Early testicular changes after vasectomy and vasovasostomy in Lewis rats

The testes of Lewis rats were studied at intervals from 2 weeks to 3 months after bilateral vasectomy, vasectomy followed 1 month later by vasovasostomy, or sham operations. Aims were to determine the nature of early alterations after vasectomy, and to determine whether vasovasostomy after 1 month would result in reversal of vasectomy-induced changes. Approximately one-fourth of the testes in the vasectomy and vasovasostomy groups displayed histological changes, which consisted mainly of depletion of germ cells. The extent of the depletion varied greatly in different seminiferous tubules. In testes altered in this way, no abnormal infiltrations of lymphocytes, macrophages, or other cells were observed in the seminiferous epithelium or in the interstitium. The rete testis and straight tubules were normal in testes with altered seminiferous epithelium. A few testes in the vasectomy and vasovasostomy groups had necrotic centers. The results suggest that depletion of germ cells occurred as a result of shedding from the seminiferous epithelium into the lumen of the tubules. A cellular immune response, such as occurs in experimental allergic orchitis in other species, did not appear to be responsible for the observed loss of germ cells. This suggests a possible role for humoral antibody in this model, since there is an association between testicular changes and serum antisperm antibodies at longer intervals after vasectomy. Testicular alterations were not reversed by performance of a vasovasostomy 1 month after vasectomy.     

Testicular Biopsy Score Count After Vasectomy in Albino Rats

Context: One of the challenging problems faced by the entire world is population explosion. The vasectomy is simple, safe, quick and effective vital method of male sterilization. In the recent years a large number of vasectomies have been performed in India, since the inception of National Family Planning Program in 1956. Thus the number of request for the restoration of fertility is also increased. Aim: The present study was carried out to know whether the testicular biopsy score count, indicating the process of spermatogenesis remains normal after vasectomy. Material & Methods: The testicular biopsy count of testes of 50 male albino rats was studied one, two, three and four months after vasectomy, in 10 male albino rats of each case and 10 male albino rats served as control. Result: After vasectomy seminiferous tubules are cut in various planes covered externally by connective tissue stroma with normal microscopic picture. The spermatogonia, spermatocytes, spermatids, Sertoli cells and spermatozoa show normal structure with normal size blood vessels in interstitial connective tissue, in vasectomised and control rats. In some seminiferous tubules granular cytoplasmic vesicle like structures are seen filling the lumen and spermatids in metamorphosis phase to spermatozoa. Many round or elongated heads of spermatozoa are present at apical portion of Sertoli cells. The control rats as well as vasectomised rats at four after vasectomy have shown the testicular biopsy score count of nine (9) and ten (10) on TBSC of Johenson. Conclusion: On critical analysis it is concluded that the testicular biopsy score count remains normal at four months after vasectomy.     

Degenerated tubules in the guinea pig testis after long-term vasectomy or sham operation

The testes of eight unilaterally vasectomized and six sham-operated Dunkin Hartley guinea pigs were examined 3 years after operation by wax and resin histology and transmission electron microscopy. Degenerated tubules are reported that were common on the side of vasectomy but also found in the contralateral testes and in the controls. A central accumulation of macrophages, rich in phagocytosed debris including spermatozoal fragments, was surrounded by attenuated Sertoli cells, a markedly thickened basement membrane and myoid cells. At some sites macrophages impinged directly on the basement membrane. They probably represented highly degenerated seminiferous tubules. The study suggests that the response to injury of seminiferous tubules may show species variations. Macrophages did not feature in the degenerated seminiferous tubules we reported following vasectomy in the rat. However, the rat showed striking changes in the morphology of the basal laminae and myoid cells which did not occur in the guinea pig. Pathological changes have been reported in the human testis following vasectomy but their etiology is unclear. Studies in the guinea pig are enhancing understanding of the mechanisms and features of testicular damage.     

