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.     

Granular transformation of Sertoli cells in testicular disorders.

In order to study the granular transformation of Sertoli cells the following testicular specimens were reviewed: 58 postmortem biopsies from 21 children and 37 young adult males with normal histologic pattern; 165 biopsies from prepubertal cryptorchid testes; 38 biopsies and 18 surgical specimens from postpubertal-cryptorchid testes; bilateral biopsies from eight men with Del Castillo's syndrome, 14 men with retractile testes, and five men with obstructive azospermia; 17 bilateral and seven unilateral biopsies from 24 men with varicocele; seven unilateral biopsies plus five surgical specimens from 12 men with male pseudohermaphroditism; one biopsy and one surgical specimen from two men with macroorchidism; and the autopsy specimens from 28 adult men with acquired immunodeficiency syndrome (AIDS). Sertoli cells with eosinophilic granular cytoplasm were found in the testes of one prepubertal and four postpubertal cryptorchid males, two males with Del Castillo's syndrome, two males with retractile testes, four males with varicocele, two male pseudohermaphrodites, two males with macroorchidism, and one male with AIDS and interstitial orchitis. Histochemical and ultrastructural examination of granular Sertoli cells revealed that these cells accumulate secondary lysosomes and show scant cytoplasmic organelles. In the males with varicocele or retractile testes, these lysosomes were probably heterolysosomes that had degraded the germ cells and testicular fluid accumulated in the lumen of the ectatic seminiferous tubules of these testes. A similar mechanism is also probable in the male with interstitial orchitis that had caused germ cell destruction. In the other cases, in which the tubules showed reduced lumen and severe germ cell depletion, the abundant lysosomes are probably cytolysosomes. The development of these cytolysosomes might be related to the Sertoli cell dysgenesis present in these testes.     

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.     

Mitotic activity of Sertoli cells in adult human testis: an immunohistochemical study to characterize Sertoli cells in testicular cords from patients showing testicular dysgenesis syndrome

During puberty, normal somatic Sertoli cells undergo dramatic morphological changes due to the differentiation of immature pre-Sertoli cells in functionally active adult Sertoli cells. Sertoli cell maturation is accompanied with loss of their mitotic activity before onset of spermatogenesis and loss of pre-pubertal and occurrence of adult immunohistochemical Sertoli cell differentiation markers. Testes of infertile adult patients often exhibit numerous histological signs of testicular dysgenesis syndrome (TDS) such as microliths, Sertoli cell only (SCO) tubules, tubules containing carcinoma in situ and immature seminiferous tubules (Sertoli cell nodules). Sertoli cell tumours, however, are very rare neoplasms possibly due to the fact that the mechanism and temporal origin of neoplastic Sertoli cells underlying Sertoli cell tumourigenesis still remain unknown. To clarify the state of Sertoli cell differentiation in both immature seminiferous tubules of adult patients with TDS and Sertoli cell tumour, we compared the expression of the Sertoli cell differentiation markers vimentin, inhibin-α, anti-Muellerian-hormone, cytokeratin 18, M2A-antigen, androgen receptor and connexin43 with that of SCO tubules with hyperplasia. In addition, we demonstrated for the first time the existence of proliferating Sertoli cells by Ki67- and PCNA-immunostaining in Sertoli cell nodules of the adult human testis. Our data indicate that mitotically active Sertoli cells in Sertoli cell nodules will be arrested prior to puberty and, contrary to dogma, do not represent foetal or neonatal cells. Since all markers in Sertoli cell nodules revealed a staining pattern identical to that in neoplastic Sertoli cells, but different to that in Sertoli cells of SCO tubules with hyperplasia, it may be speculated that Sertoli cell tumours in adult men may originate from Sertoli cell nodules.     

Testis morphology in patients with idiopathic hypogonadotropic hypogonadism

BACKGROUND: Adult patients with idiopathic hypogonadotropic hypogonadism (IHH) typically present with absent puberty and therefore have prepubertal testes. IHH is recognized as one of the few curable causes of male infertility and is often effectively treated with either gonadotropins or pulsatile GnRH therapy. The objective of this study was to determine the structure of the testis prior to initiation of treatment. METHODS AND RESULTS: Eight adult IHH patients with prepubertal testes (<4 ml), with no previous gonadotropin therapy and with no history of cryptorchidism underwent open bilateral testicular biopsy prior to the initiation of hormonal treatment. The testes of all patients showed seminiferous cords separated by interstitium composed of blood vessels, connective tissue cells and collagen fibres but typical adult Leydig cells were absent. The cords contained only Sertoli cells and early type A spermatogonia. The spermatogonia mostly resided in the centre of the cords and were often large, typical of gonocytes. Sertoli cells appeared immature with ovoid nuclei devoid of infoldings and cytoplasm that lacked polarity. Tight junctional complexes commonly found connecting adult Sertoli cells were lacking. CONCLUSIONS: These results demonstrate that the immature testes from patients with the severe form of IHH possess early spermatogonia that could possibly reinitiate spermatogenesis with appropriate hormone stimulation. Therefore, the immature testis of this IHH subset resembles those of prepubertal boys and may provide important biologic and genetic insights into testicular development.     

