Effects of testosterone enanthate on the structure of the male reproductive tract of the rat

The histology and fine structure of the testis, epididymis and sex accessory glands were studied in young adult male rats administered testosterone enanthate, 120 μg/100 g body weight, three times weekly for 4, 8, or 12 weeks. The weights of the testis and epididymis decreased, and animals treated for 11 weeks were infertile. Alterations were found in the seminiferous tubules of all rats treated for 8 or 12 weeks, including the presence of many degenerating germ cells and a-large decrease or absence of late spermatids. Study of different stages of the cycle of the seminiferous epithelium showed that the greatest number of degenerating germ cells, step 7 spermatids and pachytene primary spermatocytes, occurred at stages VII-VIII of the cycle. Some normal appearing spermatogonia, primary spermatocytes and early spermatids remained in most seminiferous tubules. Sertoli cells contained many lipid droplets and lysosome-like bodies, and degenerating cells were surrounded by Ser-toli cell cytoplasm. The Leydig cells of treated animals were greatly reduced in size. Sperm progressively disappeared from the lumen of the middle segment and proximal part of the terminal segment of the epididymis after treatment for 8 or 12 weeks. Changes in the middle segment also included the appearance of intraepithelial cavities containing debris, and the presence within the epithelium of phagocytic cells that resembled leukocytes. The lumen of the proximal part of the terminal segment was often collapsed, while in the distal part of the terminal segment, the lumen was filled with cellular debris and degenerating sperm. Organelles of the principal cells of the epididymal epithelium appeared to be qualitatively unaltered. The weight of the sex accessory glands remained close to normal, and the presence of normal ultrastructural features suggested that production of secretions continued.     

大鼠睾丸和附睾中钙调素免疫组织化学定位的研究

用免疫组织化学ＡＢＣ法，观察了钙调素在大鼠睾丸和附睾的定位与分布。结果表明，钙调素免疫反应产物分布在精母细胞，精子细胞和精子中，而精原细胞，Ｓｅｒｔｏｌｉ细胞和Ｌｅｙｄｉｇ细胞呈阴性反应。钙调素免疫反应既见于胞质中，也见于胞核中。相邻曲细精管钙调素免疫反庆强度呈明显的不均一性。不同发生阶段的生精细胞间免疫反应强度也存在差异。大附睾，钙调素免疫反应见于附睾管尾段主细胞顶端胞质内，偶见于主细胞的基底部     

不同阶段生精小管组织学结构研究

目的探讨不同阶段人体睾丸生精小管面积、生精小管管腔面积变化和生精上皮在不同阶段的组织学特点,及其与生殖的关系。方法:应用常规组织制片技术和图像分析技术。结果①生精小管平均面积变化,从胚胎睾丸形成到青春期前,随睾丸逐渐发育增大,睾丸间质增多,但生精小管面积无明显增大;自青春期生精小管面积迅速增大,25岁左右达到峰值,45岁左右生精小管平均面积缓慢减少,55岁以后显著减少。②生精小管管腔面积变化,从胚胎睾丸形成到青春期前,生精小管几乎无管腔;青春期管腔开始出现并迅速增大,20岁左右达到峰值;于45岁左右管腔面积缓慢减少,55岁以后显著减少。③生精小管的组织学结构变化,从胚胎睾丸形成到青春期前,生精小管上皮由精原细胞和支持细胞组成,但随睾丸发育增大,睾丸间质增多,生精小管上皮和基膜间渐出现明显的间隙;青春期开始,生精小管上皮发育,生精细胞层数增加,管壁各级生精细胞典型,腔面可见精子;55岁后睾丸纤维化明显,生精小管皱缩,随年龄增长,生精上皮细胞数量渐减少,排列紊乱,基膜增厚。结论①生精细胞增殖旺盛是生精小管平均面积迅速增大的原因之一;生精细胞增殖旺盛的阶段是20～30岁,最佳时期是25岁左右。②生精小管管腔的出现与生精细胞的凋亡、基膜扩大的速率远远大于生精细胞的增殖水平有关,而生精小管管腔的出现有利于精子的生成与运输。③衰老睾丸生殖功能的下降与其组织结构的纤维化及生精小管基膜厚度增加等因素有关。     

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.     