Androgen insensitivity syndrome: an immunohistochemical, ultrastructural, and morphometric study

OBJECTIVE: To evaluate the morphometric, immunohistochemical, and ultrastructural lesions of the testes in prepubertal and adult patients with androgen insensitivity syndrome. METHODS: We examined the testicular biopsy using immunohistochemistry for vimentin, smooth muscle actin, and collagen IV antigens. Quantification of seminiferous tubules and testicular interstitium was performed in prepubertal and adult patients with androgen insensitivity syndrome and results were compared with normal testes from both infants and adults. RESULTS: The adult testes presented nodular and diffuse lesions that consisted of Sertoli-cell-only seminiferous tubules. Two types of Sertoli cells could be distinguished, namely, immature vimentin-positive Sertoli cells and nearly mature Sertoli cells. In the nodules, the lamina propria was thin and contained a scant number of actin-positive peritubular cells. Leydig cells were hyperplastic. The prepubertal patients showed only diffuse lesions characterized by Sertoli cell hyperplasia, decreased germ cell numbers, and a discontinuous immunoreaction to collagen IV. CONCLUSIONS: The testicular lesions in androgen insensitivity syndrome are probably caused by primary alterations that begin during gestation. These lesions become progressively more pronounced at puberty, when the nodular lesion pattern (adenomas) is completely developed.     

Morphological alterations and distribution of occludin in rat testes after bilateral vasectomy

The aim of study was to investigate the fate and the morphology of the cells which constitute the spermatogenic line, and to determine the distribution of occludin in the testis in adult vasectomized Wistar rats. The rats were divided into two groups: control group (sham-operated) and vasectomized group. One, 3 and 6 months after sham and vasectomy operations, testis samples were examined. The weight of the testes was found to be reduced 3 and 6 months after vasectomy. There was vacuolization in the seminiferous tubules one month after vasectomy. The tubules showed severe atrophy 3 and 6 months after vasectomy. The occludin immunolabeling in the 3- and 6-month groups was weak and diffuse, and the density of the protein was found to be decreased. The increase in the number of apoptotic cells was accompanied by a time-dependent decrease in the number of haploid, diploid and tetraploid cells. This study demonstrated that vasectomy causes degeneration in the seminiferous tubules with alterations in occludin distribution with a decrease in the number of spermatogenic cells. Moreover, these alterations increase in a time-dependent manner.     

淋巴管阻断对大鼠睾丸生精上皮的影响

用外科手术的方法将正常成年ＳＤ大鼠双侧睾丸淋巴管阻断后，观察术后不同时间睾丸生精上皮的组织学变化。术后２天出现生精上皮的形态改变，生精细胞排列松散，部分精子细胞脱落，聚集在管腔部位。术后６天多数曲细精管的精子细胞全部脱落。假手术对照组，睾丸生精上皮具有正常的形态结构。     

Spermatogenesis in the vasectomized monkey: Quantitative analysis

The seminiferous epithelium in mature vasectomized Macaca fascicularis was examined quantitatively to assess spermatogenesis. Monkeys were bilaterally vasectomized and controls were bilaterally sham operated. At postoperative periods of 10 and 18 months, groups of monkeys were castrated and their testes prepared for morphologic analysis. Diameters were measured in 100 cross sections of seminiferous tubules from each animal. Numbers of spermatogonia (Ad and Ap), preleptotene spermatocytes, pachytene spermatocytes, and step 7 spermatids, relative to Sertoli cell nucleoli, were counted in stage VII tubules. Tubule diameter and germ cell numbers per Sertoli cell nucleoli were not altered by vasectomy. Our study demonstrates quantitatively that spermatogenesis in the monkey is not inhibited up to 18 months following vasectomy.     

Macro-orchidism: light and electron microscopic study of four cases.

A hormonal and quantitative light microscopy study of one man with macro-orchidism associated with mental retardation and fragile X chromosome (case no. 1) and three men with idiopathic macro-orchidism (cases no. 2 to 4) is reported. Hormonal study revealed slightly increased follicle-stimulating hormone serum levels in cases no. 1 to 3. The testes from cases no. 1 (orchidoepididymoectomy specimen) and 2 (testicular biopsy) presented interstitial edema and three different tubular patterns that were arranged in a mosaic-like manner. Type I tubules had an increased diameter (less than 220 microns), dilated lumen, and thin seminiferous epithelium usually consisting of Sertoli cells, spermatogonia, primary spermatocytes, and sometimes a few spermatids. Type II tubules had a normal diameter (180 to 220 microns) and germ cell development varied between complete spermatogenesis and Sertoli-cell-only tubules. Type III tubules had decreased diameter (less than 180 microns), atrophic seminiferous epithelium, and thickened tunica propria. The appearance of the nuclei of the Sertoli cells in the three types of tubules could be either mature or immature. Some of the mature Sertoli cells presented a granular cytoplasm. A few of these granular cells grouped together, forming nests that protruded into the tubular lumen. The testicular biopsies from cases no. 3 and 4 only presented type II tubules that contained both mature and immature Sertoli cells. Quantitative study revealed that the large testicular size was principally due to an increased tubular length in all four cases. Although the seminiferous tubule lesions and interstitial edema suggest an obstructive process, the testicular excretory ducts (studied in case no. 1) appeared normal or only slightly dilated. It is possible that the seminiferous tubule lesions (dilated lumen and germ cell depletion) might be secondary to the Sertoli cell lesions (granular cytoplasm and nuclear immature-like pattern.     

