Testicular dysgenesis does not affect expression of anti-müllerian hormone by Sertoli cells in premeiotic seminiferous tubules.

Anti-Müllerian hormone (AMH) immunoreactivity was studied on paraffin sections obtained from archival testicular biopsies of 29 children with intersex disorders and of 22 controls. Strong AMH immunoreactivity was observed in Sertoli cell cytoplasm from 8 fetal weeks until puberty. During pubertal maturation, in both normal and intersex patients, AMH expression was present in premeiotic seminiferous tubules, but was no longer detected in neighboring tubules with meiotic development. AMH immunostaining was abolished in the testis of one patient with persistent Müllerian ducts due to a mutation of the AMH gene, but was conserved in the testes of two patients with mutations of the AMH receptor gene. Testicular dysgenesis usually results in sexual ambiguity, with low testosterone and AMH serum levels and persistence of Müllerian derivatives. AMH immunoreactivity was conserved in premeiotic seminiferous tubules of dysgenetic testes, and also in sex-cord cells of a gonadoblastoma. In patients with asymmetric gonadal differentiation, the streak gonad was AMH-negative. In conclusion, secretion of AMH is a constitutive feature of the immature Sertoli cell and its expression is altered only by mutations of the AMH gene, but not by gonadal dysgenesis. The degree of regression of Müllerian ducts and serum AMH levels reflect the number, not the functional value, of Sertoli cells present in the immature testis.     

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.     

Fate of bone marrow stem cells transplanted into the testis: potential implication for men with testicular failure

To assess adult stem cell differentiation in the testis, we injected bone marrow cells from adult green fluorescent protein (GFP) transgenic mice into the seminiferous tubules and the testicular interstitium of busulfan-treated wild-type or c-kit mutant (W/W(v)) mice. Ten to 12 weeks after transplantation, we examined the fate of the transplanted bone marrow cells and found that they survived in recipient testes. In both the busulfan-treated and W/W(v) mice, some of the GFP-positive donor cells had a Sertoli cell appearance and expressed follicle-stimulating hormone receptor within the seminiferous tubules. In addition, GFP-positive donor cells were found in the interstitium of recipient testes, and they expressed the cytochrome P450 side chain cleavage enzyme (P450scc). In the seminiferous tubules of busulfan-treated mice, GFP-positive donor cells had the appearance of spermatogonia or spermatocytes and expressed VASA. However, this was not found in the seminiferous tubules of W/W(v) mice. We conclude that adult bone marrow cells, in a favorable testicular environment, differentiate into somatic and germ cell lineages. The resident neighboring cells in the recipient testis may control site-appropriate stem cell differentiation. This clinically relevant finding raises the possibility for treatment of male infertility and testosterone deficiency through the therapeutic use of stem cells.     

Orchitis and human immunodeficiency virus type 1 infected cells in reproductive tissues from men with the acquired immune deficiency syndrome.

Mechanisms underlying human immunodeficiency virus type 1 (HIV-1) infection of the male reproductive tract and the sexual transmission of HIV-1 through semen are poorly understood. To address these issues, the authors performed morphologic and immunocytochemical analyses of reproductive tissues obtained at autopsy from 43 male acquired immune deficiency syndrome (AIDS) patients. Monoclonal antibodies recognizing different subpopulations of white blood cells were used to detect leukocyte infiltration and map the location of potential lymphocytic/monocytic HIV-1 host cells and immunocytochemistry and in situ hybridization techniques were used to detect HIV-1-infected cells in the testis, excurrent ducts, and prostate. Distinct pathologic changes were observed in a majority of testes of AIDS patients that included azoospermia, hyalinization of the boundary wall of seminiferous tubules, and lymphocytic infiltration of the interstitium. The reproductive excurrent ducts and prostate appeared morphologically normal except for the presence of focal accumulations of white blood cells in the connective tissue stroma. In the testis many white blood cells were shown to be CD4+, indicating the presence of abundant host cells (T-helper/inducer lymphocytes and macrophages) for HIV-1. Furthermore macrophages and cells of lymphocytic morphology were observed migrating across the boundary walls of hyalinized seminiferous in tubules to enter the lumen. In 9 of the 23 cases tested for HIV-1 protein expression by immunocytochemistry. HIV-1 + cells of lymphocytic/monocytic morphology were found in the seminiferous tubules and interstitium of the testis, epididymal epithelium, and connective tissue of the epididymis and prostate. One patient with epididymal blockage had accumulations of HIV-1-antigen-positive cells of macrophages morphology in the distended lumen of the efferent ducts. There was no evidence of active HIV-1 infection in germ cells or Sertoli cells of the seminiferous tubules or other epithelial cells lining the excurrent ducts or prostatic glands.     

