Proliferation and apoptosis of spermatogonia in postpuberal boar (Sus domesticus) testes with spontaneous unilateral and bilateral abdominal cryptorchidism

Cryptorchidism is a frequent male sexual disorder in mammals, which affects the histology of the tunica propria, interstitial tissue, blood vessels, seminiferous epithelium and testis functioning. In this paper, proliferation and apoptosis were examined in the seminiferous epithelium of both testes from unaffected boars and from boars suffering unilateral and bilateral cryptorchidism. In germ cells, proliferation was studied using the immunohistochemical PCNA technique, and apoptosis was analysed by in situ TUNEL labelling. An index was obtained for the proliferation and apoptosis observed in seminiferous tubules. In abdominal testes the epithelium contained few spermatogonia and Sertoli cells. In the testes of unaffected boars, numerous spermatogonia proliferated, whereas in cryptorchid testes such proliferation was lower and the proliferation/apoptosis ratio diminished. In the unaffected group, the TUNEL-positive germ cells were spermatogonia and spermatocytes in different phases of meiosis. In abdominal testes, the TUNEL-positive germ cells were spermatogonia alone. The apoptosis index of both abdominal and scrotal testes was similar. In conclusion, spontaneous cryptorchid testes showed a lower rate of spermatogonia proliferation in the seminiferous epithelium.     

Fine structure of boundary tissue of the seminiferous tubules in the scrotal and abdominal testes of naturally unilateral cryptorchid West African dwarf goats

The boundary tissue of the seminiferous tubules in the scrotal and abdominal testes of naturally unilateral cryptorchid West African dwarf goats comprised an inner non-cellular, a middle cellular and peripheral cellular lamellae. In the scrotal testes, these components were compact and their arrangement conformed to that described for other domestic ruminants except that here, the basal lamina associated with the seminiferous epithelium was homogeneous and in tact. Alterations due to cryptorchidism as observed in the contralateral abdominal testes include general loss of compactness due to depletion and disorganization of structural extracellular materials like basal lamina coat of myoid cells and collagen fibrils, the splitting of the basal lamina of the seminiferous epithelium into 8-12 thin layers, poor differentiation of the myoid cells and the accumulation of lipid droplets within their cytoplasm. It is concluded that the normal caprine boundary tissue conforms entirely to the characteristics of 'Type C' category in the existing classification. The ultrastructural alterations due to abdominal retention of the testis resemble the testicular changes ascribed to the disturbance of pituitary-testicular hormonal axis.     

Effects of body temperature on the expression and localization of meiosis-related proteins STRA8 and SCP3 in boar testes

Body temperature could lead to interruption of spermatogenesis, but the molecular mechanism was still unclear. Cryptorchidism was defined as the failure of testes to enter the scrotum, which exposed the testes to body temperature. Meiosis was a unique feature of germ cell development. Whether cryptorchidism damage the initiation of meiosis in boars had not been reported. The aim of this study was to determine whether spermatogonia in the cryptorchid testes entered into meiosis by detecting meiosis-related markers stimulated by retinoic acid gene 8 (STRA8) and synaptonemal complex protein 3 (SCP3). Three boars with spontaneous unilateral abdominal cryptorchidism were used. The testis located in the abdomen was cryptorchidism group, the scrotal testis of the same animal was used as control. HE results showed that only Sertoli cells, and a few spermatogonia remained in the seminiferous tubules, and no spermatids were seen compared with the control. Immunohistochemistry results showed that in both control and cryptorchidism group, STRA8 was mainly expressed in the nucleus of spermatogonia and spermatocytes. In control group, SCP3 was expressed in the nucleus of spermatocytes. In cryptorchidism group, SCP3 immunopositive cells were also observed. qRT-PCR and Western Blot results showed that the mRNA and protein levels of STRA8 and SCP3 were significantly decreased in cryptorchid boars. The expression of STRA8 and SCP3 in cryptorchidism suggested that spermatogonia could still enter meiosis in cryptorchid boars.     