Testicular lipomatosis in Cowden's syndrome.

Cowden's syndrome is either familial or sporadic and is associated with the predominantly postpubertal development of a variety of cutaneous, stromal and visceral neoplasms. The syndrome is associated with mutations of the PTEN gene and is closely related to Bannayan's syndrome in which macrocephaly and benign tumors, especially lipomas and hemangiomas are pathognomic. In PTEN knockout mice testicular tumors have been reported and for this reason we felt it prudent to examine the testes of our patients with genetically proven Cowden's syndrome. Seven of eight patients who underwent testicular ultrasound were found to have diffuse bilateral hyperechoic lesions. Four patients consented to testicular biopsy and on histological examination multiple foci of adipocytes were found within the testicular interstitium, with no evidence of dysplasia or preclinical malignancy. Immunohistochemical assessment of adipocytes suggested a stromal derivation without evidence of metaplasia from Leydig cells. In one case there was focal atrophy of seminiferous tubules, while in two others there was nodular periorchitis of the tunica albuginea. Biochemical evaluation of testicular function (luteinizing hormone, follicle-stimulating hormone, testosterone, sex hormone binding globulin and free androgen index), prostate-specific antigen and testicular tumor markers were normal, while seminal fluid analysis showed only minor abnormalities. The high incidence of testicular lipomatosis in our adult subjects suggests this to be an important diagnostic criterion for Cowden's syndrome.     

Sertoli cell nodules in the undescended testis: a histochemical, immunohistochemical, and ultrastructural study of hyaline deposits

AIMS: To document the morphology, immunohistochemical staining properties, and ultrastructural features of hyaline material in Sertoli cell nodules of undescended testis and contrast them with those of sex cord tumour with annular tubules (SCTAT), which is histologically similar. To highlight the need to distinguish these nodules from other Sertoli cell hyperplasias, such as intratubular Sertoli cell proliferations, which occur in specific clinical contexts. MATERIALS/METHODS: A retrospective study of 46 orchidectomy specimens from cryptorchid testes, 27 of which contained Sertoli cell nodules. Special histochemical stains, immunohistochemical stains for type IV collagen and fibronectin, and ultrastructural examination of the hyaline material were performed using tissue from paraffin wax embedded tissue blocks. RESULTS: The hyaline deposits in SCTAT and Sertoli cell nodules had similar staining patterns-periodic acid Schiff (PAS) and PAS-diastase positivity with variable staining of Martius scarlet blue and Masson trichrome. Type IV collagen immunoreactivity was seen in hyaline areas, although fibronectin was negative. Electron microscopy of hyaline areas confirmed a compact matrix identical to components of the basement membrane in the adjacent seminiferous tubules. CONCLUSION: This study describes an unusual form of Sertoli cell proliferation in undescended testes, which must be distinguished from Sertoli cell tumours and other forms of proliferation. In addition, the hyaline material within Sertoli cell nodules in the cryptorchid testis is histochemically, immunohistochemically, and ultrastructurally consistent with both matrix and fibrous components of seminiferous tubule basement membranes. Increased production of basement membrane material, with subsequent invagination into tubules, is the most likely origin of this material.     

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.     

Nuclear Bodies (Sphaeridia) in Sertoli Cells of a Man with Acquired Immunodeficiency Syndrome (AIDS) and Testicular Infection by Cytomegalovirus

Histological and ultrastructural study of an adult man with acquired immunodeficiency syndrome (AIDS) revealed multiple testicular lesions. The seminiferous tubules varied from dilated tubules with hypospermatogenesis, to tubules with Sertoli cells and a few spermatogonia, to necrotic tubules. The testicular interstitium showed abundant inflammatory infiltrates, some of them forming micro-abscesses. The Sertoli cells exhibited spherical intranuclear inclusions corresponding to both cytomegalovirus and sphaeridia. Some sphaeridia stained intensely with EDTA as granular and fibrillar portions of the nucleolus; however, many sphaeridia stained weakly as nucleolar fibrillar centers. These observations suggest that a Sertoli cell response to cytomegalovirus is the proliferation of nucleolar organizing centers that in some instances may transform to give rise to more or less abnormally developed nucleoli.     