Focal orchitis in undescended testes: discussion of pathogenetic mechanisms of tubular atrophy.

OBJECTIVE: To evaluate seminiferous epithelium lesions in adult cryptorchid testes showing lymphoid infiltrates in seminiferous tubules and interstitium (i.e., focal orchitis). Also, to consider the possible role of this lesion in the etiology of tubular atrophy. METHODS: We performed a histopathologic study of the cryptorchid testes and adjacent epididymides removed from 50 adult men who had not been previously treated for cryptorchidism. The study included morphologic and semiquantitative evaluation of seminiferous tubule pathology (according to germ cell numbers), Sertoli cell morphology, tubular lumen dilation, rete testis pattern (normal, hypoplastic, or cystic), and epididymal pattern (normal or epididymal duct hypoplasia). The study also included immunohistochemical evaluation of immune cell markers. The results were compared with clinical and laboratory findings. RESULTS: Focal lymphoid infiltrates (mainly lymphocytes) in seminiferous tubules and interstitium were found in 22 patients (44%), all of whom had unilateral cryptorchidism. The course of orchitis was asymptomatic, and laboratory data were normal. According to the seminiferous tubule pathology, a variety of histopathologic diagnoses, were made: (1) mixed atrophy consisting of Sertoli cell-only tubules intermingled with tubules showing maturation arrest of spermatogonia (11 testes, 4 of which also showed hyalinized tubules); (2) Sertoli cell-only tubules plus hyalinized tubules (4 testes); (3) Sertoli cell-only tubules (3 testes); (4) intratubular germ cell neoplasia (2 testes, 1 of which also showed hyalinized tubules); (5) complete tubular hyalinization (1 testis); and (6) tubular hyalinization plus some groups of tubules with hypospermatogenesis (all germ cell types were present although in lower numbers, 1 testis). Dysgenetic Sertoli cells, that is, Sertoli cells that had undergone anomalous, incomplete maturation, were observed in all nonhyalinized seminiferous tubules with inflammatory infiltrates. Tubular ectasia was observed in 13 cases. The rete testis was hypoplastic and showed cystic transformation in 18 testes, and the epididymis was hypoplastic in 15 testes. CONCLUSIONS: The causes of these focal inflammatory infiltrates are unknown. It is possible that tubular ectasia and Sertoli cell dysgenesis are involved and that these alterations cause a disruption of the blood-testis barrier and allow antigens to enter the testicular interstitium, giving rise to an autoimmune process.     

Annulate lamellae in guinea pig Sertoli cells

Unilateral torsion of the spermatic cord was surgically induced in 24 Hartley strain guinea pigs. Groups of six animals were sacrificed 4, 8, 12, and 16 months after the surgery and testes were excised. Nine animals has severely damaged testes. Extensive study on the Sertoli cells of each of these nine animals was carried out after testicular tissues were processed for electron microscopy following the usual procedure. The majority of the affected seminiferous tubules contained a single layer of Sertoli cells without any differentiating germ cells. The Sertoli cells were vacuolated and contained highly lobulated nuclei. Each nucleus contained a nucleolus. The Sertoli cells contained an elaborate annulate lamellae system. The membranous portion of the annulate lamellae was associated with the rough and smooth endoplasmic reticulum. Close association of the annulate lamellae with the lysosomes and lipid droplets was found to be a consistent feature. Although it was not possible for us to predict the functional significance of these annulate lamellae, the present investigation clearly established for the first time, the presence of an annulate lamellae system in the Sertoli cell of a rodent species.     

Changes in seminiferous tubules after vasectomy

The histologic, immunohistochemical, and ultrastructural changes in the seminiferous tubules (ST) of 17 healthy adult males who had been vasectomized between 1 1/2 and 5 years are reported. There was minimal spermatogenesis in 4 cases. 8 of the cases underwent electron microscopy examination and 4 showed evidence of minimal histological spermatogenesis. The ST showed a thickening of the basement membrane and heavy deposits of lipofuchsin in the Sertoli cells (SC) seen as lipid infiltration. The spermatogenic cells presented variable changes characterized by the disorientation of cells, maturation arrest, and premature sloughing. No immune complex deposits were seen. Of the 9 cases followed, pregnancy occurred in 2 following vas reanastomosis; a regenerative capacity of the ST was seen in 6 cases. The follow-up studies also show that the morphological alterations initially produced by the vasectomy have little affect on the appearance of spermatogenesis after vas reanastomosis. Thus, we see that the vasectomy exerts its major effect on the SC and that the damage to these cells alters the testicular environment. However, these changes are apparently reversible following vasovasostomy.     