Testicular development in cynomolgus monkeys

The testes from 136 male cynomolgus monkeys were examined histopathologically in order to investigate the relationship between the development of spermatogenesis and testis weight, age, and body weight. At Grade 1 (immature), Sertoli cells and spermatogonia were the only cell classes in the testis. At Grade 2 (pre-puberty), no elongated spermatids were observed in the testis, although a few round spermatids and small lumen formation were observed. At Grade 3 (onset of puberty), all classes of germ cells were observed in the testis, although seminiferous tubule diameters and numbers of germ cells were small. Slight debris in the epididymis was observed in almost all animals. At Grade 4 (puberty), almost complete spermatogenesis was observed in the seminiferous tubules and it was possible to ascertain the spermatogenesis stage as described by Clermont, although tubule diameters and numbers of germ cells were small. There was less debris in the epididymis than at Grade 3. At Grade 5 (early adult), complete spermatogenesis was observed in the seminiferous tubules. At Grade 6 (adult), complete spermatogenesis in the seminiferous tubules and a moderate or large number of sperm in the epididymis were observed. Moreover, sperm analysis using ejaculated sperm was possible. Logistic regression analysis showed that testis weight is a good indicator of testicular maturity.     

Microanatomical study of testis in juvenile ostrich (Struthio camelus)

The majority of investigations on the testis, as the main organ of male reproductive system, have been performed in mammalian species, with few studies on bird species. Thus, the structure of the ostrich testis remains largely unknown. The aim of this study was to investigate the microanatomical characteristics of the testis in five juvenile ostriches. A stereological study was performed according to the Delesse principle. The mean volume fraction of the seminiferous tubules was 0.569, and the mean volume of the seminiferous tubules in an average testis was 1.04 cm³. The Paraffin-embedded sections were stained with hematoxylin and eosin, Masson’s trichrome, Alcian blue, and periodic acid–Schiff stains. Histological studies revealed that the spermatogonial stem cells and Sertoli cells were localized inside the seminiferous tubules, close to the basement membrane. Inside the tubules a few meiotic cells up to the spermatozoa stage were located in a centripetal manner. Outside the tubules, one to three layers of euchromatic peritubular myoid cells were present, surrounded by loose interstitial connective tissue. A thick tunica albuginea contained many myoid cells and some rete ducts, with the latter extending from the hilus to the free surface of the testis. Straight seminiferous tubules were distributed in the lateral surfaces and hilar portions of the capsule but were rare in the free surface. These capsular rete ducts may participate in testicular fluid transit from the distal tubules through the capsule.     

Seasonal changes in spermatogenesis of the Japanese lesser horseshoe bat,Rhinolophus cornutus from a morphological viewpoint

Seasonal changes in spermatogenesis of Japanese lesser horseshoe bats, Rhinolophus cornutus, captured in Aomori Prefecture (Japan) were examined by light microscopy. In March, the seminiferous tubules revealed almost no lumen. The seminiferous epithelium consisted of Sertoli cells and spermatogonia. The interstitium occupied a relatively large area. In June, the seminiferous tubules gradually increased in diameter. Lumen was clearly seen at the center of seminiferous tubules. Mitotic figures of spermatogonia and spermatocytes were occasionally recognized. Interstitium occupation was still abundant. In August, the diameter of seminiferous tubules maximized. The interstitium occupied only a small area. Active spermatogenesis was obvious at this time. Released spermatozoa were frequently observed within the expanded lumen. In October, although spermatogenesis was still active, the diameter of seminiferous tubules tended to decrease in size. In December, active spermatogenesis completely disappeared. The diameter of tubules greatly decreased. In most cases, the seminiferous epithelium contained only Sertoli cells and spermatogonia. Thus, spermatogenesis in Japanese lesser horseshoe bats occurs from the middle or late summer to the middle autumn in Aomori Prefecture. In epididymal tracts, aggregated spermatozoa were recognized throughout the year. The cytoplasm of all Leydig cells in the interstitium was positive for 3beta-hydroxysteroid dehydrogenase throughout the year.     