Lamina propria of sex cords in human fetal testis: an immunohistological and stereological study

Testicular peritubular cells are located in the lamina propria of seminiferous tubules. These cells, significantly contributing to the basal membrane of seminiferous epithelium, have been studied in a number of species. However, there is a lack of data on the development of the lamina propria in the human testis. The aim of our survey was to investigate the characteristics of the lamina propria and, in particular, peritubular cells in the fetal human testes by immunohistological and stereological methods. Therefore, testes (14–39 weeks of gestation, n=45) were dissected and fixed in a 4% buffered paraformaldehyde solution. Several pieces of each testis were embedded in paraffin and processed for immunohistochemical and stereological analysis. All investigated testes have shown sex cords in the process of development and differentiation. Morphologically, peritubular cells in the lamina propria can be divided into two types: fibroblast-like (FL) and myoid-like (ML) type (cells which much resemble mature myoid cells). By immunohistochemistry, both FL and ML cells are found to be strongly positive for the intermediate filament desmin, but negative for -smooth actin. While FL cells intensively express Ki-67 demonstrating proliferative activity, ML cells are found to be negative. The basement membrane of sex cords as well as the blood vessels of the interstitium show strong positivity to collagen IV and laminin. Concerning the correlation between the appearance of the investigated antigens with the gestational age, all antigens have been expressed (in the manner described above) already in the 14th week of gestation. The stereological analysis of the number (Nv) and volume (Vv) of peritubular cells indicates a pulsatile development of these cells in the lamina propria of the human fetal testis. While the stereological variables determined for FL cells show a gradual decrease, the same variables determined for ML cells demonstrate a successive increase. It appears that the lamina propria of the fetal human testes shares many of the properties previously discovered in rodents.     

The oligosaccharidic content of the glycoconjugates of the prepubertal descended and undescended testis: lectin histochemical study

The saccharidic content of the glycoconjugates has been studied in the descended the undescended testes of a 8 years old boy. For this purpose, a battery of seven HRP-conjugated lectins (SBA, DBA,PNA,WGA,UEAI, LTA and ConA) was used. D-galactose-N-acetyl-D-galactosamine and alpha-L-fucose sugar residues, which were present in the cytoplasm of the Sertoli cells of the normally positioned prepubertal testis, were not detected in the same cells of the undescended testis. The Leydig's cells of the descended testis appeared characterized by N-acetyl-D-glucosamine which was absent in the rare and atrophic Leydig's cells of the cryptorchid testis. Differences in sugar residues distribution between the descended and the undescended testis were also detected in the lamina propria of the seminiferous tubules. Peritubular myoid cells in the undescended testis only reacted with PNA, after neuraminidase digestion, thus revealing the presence of D-galactose (beta1-->3)-N-acetyl-D-galactosamine and sialic acid. In this study a complete distributional map of the sugar residues of the glycoconjugates in the descended and undescended prepubertal testis is reported.     

Case report of rat true hermaphroditism: colocalization of oocytes and granulosa and sertoli cells in the germinal cord

We describe a case of rat hermaphroditism with bilateral ovotestes. In a 7-week-old apparently male Sprague-Dawley rat, both testes were relatively small, and the right testis with a faint protrusion was somewhat round and small as compared with the left testis. Microscopically, the testes contained ovarian tissues within their tunica albugineas in conjunction with spermatogenesis in the seminiferous tubules. As bilateral changes, oocytes surrounded by granulosa-like cells were present in the seminiferous tubule-like germinal cord. Granulosa-like and Sertoli-like cells were layered together on the basal lamina, and theca interna-like cells were occasionally observed around the basal lamina. As unilateral changes, cystic dilatation of the germinal cords with eosinophilic fluid was seen in the lumen, and the theca interna-like cells appeared to be vacuolated. Immunohistochemically, the granulosa-like and Sertoli-like cells showed positive reactions for 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and vimentin, respectively. Theca interna-like cells reacted positively to both 3beta-HSD and cytochrome P-450 17alpha-hydroxylase. Ultrastructurally, the granulosa, Sertoli, and theca interna cells were also identified in the ovarian tissue. From these morphological characteristics, the male rat with bilateral ovotestes was diagnosed as true hermaphroditism.     

The peritubular myofibroblasts in the testes from normal men and men with Klinefelter's syndrome. A quantitative, ultrastructural, and immunohistochemical study.

The ultrastructure and immunostaining with antibodies against actin, desmin, and vimentin were studied in the peritubular myofibroblasts of testes from normal men and men with Klinefelter' syndrome (KS). The seminiferous tubules were classified into five types (a-e), related to the progressive degree of sclerosis measured as thickening of the lamina propria. In control testes, only types a and b tubules were present, whereas the testes from men with KS showed types b, c, d, and e tubules. The ultrastructural study revealed abundant microfilament bundles with electron-dense bodies in the cell periphery of the myofibroblasts in a and b tubules. In c tubules, the microfilament bundles of the myofibroblasts were lacking in electron-dense bodies. Myofibroblasts in tubules d and e showed scanty microfilament bundles. Immunostaining of peritubular myofibroblasts with anti-actin antibodies was intense in tubule types a-c and scanty in types d and e. Immunostaining of myofibroblasts with anti-desmin antibodies was intense in tubule types a and b, and negative in types c-e. Immunostaining with anti-vimentin antibodies was weak in tubule types a-c and intense in types d and e. Quantitative study revealed that with the progression of sclerosis, the number and volume per cross-sectioned tubule of actin-containing cells and, mainly, desmin-containing cells decrease while the number and volume of vimentin-containing cells increase.     