The initial segment of the rat epididymis is able to uptake immature germ cells shed by testicular damage

The initial segment of the caput epididymidis, the most proximal part of the rat epididymis, has specific functional characteristics. In the present study, the behavior of the epididymal epithelium from this region was evaluated after the exposure to a massive number of immature germ cells in the luminal fluid. The experimental release of immature germ cells from the seminiferous tubules was performed by injecting anti-microtubule compounds into the rete testis and the lumen of seminiferous tubules. Twenty-four hours after nocodazole or colchicine administration, a massive phagocytosis of immature spermatogenic cells, recognized as acrosin-positive structures, was easily observed in the epithelium of the initial segment of the epididymis assessed by light and electron microscopy. Immature germ cells were engulfed by epithelial cells, where most of them were found as cell debris at different stages of degradation. No signs of inflammation were observed either in the lumen or in the interstitium. The phagocytosis of immature germ cells was restricted to the epithelium of the initial segment of the epididymis, suggesting a role for this segment as the first selective barrier for the exclusion of abnormal gametes along the male genital tract.     

Stage-specific expression of mouse germ cell-less-1 (mGCL-1), and multiple deformations during mgcl-1 deficient spermatogenesis leading to reduced fertility

A mouse homologue of Drosophila germ cell-less, mouse germ cell-less-1 (mgcl-1), is highly expressed in the testis. Previous report revealed that the fertility of the mgcl-1(-/-) male mice is reduced significantly as a result of various morphological abnormalities in the sperm (Kimura et al., 2003). To elucidate the function of mgcl-1 in spermatogenesis, the expression of mGCL-1 in the wild-type testis was examined. Immunohistochemical studies demonstrated that mGCL-1 first appeared in the nuclei of the pachytene spermatocytes at stage VI of the seminiferous epithelium, and existed in those of spermatids until step 8 during spermatogenesis. mGCL-1 was not detectable after step 9 spermatids. The testicular cells and epididymal sperm were further analyzed morphologically using mgcl-1(-/-) mice. In the testis, deformed nuclei first occurred in the pachytene spermatocytes at stage VI, which is consistent with the time of the first appearance of the mGCL-1 protein in the wild-type testis. Abnormal nuclei and acrosomes were found in spermatids after step 5, and nuclei of the spermatids and epididymal sperm were frequently invaginated. In addition, variously deformed sperm such as bent-neck, multi-headed or multi-nucleated sperm were observed in the mgcl-1(-/-) cauda epididymidis. However, several key structures such as the acroplaxome marginal ring (Kierszenbaum et al., 2003), postacrosomal sheath, and posterior ring apparently formed. In addition, MN7 and MN13, essential substances for fertilization that are located in sperm heads, were detectable in the mgcl-1 null sperm. These observations provide important insights into the mechanisms regulating the nuclear architecture and causes of human infertility.     

Development and Morphogenesis of Testis in Human Fetuses

Development and maturation of prenatal testis was studied on 104 human male fetuses. At 9 weeks, the testes were seen as elongated yellowish tissue superolateral to the developing urinary bladder and medial to mesonephros. The testis assumed ellipsoidal shape at 13 weeks. At about 16 weeks, the testes developed convexity on its anterior aspect. Epididymis and testis were at the same level until 20 weeks thereafter the upper testicular pole was encroached upon by the epididymis, with complete encroachment till its anterior aspect at 24 week. The sinus was also distinctly present between the two. The testis assumed miniature adult testis at term, but its size was approximately 1/15th of the adult. Cytoarchitecture of the testis at 9 weeks revealed radially disposed sex cords. At 13 weeks, tunica albuginea,tubular organization in the parenchyma and the Leydig cells were identifiable. At 17 weeks, tunica vasculosa and incomplete lobules were apparent. At 24 weeks, testis was marked by more but solid seminiferous tubules lined by 4–5 germ layers. Leydig cells were also identifiable till 24 weeks. Spermatogenic cells, both pale and dark type were distinguishable although pale spermatogonia were more numerous than dark cells. 28 weeks onwards tunica vaginalis and complete septa in the testicular parenchyma were evident. Moreover, the seminiferous tubules developed central vacuolation. By 30 weeks, seminiferous tubules became more complex as evident by their increase in number and coiled and tortuousity. At term, the fetal testis had not yet attained the cytoarchitecture of the adult testis suggesting that testicular maturation continues postnatally.     