Encephalomyocarditis (EMC) virus-induced orchitis in Syrian hamsters.

Testes of 8-week-old male Syrian hamsters which were inoculated intraperitoneally with 10(5) plaque-forming units of the D variant of encephalomyocarditis virus (EMC-D) were examined virologically and histologically. Viral replication was detected from 1 day post inoculation (1 DPI), became more prominent 3 DPI, and was no longer demonstrated 7 DPI. The weight of testis decreased in course of time and it was about 2% of that of control 6 weeks post inoculation (6 WPI). Histopathologically, degeneration and/or necrosis of germinal cells and spermatogonia were observed in many seminiferous tubules of all hamsters 3 DPI. At 7 DPI, luminal obstruction by cellular debris and subsequent replacement of them by mesenchymal cells were common in mildly atrophic tubules surrounded with inflammatory cells. Thereafter, atrophy of seminiferous tubules became severer with the lapse of time and, in addition to plasma cell infiltration, apparent increase in the number of Leydig cells was found in the interstices. No regenerative signs of germinal epithelia were detected by 6 WPI. This is the first report of EMC virus-induced orchitis.     

Light cells within the limiting membrane of rat seminiferous tubules

Light-staining cells, distinct from myoid cells, were identified in electron micrographs of the limiting membrane of rat seminiferous tubules. While these cells were also found free in the interstitial space, they were observed mostly in the myoid cell layer of the limiting membrane but were never seen within the seminiferous epithelium itself. The light cells were characterized by a pale-stained cytoplasm containing a spheroidal Golgi apparatus next to a polymorphous often kidney-shaped nucleus, a few cisternae of rough endoplasmic reticulum and some granules of various types including multivesicular bodies. In hematoxylin-stained whole mounts of dissected tubules, these light cells were readily identified under the light microscope by nuclear morphology and light-staining juxtanuclear Golgi apparatus. The incidence of these cells, per unit surface area of tubular wall, was calculated, taking into consideration the stages of the cycle of the seminiferous epithelium with which they were associated. Distributed along the entire length of seminiferous tubules, their number varied significantly during the cycle. Low numbers were found in stages II–IV and XIII of the cycle, while high numbers were found in stages IX to XII and XIV–I of the cycle. These observations indicate that the seminiferous epithelium may exert an influence on the population of light cells present in the tubular limiting membrane.     

孕期非那雄胺暴露致子代雄性小鼠生殖器官发育异常

目的:探讨孕期非那雄胺暴露对子代雄性小鼠生殖器官发育的影响。方法:CD-1小鼠在受孕后0~17 d给予非那雄胺处理,通过宏观观察、解剖分析与组织形态学染色观察子代雄性小鼠生殖器官的发育情况;通过免疫荧光染色分析子代雄性小鼠精子发生情况。结果:宏观观察结果显示,孕期非那雄胺暴露可导致子代雄性小鼠外生殖器官畸形,表现为阴囊未完全融合及阴茎畸形;此外,还观察到小鼠肛门与生殖器的距离显著缩短(P<0.01)。解剖分析结果显示,孕期非那雄胺暴露可导致子代雄性小鼠睾丸不同程度的不完全下降及长度显著缩短(P<0.01)。组织形态学结果显示,各阶段阴茎长度均显著缩短(P<0.01);睾丸生精小管密度和生精小管管腔成熟精子数均显著降低(P<0.01),生精小管管腔和睾丸间质间隙均显著增大(P<0.01)。免疫荧光染色结果显示,睾丸中支持细胞、睾丸间质细胞和精原细胞的密度均显著降低(P<0.01);生精小管细胞的caspase-3荧光强度显著增加(P<0.01),Ki67与沙漠刺猬因子(desert hedgehog,Dhh)荧光强度均显著降低(P<0.01)。结论:孕期非那雄胺暴露可导致子代小鼠生殖器官发育异常并影响精子发生。     