Effect of vasectomy on the seminiferous tubule boundary zone in the Albino Swiss rat

The boundary zone of a seminiferous tubule consists of the basement membrane of the seminiferous epithelium, its myoid cells, and their basal laminae. This study examines the boundary zones of seminiferous tubules in healthy and degenerated testes following long-term, left-sided vasectomy in the rat and compares them to those of sham-operated controls and adult rats exposed in utero to the antiandrogen, flutamide. Degenerated tubular profiles showed similar changes, irrespective of whether the degeneration was ipsilateral or bilateral. In transverse tubular profiles, the basal laminae of the seminiferous epithelium and the myoid cells became more undulating, that of seminiferous epithelium showing complex folding. The collagen layer of the boundary zone, which lies between the basal laminae of the seminiferous epithelium and the myoid cells, thickened and its fibers became irregularly orientated. Rather than being flattened as in controls, the region of the myoid cell near the nucleus and the nucleus itself developed triangular profiles in the transversely sectioned tubules. Similar features were also seen in the degenerated tubules of rats exposed to flutamide. The changes in the boundary zone are not specific for vasectomy and probably reflect reduction in the cross-sectional area of tubular profiles and possibly in their length. We also noted occasional leukocytes infiltrating the boundary zone; they may have increased in number in those tubules that showed degeneration following vasectomy.     

Morphological and histochemical characteristics of the lamina propria in scrotal and abdominal testes from postpubertal boars: correlation with the appearance of the seminiferous epithelium

This study was undertaken to investigate the morphological characteristics and lectin affinity of the testicular lamina propria in healthy boars and in unilateral and bilateral abdominal cryptorchid boars. The lamina propria of scrotal testes from healthy boars and unilateral cryptorchid boars was constituted by an innermost noncellular layer, the basal lamina, and by 2 layers of peritubular cells, each separated by a fibrous layer. The noncellular layers contained collagen fibres and glycoconjugates with abundant N‐acetylgalactosamine, galactose, fucose, N‐acetylglucosamine and neuraminic acid residues. The inner peritubular cell layer was composed of myoid cells, the outer layer of fibroblasts. In the abdominal testes of unilateral and bilateral cryptorchid boars, the lamina propria of nondegenerating and degenerating seminiferous tubules appeared thickened due to an increased content of collagen fibres and glycoconjugates. Glycoconjugates showed decreased amounts of fucose, neuraminic acid and galactose, and increased amounts of N‐acetylglucosamine residues. The basal lamina formed infoldings toward the seminiferous epithelium and contained small cells. Both inner and outer peritubular cells were fibroblasts of immature appearance. In degenerated seminiferous tubules of bilateral cryptorchid boars, the lamina propria was composed of a thickened and collagenised basal lamina, without peritubular cells and with a low content of glycoconjugates. In scrotal testes, therefore, the lamina propria was implicated in tubular contractility and in mediating the communication and the substrate diffusion between seminiferous tubules and interstitial tissue. Cryptorchidism induced morphological and histochemical alterations in the lamina propria of abdominal testes, which may be linked to evidence from other studies of lack of tubular contractility and defective cell–cell communication and substrate diffusion. The severity of these anomalies correlated with the severity of Sertoli cell alterations.     

Histologic changes in the mouse testis after treatment with gossypol tetra-acetic acid

The effect of oral administrations (20 or 40 mg/kg body weight/day, for 21 days) of gossypol tetraacetic acid on the testis of the Parkes strain mouse was investigated. Gossypol treatment did not affect the body weight or testicular weight, but caused a significant depression in the weight of the seminal vesicle. Histologically, the testes in mice treated with gossypol possessed regressed seminiferous tubules showing the exfoliation of germ cells, the occurrence of giant cells, a disorganization of the germinal epithelium, the degeneration of germinal elements, intraepithelial vacuolation and dislocation of the Sertoli cells into the luminal portion. However, the effect of gossypol was not uniform, and normal features were also observed in the majority of the tubules in the testes of the gossypol-treated mice. When quantitatively analysed, the frequency of regressed seminiferous tubules was significantly higher in the testes in the treated mice than the controls. The results suggest that the gossypol treatment induces non-uniform regressive changes in the seminiferous tubules in the mouse testis.     