Induction of experimental autoimmune orchitis in guinea pigs after ligation of the seminiferous ducts

In 18 immature guinea pigs both sides of the vasa efferentia were ligated; 18 control animals were not altered. The ligation did not prevent the formation in mature animals of active spermatogenesis in the majority of seminiferous tubules, but did cause a reduction in the number of layers of seminiferous epithelium in some, and atrophy of the epididymis due to the absence of germ cells. Immunization, in the adult stage, with homogenate of homologous testis mixed with complete Freund adjuvant created changes in the permeability of the blood-testis barrier in relation to endogenous globulins and rivanol and the development of autoimmune orchitis of the same intensity and terms as in the control animals. In contrast to the control group, destructive changes in the testis did not follow with inflammatory processes in the epididymis.     

Seminiferous tubule stages in the prairie dog (Cynomys ludovicianus) during the annual breeding cycle

The male prairie dog (Cynomys ludovicianus) is an annual breeder with complete testicular regression between breeding periods. Knowledge of the seminiferous tubule cycle stages at all phases of the annual cycle is essential for evaluation of testicular effects of endogenous and exogenous hormones. Testis tubule diameter is directly correlated with testicular weight during the annual cycle. Seminiferous tubule stages found during testicular activity start with sperm release and round spermatids in the Golgi stage (I). Then they progress through the cap and acrosome stages (stages II to VI) until elongate spermatids are formed. During these stages preleptotene, leptotene and zygotene cells develop into pachytene cells which mature with the long spermatids (stage VII). Two distinct tubule associations (stages VIII, IX) follow during which the first and second meiotic metaphases occur. These stages are correlated with the middle and late phases of residual lobe retraction and condensation. The last stage (X) has final sperm development and is present with round spermatids that have no Golgi development. During regression changes are initially associated with the seminiferous tubule stages of active testes and end with relocation of Sertoli cell nuclei to a position above the basal layer of spermatogonia. Out of season testes are characterized by few spermatogonial mitoses and absence of viable spermatocytes. In recrudescent testes, Sertoli cell nuclei again become basal, spermatogonia resume mitoses and spermatocytes and spermatids progressively develop. After each cycle of proliferation of germ cells there is sloughing of the most differentiated spermatocytes and spermatids until the final tubule associations of the active testis are present. Anat. Rec. 247:355–367, 1997. © 1997 Wiley-Liss, Inc.     

Experimental allergic orchitis in mice

Summary Experimental allergic orchids was induced in (C57BL/6J × A/J)F₁ mice by two injections of syngeneic testicular homogenate emulsified with adjuvants immediately followed by intravenous injection of pertussis vaccine, at a 2 week interval.Histologically, in the initial stage there was occasional focal degeneration and desquamation of both spermatogonia and Sertoli cells within limited parts of the seminiferous tubules, in the peripheral region of the testis. No inflammatory change was present. In some cases, however, inflammatory reaction in the rete testis and focal lymphocytic infiltration in the interstitium were also observed. Subsequently, marked infiltration of lymphocytes, monocytes, and polymorphs were found not only in the testes, but also in rete testis and epididymis. In later stages the inflammatory reaction gradually subsided, but the testes became atrophic due to progression of spermatogenic arrest. Many tubules were lined only with monolayers of Sertoli cells, surrounded by hyperplastic Leydig cells in the interstitium. At 5 months after the 2nd immunization, there was still variable depression of spermatogenesis and hyperplasia of Leydig cells with scattered fibrous scars in the seminiferous tubules, although good regeneration of germ cells appeared in some tubules.Immunological studies revealed that lymphocytes obtained from mice bearing developed orchitis showed a significantly enhanced response in the mixed culture with syngeneic testicular cells, and suggest that cellular immunity plays an important role in the induction of experimental allergic orchitis in mice.     