Hyperplasia and the immature appearance of Sertoli cells in primary testicular disorders

Testicular biopsy specimens from adult patients affected with cryptorchidism, Klinefelter's syndrome, and Del Castillo's syndrome were examined by light and electron microscopy. The study revealed a high proportion of testes showing seminiferous tubules with hyperplasia of Sertoli cells (from 25 to 45 cells per transverse tubular section). These cells had an immature appearance and showed a pseudostratified distribution. The nucleus was round to ovoid and regular in outline, with a smaller nucleolus than that of mature Sertoli cells. The cytoplasm showed less development of the endoplasmic reticulum as well as of the secondary lysosomes and lipid droplets than that in mature Sertoli cells. Characteristic features of these immature Sertoli cells were abundant cytoplasmic microfilaments, elaborate interdigitations between adjacent cells, and extensive tight junctions, from basement membrane to lumen. In the cryptorchid testes, a more immature Sertoli cell was found to constitute the majority of the cells in hypoplastic zones. In Klinefelter's and Del Castillo's syndromes as well as in cryptorchid testes to a lesser degree, a transitional type of cell-from immature to mature-was also observed. These observations suggest that Sertoli cells in these primary testicular disorders reflect a congenital deficiency producing abnormal development.     

Correlation between testicular biopsies (prepubertal and postpubertal) and spermiogram in cryptorchid men

Twenty-one young men who underwent testicular biopsy and orchidopexy in infancy consulted owing to infertility and had biopsies again. The first and second biopsy specimens from these patients were compared by means of a semiquantitative study of the seminiferous tubules to evaluate the evolution of germ cells and to correlate these data with spermatozoon numbers. The infant testes showing lesions were classified into 3 types according to the mean tubular diameter and tubular fertility index: (1) slight lesions, (2) marked germinal hypoplasia, and (3) severe germinal hypoplasia. In the adult testes, spermatogenesis was evaluated by calculating the average numbers of spermatogonia, primary spermatocytes, young spermatids, and mature spermatids. These testes were classified as (1) normal; (2) having lesions in the adluminal compartment; (3) having lesions in the basal compartment; and (4) mixed atrophy. The number of differentiated spermatids was correlated with the expected number of spermatozoa in the ejaculate by a power regression curve. The observation of certain histologic lesions in the seminiferous tubules was assumed to indicate excretory duct obstruction: ectasia, indented outline of the seminiferous epithelium, intratesticular spermatocele, apical cytoplasmic vacuolation of Sertoli cells, and mosaic distribution of testicular lesions. There was a correlation between the prepubertal lesions and the degree of spermatogenesis in postpubertal biopsy specimens. The evolution of the 40 testes without regard to their location in infancy (cryptorchid or scrotal) was as follows. The 14 infant testes with a normal histologic pattern (5 testes) or minor lesions (9 testes) evolved to testes with lesions of the adluminal compartment (8 testes), mixed atrophy (4 testes), or lesions of the basal and adluminal compartments (2 testes). The 6 testes with marked germinal hypoplasia evolved to testes with mixed atrophy. The 20 testes with severe germinal hypoplasia evolved to testes with mixed atrophy (17 testes), Sertoli-cell-only tubules (2 testes), or lesions in the basal compartment (1 testis). In the 9 patients with a histologic pattern of obstruction bilaterally (6 men) or unilaterally (3 men), the expected number of spermatozoa according to the correlation curve was much higher than the actual number in the spermiogram. This means that the testes of many azoospermic men produce spermatozoa, and this finding corroborates the importance of testicular biopsy in infertility studies.     

Distinct changes in the laminin composition of basement membranes in human seminiferous tubules during development and degeneration.