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 profiles of cryptorchid XXY mouse testes

Two mice with an XXY karyotype and cryptorchid testes appeared spontaneously in a colony. The animals were H-Y antigen-positive, and had elevated serum levels of follicle-stimulating (FSH) and luteinizing (LH) hormones. Testes of the affected mice were atrophic, containing a few solid seminiferous cords surrounded by vast amounts of compact interstitial material. The cords were delimited by a broad tunica propria in which the basal lamina was irregularly thickened and stratified into a number of alternating dense and less dense layers. Most sex cords were populated by mature Sertoli cells and small pleomorphic elements resembling monocytic-derived macrophages. Within some cords, the macrophages aggregated into a central mass with which identifiable Sertoli cells and (PAS) periodic acid Schiff-positive fragments of basal lamina were associated. In more severely damaged cords, the basal lamina and peripheral carpet of Sertoli cells were totally missing. Such cords were populated only by the central macrophages with fragments of basal lamina and degenerating Sertoli cells. Finally, a few collapsed remnants of cords contained compact nodules of macrophages surrounded by what appeared to be the outer part of the tunica propria. The interstitial area, as well as the outer walls of the seminiferous cords were also heavily infiltrated by macrophages. Overall, the morphological picture was one of severe immunological injury. We do not know what role, if any, the genetic constitution and/or intra-abdominal environment may play in the expression of these bizarre pathologies. However, such severe changes have not been reported in either Klinefelter's syndrome or the undescended testes of any human or subprimate species.     

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.     

应激猪睾丸葡萄糖转运蛋白1和葡萄糖转运蛋白2的表达与定位

目的 探讨正常和热应激条件下,葡萄糖转运蛋白1（GLUT1）和葡萄糖转运蛋白2（GLUT2）在成年猪睾丸的表达和定位。 方法 性成熟长白公猪9头,随机分为3组。局部阴囊热刺激组（n=3）,用自制电热毯置阴囊42 ℃加热1 h;环境热应激组（n=3）,每天置于37～40 ℃猪舍环境3 h,连续7 d,每天于热处理结束后,将实验猪驱赶回21～25 ℃猪舍环境;对照组（n=3）,饲养在21～25 ℃猪舍环境。局部热刺激6 h后和环境热应激处理结束24 h后,手术摘除双侧睾丸。用Real-time PCR、Western blotting和免疫组织化学技术检测猪睾丸组织内GLUT1和GLUT2的表达。 结果 Real-time PCR和Western blotting结果显示,与对照组相比,环境热应激组GLUT1蛋白和mRNA的表达差异不显著,局部阴囊热刺激组GLUT1蛋白和mRNA表达显著升高;环境热应激组和局部阴囊热刺激组,GLUT2蛋白和mRNA表达均显著升高。免疫组织化学结果发现,热处理前后,GLUT1蛋白在曲精小管内定位于精母细胞和圆形精子细胞;环境热应激组GLUT1蛋白染色与对照组相比,无明显差异,局部阴囊热刺激后,GLUT1染色变深,表达升高。热处理前后,GLUT2蛋白在曲精小管定位于生精细胞和支持细胞,环境热应激和局部阴囊热刺激导致GLUT2染色变深,表达升高。 结论 葡萄糖转运蛋白GLUT1和GLUT2表达于猪睾丸曲精小管,环境高温和阴囊局部热刺激导致GLUT1和GLUT2在猪睾丸的表达水平改变,提示这两种葡萄糖转运蛋白在猪精子发生过程中发挥重要作用。     

The vanishing testis: a histomorphologic and clinical assessment

Of patients with cryptorchidism, 5% have no palpable gonad. Physical examination or scrotal exploration demonstrates tissue nubbins or small nodules that constitute the vanishing testis syndrome. At the University of Chicago Hospitals (Chicago, IL; 2004-2008), 30 surgical pathology specimens from 29 patients with this clinical diagnosis underwent scrotal exploration. Histologic and immunohistochemical comparison was done with 7 fetal testes, 8 surgically removed nonneoplastic testes, and 2 cryptorchid testes. Routine histologic studies showed no seminiferous tubules in 18 cases (60%), fibrosis in all (100%), calcifications in 16 (53%), and hemosiderin deposits in 9 (30%). In 12 cases with seminiferous tubules (40%), there were Sertoli cells only. Scrotal exploration in such cases is clinically driven and results in the removal of any tissue present. Although published studies suggest the risk for future tumor development is low, possibly absent, the definitive removal of a testicle is established by an awareness of the histologic spectrum exhibited by testicular remnants.     