Testis structure, spermatogenesis, spermatocytogenesis, and sperm structure in cardinal fish (Apogonidae, Perciformes)

The testes in all 16 of the studied cardinal fish species are shown to be bilobed, with spermatogonia dispersed throughout the gametogenic epithelium of the seminiferous tubules. Each testicular lobe is covered luminally by an epithelium consisting of primary germ cells and Sertoli cells. At maturation the seminiferous tubules reach around 0.6–2.3 mm in length. They number from 60 in the smallest species to over 300 in the largest one, increasing both in dimension and number with increase in length of the male, and are species-specific. The highest number of spermatogonia is found at the apical ends of the tubules. During maturation extensions of Sertoli cells surround single or small groups of B-spermatogonia, forming the spermatocysts, the final dimensions of which reflect the final number of contained spermatozoids. Back-calculations of serial sections reveal that within the spermatocysts the spermatogonia undergo eight generations of mitotic divisions before the first and second meiotic divisions and formation of spermatids. The largest mature spermatocysts in large species attain around 180 μm in diameter, a volume of 25 mm³, and contain around 8,200 spermatids. The total volume of sperm in the mature spermatocysts leaves enough space for the discarded cytoplasm and developing flagella. The bursting cysts liberate the ripe sperm and maturing spermatids, into the tubule lumen and spermduct, with the spermatids often still connected by cytoplasm bridges. The sperm, with one or two flagella, features round or oval heads and a cytoplasmic collar bearing a few mitochondria. The percentage of biflagellate or monoflagellate sperm differs in proportion in males of different lengths and in different species. Differences in spermatogenesis of small and larger species of cardinal fish are discussed.     

昆明山海棠抗生育作用的形态学研究：Ⅰ.睾丸,附睾的组织化学观察

本文应用组织化学方法探讨昆明山海棠(TH)对雄性大鼠睾丸,附睾的DNA、RNA.乳酸脱氢酶(LDH)、琥珀酸脱氢酶(SDH)、ATP酶,葡萄糖-6-磷酸脱氢酶(G-6PDH)等的影响。成年雄性SD大鼠用昆明山海棠根50%乙醇提取物灌胃给药,剂量1.0g/kg/日,每周六次,共6周,所有用药鼠均丧失生育力。用药鼠附睾管腔内精子减少或完全消失,并可见少量脱落和退化的生精细胞(主要是精子细胞)。附睾头、尾部管腔内精子大部分呈断头、卷尾等畸形。精子LDH.SDH活性明显下降。精子细胞及残余体RNA凝集成块,而精原细胞、精母细胞,支持和间质细胞及附睾各段上皮细胞的形态和组织化学均未见明显改变。本实验表明,TH主要影响精子细胞RNA的功能及精子糖代谢,而对其它生精细胞无明显作用。     

Morphometric studies on rat seminiferous tubules

The goal of this morphometric study was to obtain quantitative information on the seminiferous tubules of Sprague-Dawley rats, including changes seen at various stages of the cycle of the seminiferous epithelium. Tissue from perfusion-fixed testes was embedded in Epon-Araldite; and sections were subjected to morphometric measurements at the light microscopic level, using point counting for volume densities and the Floderus equation for numerical densities. Changes occur in the diameter of the seminiferous tubule, as well as in the volume of the seminiferous epithelium and tubule lumen, from stage to stage during the cycle. A significant constriction of the seminiferous tubule accompanies spermiation. The volume of the seminiferous epithelium per unit length of the tubule begins to increase after stage XIV, and peaks at stage V of the next cycle. The tubule lumen increases dramatically from stages V to VII, at the expense of the epithelium. The number of Sertoli cells is constant per unit length of the seminiferous tubule at all stages of the cycle. This is also true for primary spermatocytes of various developmental phases and for round spermatids from step 1 through step 10 of spermiogenesis. The average number of younger (preleptotene, leptotene, zytgotene) primary spermatocytes per Sertoli cell is 2.34 ± 0.082 (SEM), the number of older (pachytene, diplotene) primary spermatocytes per Sertoli cell is 2.37 ± 0.064, and the ratio of step 1–10 spermatids to Sertoli cells is 7.89 ± 0.27. By studying tangential views of serially sectioned seminiferous tubules at stage V, it is shown that the number of step-17 spermatids associated with each Sertoli cell averages 8.35 ± 0.128, although the counts ranged from 6 to 11. The only appreciable occurrence of cell death after the last spermatogonial mitosis appears to be a 15% loss during the first meiotic division. From our morphometric results, corrected for volume changes during preparation for microscopy, there are 15.7 million (± 0.99 million) Sertoli cells per gram of fresh rat testis. The length of seminiferous tubule per gram of testis is estimated to be 12.4 ± 0.56 meters, and the tubule surface area per gram testis is 119.7 ± 2.57 cm². The daily production of mature spermatids is 9.61 million (± 0.615 million) per gram of testis.     