We studied the distribution of laminin (Ln) chains and their integrin (Int) receptors in normal developing and adult and in atrophied human testes by using immunohistochemistry. Immunostaining for EHS Ln and type IV collagen was used to identify basement membranes (BMs). In the BM of seminiferous epithelium of fetal testis, a panel of monoclonal antibodies showed immunoreactivity for Ln alpha 1-, alpha 2-, beta 1-, beta 2- and gamma 1-chains, suggestive of the presence of Lns 1 to 3. In BM of adult seminiferous epithelium with active spermatogenesis, immunoreactivity for Ln beta 2- and gamma 1-chains was found but not for Ln alpha-chains, suggesting a complex of Ln chains not compatible with any known trimers. Instead, with polyclonal Ln antiserum and monoclonal antibody to type IV collagen, a distinct BM-like reactivity was seen. In atrophied testes, prominent immunoreactivities for Ln chains, compatible with Lns 1 to 3, were seen in the thickened BM of seminiferous tubules, hence suggestive of reappearance of fetal Lns. Among the subunits of Ln-binding Int receptors in fetal seminiferous tubules, a strong immunoreactivity for Int beta 1- and Int alpha 6-subunits was seen throughout the seminiferous epithelium, other Int subunits being found in interstitial cells. In the adult and atrophied testes, immunoreactivities for Int beta 1- and Int alpha 6-subunits were seen to be confined to the basal aspect of the seminiferous epithelium whereas immunoreactivities for Int alpha 1-, alpha 2-, alpha 3- and beta 4-subunits were seen in the myoid cells. The results show that both maturation and degenerative changes of human testes are accompanied by distinct changes in the Ln expression of BM of seminiferous epithelium, which appears to accompany epithelial differentiation of the Sertoli cells. Furthermore, they suggest the presence of a novel Ln trimer in BM of adult human seminiferous tubules.     

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.     

Reproduction in male swamp wallabies (Wallabia bicolor): puberty and the effects of season

This study describes pubertal changes in testes and epididymides and seasonal changes in the adult male reproductive organs and plasma androgen concentrations of the swamp wallaby (Wallabia bicolor). Pre-pubescent males had testes with solid seminiferous cords and spermatogenesis only to the stage of gonocytes. Their epididymides had empty lumina along their entire length. The testes of three males undergoing puberty had some lumen formation and mitotic activity. Their epididymides were similar in appearance to those of adult males but were entirely devoid of any cells within the lumen of the duct. Three other pubescent males showed full lumen formation in the testes and spermatogenesis up to the elongating spermatid stage. Their epididymides were similar in appearance to those of adult males but with no spermatozoa in the duct. However, cells of testicular origin were found in the lumen of the duct in all regions suggesting that testicular fluids and immature germ cells shed into the rete testes flow through the seminiferous tubules into the epididymis before the release of mature testicular spermatozoa. The weights of testes and epididymides of adult males showed no change throughout the year but prostate weight and plasma androgen concentrations varied significantly with season, with maximums in spring and summer and minimums in winter. The volume fraction of Leydig cells and seminiferous tubules was significantly lower in winter than in summer; but, despite this, maturing spermatozoa were found in the testes throughout the year. Females in the area conceived year-round, suggesting that seasonal changes in the male reproductive tract did not prevent at least some males from breeding throughout the year.     

The spectrum of histopathology of the testis in acquired immunodeficiency syndrome

This study underscores an unexpectedly high incidence of histologic abnormalities in 33 testes from 31 patients who died of acquired immunodeficiency syndrome. Histologic changes of seminiferous tubules were classified into five categories: "Sertoli cell only" (14 testes, 42%), hypospermatogenesis (9, 27%), peritubular fibrosis and tubular hyalinization (5, 15%), maturation arrest (4, 12%), and normal (1, 3%). Significant interstitial fibrosis was found in 18 testes and mild lymphocytic infiltration in 5. Leydig cells were increased in 4 and decreased in 12. Opportunistic infections or Kaposi's sarcoma were not found in any of these testes. Possible explanations for the high incidence of the testicular abnormalities include direct viral cytopathic effect, antisperm antibody produced by homosexual activities, and thermal damage to the germ cells due to prolonged febrile state.     

Congenital Leydig cell hyperplasia

The testes and epididymes collected at autopsy from 21 newborns showed apparent Leydig cell hyperplasia which was studied by light and electron microscopy. Twelve newborns were the sons of diabetic mothers, two had undergone rhesus isoimmunization, two were twins of a non-diabetic mother, three had Beckwitz-Widemann's syndrome, and two had leprechaunism. In the first two groups the placentas were also collected and studied. All the testes showed normal seminiferous tubules and diffuse Leydig cell hyperplasia in the testicular interstitium. In addition one son of a diabetic mother and another with Beckwitz-Widemann's syndrome presented multiple Leydig cell nodules in the mediastinum testis and epididymis. The number of Leydig cells per unit area of the testis was calculated on histological sections stained with the peroxidase-anti-peroxidase method for the detection of testosterone. These numbers varied from 1.4 to 3.2 times those found in age-matched controls, except for the two testes with nodular hyperplasia in which the increase in Leydig cells was even greater. The differential diagnosis between Leydig cell hyperplasia, ectopic adrenal cells and leydig cell tumour is discussed. It is proposed that the cause of congenital Leydig cell hyperplasia might be related to placental secretion of human chorionic gonadotrophin.     