The organization of the seminiferous epithelium in the mouse testis following ligation of the efferent ductules. A light microscopic study

In order to more fully assess and determine the relationship between the developing germ cells and the Sertoli cell epithelium, efferent ductules of Swiss albino mice testes were ligated and the effects observed. This method stretched the walls of the seminiferous tubules and thus reduced the stratification and complexity of the epithelium. At 48 hours postoperation, the testes were removed in a manner to prevent the escape of accumulated fluid. A marked size difference between the ligated and sham-operated testes was noted. Tissues were fixed in 3% phosphate buffered glutaraldehyde solution and later prepared for sectioning and examination by the light microscope. The seminiferous tubules in the ligated testes had relatively large lumens which contained spermatozoa, and the tubule epithelium was reduced in height. The various stages of cellular associations of the cycle of the epithelium were retained. Defined aggregations of germ cells grouped in specific association with the Sertoli cell elements were observed. The epithelium assumed the form of a series of parallel ridges at right angles to the tubules. Longitudinal sections of the tubules revealed pillarlike epithelial profiles. Each pillar consisted of Sertoli cell cytoplasm together with 2 generations of spermatids. The older generation of spermatids was embedded within the Sertoli cell and the younger generation along the sides. It is suggested that each generation within a ridge constitutes a single clone. The cytoplasmic bridges joining the spermatids and their attachments to the Sertoli cells are thought to determine the organization and structure of the rid ges. Several illustrations show the histological details of the structure.     

The effects of pre- and postnatal exposure to the nonsteroidal antiandrogen flutamide on testis descent and morphology in the Albino Swiss rat

Exposure of male Albino Swiss rats to the nonsteroidal antiandrogen flutamide during the period from gestational day (d) 10 to birth resulted in feminisation of the external genitalia and the suppression of growth of the male reproductive tract. In adulthood, testes were found to be located in diverse positions. True cryptorchidism occurred in 10% of cases, whereas 50% of testes descended to the scrotum and 40% were located in a suprainguinal ectopic region. Varying degrees of tubule abnormality were seen in the testes of flutamide-treated animals, ranging from completely normal tubules with full spermatogenesis (and the expected frequency of the stages of spermatogenesis) to severely abnormal tubules lined with Sertoli cells only. For each individual testis, the overall severity of tubule damage was strongly correlated with its adult location, with intra-abdominal testes worst affected and scrotally-located testes least; only the latter contained normal tubules. Similarly, intra-abdominal testes were the smallest in weight and contained the least testosterone. By contrast, postnatal treatment of male rats with flutamide from birth to postnatal d 14 did not impair development of the external genitalia, the process of testicular descent or adult spermatogenesis. These findings confirm that androgen blockade during embryonic development interferes with testicular descent but also demonstrate that (1) prenatal flutamide treatment per se has a detrimental effect on adult testis morphology but (2) the degree of abnormality of the testes is strongly influenced by location.     

Testicular dysfunction induced by penconazole fungicide on male albino rats

In the present study, penconazole fungicide was examined for its affect on the morphology and function of testes in rats. Male rats were orally administered penconazole at a dose of 50 or 100 mg/kg, three times/week, for 9 months. Testosterone hormone level was measured using enzyme-linked immunosorbent assay (ELISA). Testicles were submitted for histopathological examination using light microscope. Testicles were exposed for more investigation using transmission electron microscope. Quantitative analysis of seminiferous epithelial cycle and Leydig cells were obtained. The results revealed that a significant decrease in testosterone hormone level than the control group. Light microscope examination showed necrotic and degenerative changes in testes at the level of seminiferous tubules. Sertoli, Leydig, and germ cell numbers showed significant depletion. Ultrastructural investigation showed Sertoli and Leydig cells had several morphological alterations. Spermatogonic cells showed multiple features of apoptosis. From the previous findings, we concluded that penconazole fungicide induced structural and functional testicular impairment. The use of penconazole as a fungicide must be restricted and regularly monitored in the environment.     