Ectoplasmic specialization, a testis-specific cell-cell actin-based adherens junction type: is this a potential target for male contraceptive development?

The seminiferous tubule of the mammalian testis is largely composed of Sertoli and germ cells, which coordinate with Leydig cells in the interstitium and perform two major physiological functions, namely spermatogenesis and steroidogenesis respectively. Each tubule is morphologically divided into (i) the seminiferous epithelium composing Sertoli and germ cells, and (ii) the basement membrane (a modified form of extracellular matrix); underneath this lies the collagen fibril network, the myoid cell layer, and the lymphatic vessel, which collectively constitute the tunica propia. In the seminiferous epithelium, of rodent testes each type A1 spermatogonium (diploid, 2n) differentiates into 256 elongated spermatids (haploid, 1n) during spermatogenesis. Additionally, developing germ cells must migrate progressively from the basal to the luminal edge of the adluminal compartment so that fully developed spermatids can be released into the lumen at spermiation. Without this timely event of cell movement, spermatogenesis cannot reach completion and infertility will result. Yet developing round elongating/elongated spermatids must remain attached to the epithelium via a specialized Sertoli-germ cell actin-based adherens junction (AJ) type known as ectoplasmic specialization (ES), which is crucial not only for cell attachment but also for spermatid movement and orientation in the epithelium. However, the biochemical composition and molecular architecture of the protein complexes that constitute the ES have only recently been studied. Furthermore, the signalling pathways that regulate ES dynamics are virtually unknown. This review highlights recent advances in these two areas of research. It is expected that, if adequately expanded, these studies should yield new insights into the development of novel contraceptives targeted to perturb ES function in the testis. The potential to specifically target the ES may also mean that contraceptive action could be achieved without perturbing the hypothalamic-pituitary-testicular axis.     

Fine structure of the testis and epididymis of rats treated with cyproterone acetate

Adult male rats were administered the antiandrogen, cyproterone acetate, for 4, 8 or 12 weeks, and the histology and fine structure of the testis and several parts of the epididymis were studied. After treatment for 8 or 12 weeks, the testes of treated animals displayed a great reduction in the abundance of late spermatids. Necrotic cells, many of which were identified as cap-phase spermatids, were present in the seminiferous epithelium. Sertoli cells contained many large lipid droplets and lysosome-like structures with a content of cellular debris, including parts of spermatids. Leydig cells of treated rats were smaller than those of control animals at all the intervals studied. Sperm were absent from the lumen of the middle segment, or caput epididymidis, of severely affected specimens. In the terminal segment, or cauda epididymidis, the microscopic appearance varied in different regions. In the proximal part of the cauda epididymidis, the lumen was usually clear of sperm. The epithelium was tall and the light cells were very large and distended with many dense bodies resembling lysosomes. In contrast, in the distal part of the cauda epididymidis, the lumen was filled with sperm and debris, which appeared to be derived from germ cells. It is suggested that the light cells of the epididymal epithelium may have a role in clearing the lumen in the proximal part of the cauda epididymidis, in which they are particularly large and numerous. The results suggest that in the presence of cyproterone acetate, germ cells develop up to cap-phase spermatids and then begin to undergo degeneration and death. This alteration may have an important role in the antifertility effect of the drug, but changes in the epididymis may contribute also.     