The Human Blood-Testis Barrier in Impaired Spermatogenesis

The aim of this study was to explore the competence of the blood-testis barrier (BTB) using electron opaque tracers in diverse human testicular pathologies associated with Sertoli cell only syndrome. Two groups of patients were studied: (1) those with complete depletion (absence) of germ cells, and (2) those with severe germ cell depletion but with some germ cells left in the seminiferous epithelium. The first situation was associated with cryptorchidism with absence of germinal cells, idiopathic cases of aplasia of germ cells, peritumoral areas surrounding small seminomas where the seminiferous tubules were observed to contain a predominant population of Sertoli cells, or long estrogen treatment. The second was found also in cryptorchidism with early germ cells, idiopathic azoospermia, and oligospermia associated with sterility. In the first situation, seminiferous tubules lacked lumen and Sertoli cells had immature morphological characteristics, i.e., oval nuclei with smooth profiles, even heterochromatin distribution and a single, small nucleolus. Inter-Sertoli tight junctions were tortuous, interrupted, and mostly perpendicular to the basal lamina. Lanthanum hydroxide or nickel nitrate permeated most of the inter-Sertoli spaces, indicating disruption of the BTB. In the second situation, seminiferous tubules had a lumen, and Sertoli cells exhibited a mature appearance with large tripartite nucleoli and irregular, highly infolded nucleo-lemma. Only spermatogonia or primary spermatocytes showing diverse degrees of cell involution were found. Numerous inter-Sertoli tight junctions, uninterrupted and parallel to the basal lamina, stopped the electron opaque intercellular tracers close to it; this meant the assembly of a competent BTB. Therefore, a close correlation was found between morphological parameters of Sertoli cell maturity, including their tight junction organization, and BTB integrity.     

Germ cell transfer into rat, bovine, monkey and human testes.

Germ cell transplantation is a potentially valuable technique offering oncological patients gonadal protection by reinitiating spermatogenesis from stem cells which were reinfused into the seminiferous tubules. In order to achieve an intratubular germ cell transfer, intratubular microinjection, efferent duct injections and rete testis injections were applied on dissected testes of four different species: rat, bull, monkey and man. Ultrasound-guided intratesticular rete testis injection was the best and least invasive injection technique with maximal infusion efficiency for larger testes. Deep infiltration of seminiferous tubules was only achieved in immature or partially regressed testes. This technique was applied in vivo on two cynomolgus monkeys. In the first monkey a deep infusion of injected cells and dye into the lumen of the seminiferous tubules was achieved. In the second, transplanted germ cells were present in the seminiferous epithelium 4 weeks after the transfer. These cells were morphologically identified as B-spermatogonia and located at the base of the seminiferous epithelium. In summary, this paper describes a promising approach for germ cell infusion into large testes. The application of this technique is the first successful attempt of a germ cell transfer in a primate.     

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.     

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     

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.     

Lactate inhibits germ cell apoptosis in the human testis

Dysregulation of male germ cell apoptosis has been associated with the pathogenesis of male infertility. Therefore, factors involved in the regulation of germ cell death are being actively investigated. Here, we studied the effects of lactate on human male germ cell death, using as a model a testis tissue culture in which physiological contacts are maintained between the germ cells and the supportive somatic Sertoli cells. Apoptosis of spermatocytes, spermatids and a few spermatogonia was induced by culturing segments of seminiferous tubules under serum-free conditions. This germ cell death was inhibited effectively and dose-dependently by lactate, indicating that it plays a crucial role in controlling cell death cascades of male germ cells. Interestingly, the anti-apoptotic role of lactate was not associated with changes in testicular adenine nucleotide (ATP, ADP and AMP) levels. In the seminiferous tubules, the final site of the death-suppressing action of lactate appeared to be downstream along the cell death pathway activated by the Fas receptor of the germ cells. In conclusion, testicular cell death was effectively regulated by lactate, which may be regarded as a potential compound for optimizing in-vitro methods involving male germ cells for assisted reproduction.     