Histologic classification of undescended testes

On the basis of testicular biopsy study in 203 patients and study of a second biopsy specimen from 27 of these patients, prepubertal undescended testes were classified into four categories according to the mean tubular diameter, the tubular fertility index, and the Sertoli cell index. Type I cases (testes with minimal lesions) were characterized by a normal mean tubular diameter and normal tubular fertility and Sertoli cell indexes or slight tubular hypoplasia. This group represented 26 per cent of the undescended testes. The corresponding lesions can be observed from two years of age onward and are probably acquired. After puberty normal spermatogenesis occurs. Type II cases (24 per cent of the undescended testes) included testes with marked germinal hypoplasia as well as slight or marked tubular hypoplasia and a normal Sertoli cell index. After puberty these testes develop a degree of marked hypospermatogenesis, maturation arrest, or Sertoli cells with only isolated spermatogonia and primary spermatocytes. In type III cases (testes with diffuse tubular hypoplasia) the mean tubular diameter and the tubular fertility and Sertoli cell index values were severely reduced. This group represented 33 per cent of the undescended testes, and after puberty most of them showed seminiferous tubules with exclusively adult Sertoli cells. Type IV testes (diffuse Sertoli cell hyperplasia) were associated with a nearly normal mean tubular diameter and variable tubular fertility index values and represented 17 per cent of all the undescended testes. After puberty Sertoli cells do not mature completely, and therefore in spite of the earlier tubular fertility index, the germinal cell line does not reach adult development. Although early orchiopexy prevents tubular fertility index and mean tubular diameter deterioration due to the noxious effects of temperature in type I testes, we believe that there is no such benefit in the other types. These patients may present only slight modifications in these indexes.     

Endocrine profile and testicular histomorphometry in adult rat offspring of diabetic mothers

This investigation was conducted to evaluate the effect of maternal diabetes on fetal testicular structure and function, and reproductive hormones levels. Sixteen female rats were divided into two groups. Diabetes was induced in one group by alloxan. Blood was collected from 90-day-old male offspring of both groups, and the level of blood glucose, testosterone, FSH and LH in their serum was measured. Weight, volume and various histological parameters of testes were determined. A significant increase in blood glucose and decrease in LH, FSH and testosterone in sera of offspring of diabetic mothers (ODM) were observed. The weight and volume of testes in the ODM were 22.7 and 22.9% higher, respectively, than those of the control group (P < 0.05), while the ratio of testes to body weight did not change significantly. The number of seminiferous tubules increased (+21%) significantly (P < 0.05), while thickness of the testicular capsule (−25%), number of Leydig cells (−15.6%), number of Sertoli cells (−14.9%), number of spermatogonia (−26.3%) and diameter of seminiferous tubules (−11%) showed significantly reduced values in the ODM compare to the control. In conclusion, maternal hyperglycemia has a deleterious effect on testicular parameters during fetal life, which will affect reproductive endocrine during postpuberty.     

Morphological and biochemical changes in the adult male rat reproductive system following long-term treatment with 1,2-dibromo-3-chloropropane

Adult Long-Evans male rats were treated with various dosages of pure or technical grade 1,2-dibromo-3-chloropropane (DBCP), epichlorohydrin (Epi), or allyl chloride (AC) for 1, 3, or 6 months on a daily basis. AC, which is the substrate for the production of DBCP, and Epi, which is a contaminant and/or metabolite of DBCP, had no effect on any of the parameters of the male reproductive system studied. The deleterious effects on male reproduction are therefore attributable specifically to DBCP. The effects of DBCP were dose and duration dependent. At the lowest dose (1 mg/kg) DBCP did not have any discernible effects on the male reproductive system. By 3 months of treatment at the intermediate dose of 5 mg/kg, the morphology of the testis ranged from normally appearing seminiferous tubules to ones which contained Sertoli cells only. At 6 months of treatment there was a reduction in the weights of the testes and sexual accessory glands. At the highest dose, the majority of the rats showed advanced testicular regression by 1 month of treatment. The most extreme testicular regression was observed in the 6-month treatment group. Almost all of the seminiferous tubules of all of the rats were composed of Sertoli cells only. In some of the animals, a few isolated seminiferous tubules contained an occasional spermatogonium or primary spermatocyte. Some of the Leydig cells of the rats in this group showed morphological evidence of atrophy as evidenced by the clumping of chromatin and paucity of stainable cytoplasm. This was confirmed by lower levels of intratesticular testosterone, a significant reduction in the number of luteinizing hormone (LH) receptors and increased serum levels of LH and follicle-stimulating hormone (FSH). From these results we conclude that DBCP is a specific male gonadotoxin and that the effects are not a result of contamination or metabolism. The effects appear to be a direct action at the testicular level because feedback inhibition to the pituitary gland was adversely affected.