The degenerative fate of germ cells not conforming to stage in the pubertal golden hamster testis

In the golden hamster ( Mesocricetus auratus ), pubertal establishment of spermatogenesis includes a defined period (d 26–30 of life) during which elongation of spermatids is selectively arrested. The resulting appearance of germ cell associations not conforming to stage and the phenomenon of desynchronisation-related germ cell degeneration are analysed both quantitatively and qualitatively by means of light and 'retrospective' electron microscopy. From d 26 onwards, the portion of tubules containing non-stage conforming germ cell associations gradually increases up to 37.5% of sectioned tubules on d 32. Concomitantly, the degree of desynchronisation rises to a maturational gap between spermatids and associated younger germ cells of 7 stages of the seminiferous epithelium cycle, i.e. of fully half a cycle. Beyond d 32, the frequency of desynchronised tubule segments decreases again. Some of the arrested round spermatids and, eventually, all belatedly elongating spermatids degenerate and are lost from the epithelium. Thus a regular maturation of advanced spermatids does not succeed under non-stage conforming conditions. Possibly it is not the desynchronisation between the associated germ cell generations and the spermatids by itself that impedes normal further development of the latter cells. Instead this may be due to the maturational delay of the stage-aberrant cells by several stages compared to the seminiferous epithelium as a whole and, especially, in relation to the stage-conditioned functional state of the neighbouring Sertoli cells.     

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.     

Fas expression correlates with human germ cell degeneration in meiotic and post-meiotic arrest of spermatogenesis

Degeneration of human male germ cells was analysed by means of light (LM) and transmission electron (TEM) microscopy. The frequency of degenerating cells was correlated with that of Fas-expressing germ cells in human testes with normal spermatogenesis (n = 10), complete early maturation arrest (EMA) (n = 10) or incomplete late maturation arrest (LMA; n = 10) of spermatogenesis. LM analysis of testis sections with normal spermatogenesis indicated that degenerating germ cells were localized in the adluminal compartment of the seminiferous epithelium. TEM showed that apoptotic cells were mostly primary spermatocytes and, to a lesser extent, round or early elongating spermatids. Apoptotic germ cells appeared to be eliminated either in the seminiferous lumen or by Sertoli cell phagocytosis. An increased number of degenerating cells was observed in testes with LMA as compared with normal testes and testes with EMA of spermatogenesis (P < 0.001, Wilcoxon's rank sum test). Comparison of these results with those obtained from immunohistochemistry experiments demonstrated a tight correlation between the number of apoptotic cells and the number of Fas-expressing germ cells (P = 0.001, Spearman's rank = 0.69). These findings suggest that altered meiotic and post-meiotic germ cell maturation might be associated with an up-regulation of Fas gene expression capable of triggering apoptotic elimination of defective germ cells.     

Effects of respiratory treatment with N-hexane on rat testis morphology. I. A light microscopic study

Testicular damage was induced in rats by respiratory treatment with n-hexane at a concentration of 5000 ppm. The earliest lesions were observed immediately after 24 hr of continuous treatment, and involved primary spermatocytes from the leptotene to the middle pachitene stages and spermatids at late stages of maturation; at the same time numerous exfoliated, injured germ cells reached the epididymis. After the 24-hr treatment was suspended, damage to the seminiferous epithelium increased for the first 7 days, while the epididymis showed also focal infiltration by inflammatory cells; recovery was completed from Days 14 to 30. Intermittent treatment (16 hr/day, 6 days/week) at the same concentration of 5000 ppm for up to 6 weeks induced progressive increases in testicular and epididymal lesions, which, after 5 weeks (when most animals began to show clinical symptoms of polyneuropathy), reached aplasia of the germinal epithelium involving also the spermatogonia. Recovery from clinical symptoms was not paralleled by a regression of testicular pathology. On the contrary, after interruption of the treatment, the testicular lesions became increasingly severe, up to complete atrophy of the seminiferous tubules, suggesting an irreversible sterility of the treated animals. Pair-fed controls did not show histological alterations of the testis or epididymis.