Malignant sex cord–stromal tumour in a patient with the androgen insensitivity syndrome

A malignant sex cord–stromal tumour that occurred in a 56-year-old patient with the androgen insensitivity syndrome is reported. Although hamartomas composed of sex cord cells are common in the testes of patients with this syndrome, unequivocal neoplasms of sex cord type are rare. The tumour described herein most closely resembled, but lacked the overall morphology of, a juvenile granulosa cell tumour, and Charcot-Böttcher filaments, indicative of Sertoli cell differentiation, were seen on electron microscopy. The features of the androgen insensitivity syndrome and the various tumours that have been reported in patients with this syndrome are briefly reviewed.     

Atypical development of Sertoli cells and impairment of spermatogenesis in the hypogonadal (hpg) mouse

Testes of hypogonadal (hpg) mice show arrested postnatal development due to congenital deficiencies of gonadotrophin-releasing hormone (GnRH) and gonadotrophin synthesis and secretion. Follicle-stimulating hormone (FSH), androgen or oestrogen treatment restore qualitatively normal spermatogenesis in hpg testes. Understanding the cellular and molecular changes accompanying hormone-induced spermatogenesis in hpg mice requires detailed morphological analyses of the germ cells and Sertoli cells in the untreated hpg testis. We compared seminiferous epithelial cytology in adult hpg, immature and adult wild-type mice using unbiased optical disector-based stereology, immunolocalization of Sertoli cell microtubules (MT), espin (a component of the blood-testis barrier), markers of Sertoli cell maturity (p27(kip1) and WT-1), and electron microscopy. Hpg testes had marked reductions in weight, seminiferous cord volume and length, and severe spermatogenic impairment with germ cells per testis < 1% of adult wild-type testes. Sertoli cell nuclei expressed WT-1 in hpg testes, but often were centrally located, similar to 9-14-day-old wild-type testes, and they expressed p27(kip1), indicating that hpg Sertoli cells were post-mitotic. Hpg testes had significantly (P < 0.05) reduced Sertoli cells per testis (0.56 million) compared with 10-day wild-type (1.15 million) and adult wild-type testes (2.06 million). Immunofluorescence labelling of normal adult Sertoli cells showed supranuclear MT columns and basally located espin, but these features were absent in 10-day-old and hpg Sertoli cells. Hpg Sertoli cells showed pleomorphic nuclear ultrastructure with mature-type nucleoli, similar to normal adult-type Sertoli cells, but hpg Sertoli cells exhibited incomplete tight junctions that lacked ectoplasmic specializations. We conclude that in hpg mice, chronic gonadotrophin insufficiency restrains Sertoli cell proliferation and maturation, forming pseudo-adult-type Sertoli cells that are incapable of supporting germ cell proliferation and maturation.     

The influence of vasovasostomy on testicular alterations after vasectomy in Lewis rats

The occurrence of alterations in testicular weight and morphology after vasectomy and vasectomy reversal by vasovasostomy was studied in Lewis rats. Animals were studied 3, 4, and 7 months after bilateral vasectomy or a vasectomy followed 3 months later by vasovasostomy. Other rats served as sham-operated controls. The weights of the testes in vasectomy and vasovasostomy animals fell into two groups-small testes weighing less than 0.88 g and normal-sized testes of 1.2 g or more. When the extent of testicular alterations was estimated in sections for light microscopy by use of a semiquantitative testicular biopsy score count (TBSC), the morphology of the testes corresponded closely to the testis weight (r = .94), small testes having correspondingly low TBSC scores. In severely altered small testes, the seminiferous tubules were narrower than in sham-operated rats, and numbers of germ cells were greatly depleted. Many tubules contained only Sertoli cells and spermatogonia, although spermatocytes were present in a minority of tubules. A few seminiferous tubules contained multinucleate spermatids. Electron microscopy of severely altered tubules revealed closely apposed processes of Sertoli cells, which contained filaments, microtubules, and endoplasmic reticulum. In contrast, testes with normal weight in vasectomy and vasovasostomy groups resembled those of the sham-operated animals. Comparison of distributions of testicular biopsy score counts demonstrated differences between vasectomy and vasovasostomy groups as time after operation increased. At the 3-4-month intervals, approximately one-third of the testes were severely altered in both vasectomy and vasovasostomy groups.(ABSTRACT TRUNCATED AT 250 WORDS)