Leydig cells within the aspermatogenic seminiferous tubules

Cells identical to Leydig cells were found within a peritubular boundary layer and even inside a basal lamina of seminiferous tubules in three male patients (two with inguinal cryptorchism and one with infertility). The seminiferous tubules of all patients showed a moderate to marked thickening of the boundary layer and a complete loss of spermatogenic cells. The "ectopic Leydig cells" were characterized by the presence of Reinke crystals or an extensively developed smooth endoplasmic reticulum. These cells were believed to have differentiated in situ from myoid cells within the boundary layer and also to have invaded from the interstitial tissue in the form of mature Leydig cells. The occurrence of ectopic Leydig cells appeared to parallel the extent of loss of the Sertoli cells and also that of the thickening of the boundary layer. The functional significance of the ectopic occurrence might be implicated in the impaired spermatogenesis.     

The peritubular myoid cells in the testes from men with varicocele: an ultrastructural, immunohistochemical and quantitative study

Ultrastructural and some immunophenotypic features of the peritubular myoid cells of testes from normal men and from men with varicocele were studied. The seminiferous tubules were classified into five types (a-e), related to the progressive degree of sclerosis measured as thickening of the lamina propria. In normal testes only type a and b tubules were found, whereas the testes from men with varicocele showed type b-e tubules. Myoid cells in tubule types a and b showed slender cytoplasmic projections with abundant, parallel arranged microfilament bundles and electron-dense bodies. In c tubules, the myoid cells showed the same ultrastructure. The myoid cells of tubules with advanced (type d) or complete (type e) sclerosis showed irregularly outlined nuclei, scant microfilament bundles and absence of electron-dense bodies. Immunostaining of myoid cells with anti-actin antibodies was intense in types a-c tubules and scant in types d and e. Immunostaining with anti-desmin antibodies was intense in tubules types a-d, but the immunoreactive cells in types c and d tubules were irregularly shaped and distributed and were scanty in tubule type e. Immunostaining with anti-vimentin antibodies was weak in types a-c tubules and intense in types d and e tubules. Quantitative studies revealed that, with the progression of sclerosis, the numbers of both actin- and desmin-immunoreactive cells per cross-sectioned tubule, and the surface area occupied by the immunostained portion of these cells, decreases while the number of vimentin-immunoreactive cells and their immunostained surface area increases.     

Endothelin and endothelin receptors A and B in the human testis

 Human testicular capillaries interconnect Leydig cells and seminiferous tubules. Microcirculation and blood flow are therefore essential for the maintenance of spermatogenesis. The expression and the localisation of ET (endothelin) and its receptors in testicular tissue, in seminiferous tubules and in human testicular capillaries were studied. ET-1 mRNA was detected in whole testicular tissue and in seminiferous tubules whereas isolated testicular capillaries were negative. Big ET-1 (Big endothelin 1) and ET peptides were localised in Leydig and Sertoli cells whereas interstitial and intramural capillaries (within the lamina propria) remained unstained. ET was also found in mature spermatids. ET-A (endothelin receptor A) mRNA was detected in seminiferous tubules and whole testicular tissue whereas testicular blood vessels were negative. ET-A immunostaining was displayed in Leydig and Sertoli cells and in spermatids. ET-B (endothelin receptor B) mRNA was detected in whole testicular tissue, seminiferous tubules and in testicular capillaries. ET-B peptide was prominent in Leydig cells, peritubular cells, endothelial cells and pericytes of interstitial and intramural capillaries as well as in vascular endothelial and smooth muscle cells. From these results we conclude that ET produced in Leydig and Sertoli cells can act in a paracrine manner via ET-B on the human testicular microvasculature and the peritubular cells. The presence of both ET-A and ET-B in Leydig cells and of ET-A in Sertoli cells leads to the assumption that ET could influence these cells as an autocrine factor. Accepted: 9 October 1998     

The fine structure and development of the peritubular contractile cell component in the seminiferous tubules of the mouse

Testes of sexually mature, as well as newborn and young mice of varying ages were studied by electron microscopy. The seminiferous tubules in the mature mouse possess a single cell layer of extremely flattened cells which form a sheath-like structure around the epithelium of the tubule. These peritubular cells are characterized by cytoplasmic filaments and other features which are typical of smooth muscle cells. A basement lamina is associated with the interstitial or peripheral surface of the cell. Peripherally, there is an additional cellular layer consisting of connective tissue fibrocytes. In newborn animals, the cells surrounding the tubule epithelium consist of a homogeneous population of fibroblasts, 3–4 layers in thickness. With growth and development of the testes the number of cell layers is reduced and the cells become more attenuated. At 13 days, those cells which are closest to the epithelium show localized aggregates of fine filaments, as well as what appears to be the elaboration of a basement lamina. By 17 days, the cytoplasmic filaments are more numerous and the basement lamina is well defined: by 19 days, the cells closely resemble the peritubular muscle cells of the adult. The probable functional role of these cells is discussed with respect to both sperm transport and the production and maintenance of the surrounding connective tissue stroma.     

