tubules unchanged and Leydig cells partially atrophic and diminished. All patients affirmed normal sexual activity and noted no changes of libido or potency. Group 5 consisted of 5 men aged 32-62 treated with R2323 orally 5 mg twice a week for 6 weeks and then 25 mg twice a week plus 4 testosterone implants. 3 of the men showed azoospermia between 6-12 weeks the 4th had lowered sperm count but did not take all the tablets. The older man showed arrested spermatogenesis on biopsy. However libido and errections decreased appreciably 2 complained of intense perspiration at night and 1 complained of heartburn. These men also showed alterations in the blood levels of liver enzymes and an increased secretion of urobilinogen in the urine even within the 1st weeks of treatment.