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.     

Human 'testicular dysgenesis syndrome': a possible model using in-utero exposure of the rat to dibutyl phthalate

BACKGROUND: The disorders comprising human 'testicular dysgenesis syndrome' (TDS) may be increasing in incidence. TDS originates in fetal life but the mechanisms are not known, and discerning them requires an animal model. METHODS AND RESULTS: The study investigated whether male rats exposed in utero to dibutyl phthalate [DBP; 500 mg/kg on gestational days (GD) 13-21] would provide a suitable model for human TDS. DBP induced a high rate (>60%) of cryptorchidism (mainly unilateral), hypospadias, infertility and testis abnormalities, similar to those in human TDS. Cell-specific immunohistochemistry and confocal microscopy were used to track development of Sertoli [anti-Müllerian hormone (AMH), Wilm's tumour (WT-1) protein, p27(kip)], Leydig [3beta-hydroxysteroid dehydrogenase (3beta-HSD)], germ (DAZL protein) and peritubular myoid (smooth muscle actin) cells from fetal life to adulthood. In scrotal and cryptorchid testes of DBP-exposed males, areas of focal dysgenesis were found that contained Sertoli and Leydig cells, and gonocytes and partially formed testicular cords; these dysgenetic areas were associated with Leydig cell hyperplasia at all ages. Suppression ( approximately 90%) of testicular testosterone levels on GD 19 in DBP-exposed males, coincident with delayed peritubular myoid cell differentiation, may have contributed to the dysgenesis. Double immunohistochemistry using WT-1 (expressed in all Sertoli cells) and p27(kip) (expressed only in mature Sertoli cells) revealed immature Sertoli cells in dysgenetic areas. DBP-exposed animals also exhibited Sertoli cell-only (SCO) tubules, sporadically in scrotal and predominantly in cryptorchid, testes, or foci of SCO within normal tubules in scrotal testes. In all SCO areas the Sertoli cells were immature. Intratubular Leydig cells were evident in DBP-exposed animals and, where these occurred, Sertoli cells were immature and spermatogenesis was absent. Abnormal Sertoli cell-gonocyte interaction was evident at GD 19 in DBP-exposed rats coincident with appearance of multinucleated gonocytes, although these disappeared by postnatal day 10 during widespread loss of germ cells. CONCLUSIONS: Abnormal development of Sertoli cells, leading to abnormalities in other cell types, is our hypothesized explanation for the abnormal changes in DBP-exposed animals. As the testicular and other changes in DBP-exposed rats have all been reported in human TDS, DBP exposure in utero may provide a useful model for defining the cellular pathways in TDS.     

人与几种常用啮齿动物曲细精管周组织超微结构及碱性磷酸酶电镜细胞化学的定位

本文对人、兔、豚鼠、大鼠及小鼠的曲细精管周组织的超微结构和碱性磷酸酶(AIP)定位进行了观察。人的曲细精管周组织内一般有3层细胞,有细长分支突起,最内层呈肌样细胞特征,向外层的细胞则与成纤维细胞相似。相邻肌样细胞之间多见较宽的细胞间隙。AIP 位于基板、最内侧胶原原纤维区、肌样细胞胞质和向内侧质膜。4种啮齿动物曲细精管周组织微细结构基本相似,但也有某些区别。兔与豚鼠的单层肌样细胞的相邻末端可重叠排列呈2层,而大鼠和小鼠的肌样细胞则呈单层包绕。兔的基板为1～2层,其它3种动物只有1层。4种动物的相邻肌样细胞之间皆有紧密连接与宽度为100～200(?) 的开放间隙,以及更宽的细胞间隙。这4种动物的基板、内非细胞层、肌样细胞胞质及其向内侧质膜和淋巴窦内皮细胞皆有 AIP 分布,除兔以外,豚鼠、大鼠和小鼠的肌样细胞外侧质膜和外非细胞层也有 AIP 分布。本文讨论了曲细精管周组织及 AIP 酶鞘的生理意义。     

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.