Three-dimensional structure of seminiferous tubules in the Syrian hamster

The hamster is useful for the study of male reproductive biology. However, unlike in the mouse and rat, the gross structure of seminiferous tubules in the hamster is largely unknown. The aim of the present study was to clarify the precise 3-dimensional (3D) structure of seminiferous tubules in hamsters. We reconstructed all seminiferous tubules in 3 and 1 testes from 0-day (P0) and 10-week (adult) Syrian hamsters, respectively, using serial paraffin sections and high-performance 3D reconstruction software. In P0 hamsters, the average numbers of seminiferous tubules, terminating points, branching points, and blind ends per testis were 9.0, 89.7, 93.0, and 0.7, respectively. There were two types of tubules: shorter and dominant ones. The dominant tubules, 2–4 in number per testis and accounting for 86% of the total tubule length, had many terminating and branching points and appeared to be derived from the anastomosis of many shorter tubules. In an adult hamster, there were 11 seminiferous tubules with a total length of 22 m, 98 terminating points, 88 branching points, and 2 blind ends per testis. Three of the 11 tubules were dominant ones, accounting for 83% of the total length, and occupied the testis from the surface over the circumference to the center, while the others were short and occupied only one side of the testis. The amplitude and direction of the curves of tubules were random, and there were no funnel-shaped networks of tubules present, in contrast to the mouse testis. The present study revealed the 3D structure of seminiferous tubules in developing and adult Syrian hamsters, which is different from that in mice and rats.     

大鼠生精小管体视学及PCNA、凋亡表达的发育变化研究

目的　探讨大鼠生精小管面积、管腔等体视学参数与生精细胞增殖、凋亡在发育过程中的变化及其之间的关系。　方法　应用免疫细胞化学、凋亡细胞原位检测和图像分析技术。　结果　大鼠从出生后生精小管平均面积逐渐增加 ,于生后 3月龄时达到最大 ,除与生后 6月龄组差异不显著外 ,与其他各组间差异显著 (P <0 0 5 ) ,6月龄后生精小管面积逐渐减少 ,2 5月龄时生精小管面积与 3周龄时相当 ;生精小管在 3周龄时开始出现管腔 ,在生后 6月龄时其平均面积最大 ,与其他各组间差异显著或极显著 (P <0 0 5或P <0 0 1) ,至生后 2 5月龄 ,管腔不明显 ,多被结缔组织填充 ;生精细胞间于生后 10月龄开始出现空泡 ,生后 2 5月龄空泡化明显 ,生精小管基膜及间质血管增生严重。PCNA及凋亡的阳性表达在生后 3周龄出现高峰 ,生后 2 5月龄细胞凋亡又出现 1个高峰。　结论　 1 生后 3周龄至 3月龄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。 2 生后一定阶段生精小管管腔的出现与生精细胞的凋亡有关 ,而生精小管管腔的出现有利于精子的生成与运输。 3 衰老大鼠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     

猕猴输精管内注射高分子聚合物HFMC后对睾丸组织结构的影响

本实验选用具有生育力成年雄性猕猴７只，在直视下行双侧ＨＦＭＣ输精管内注射，每侧剂量分别为３０ｍｇ１只，６０ｍｇ和１００ｍｇ各３只；于注射后２．５年和３．５年分别处死动物，取睾丸组织进行光镜和电镜观察．结果发现：猕猴注射ＨＦＭＣ２．５年后，睾丸光镜大部分曲细精管生精上皮结构完整，排列整齐。仅见局部少数管腔生精上皮层数减少，上皮细胞轻度水样变性等病理改变。电镜下曲细精管内除支持细胞内脂褐素增多，轻度基底膜增厚和精母细胞内质网扩张外，各级生精细胞，支持细胞及细胞间连接复合体等超微结构未见明显异常。注射ＨＦＭＣ３．５年后猕猴的光镜、电镜结果与注射后２．５年结果相似，但局部改变较２．５年组轻。上述结果表明：猕猴输精管内注射一定剂量ＨＦＭＣ节育不会引起睾丸组织的严重病理改变。但是，由于注射ＨＦＭＣ后，ＨＦＭＣ释放Ｈ＋及其对输精管的暂时阻塞，改变了精子生存的内环境，使睾丸出现局部轻度病理改变，随着ＨＦＭＣ逐渐溶解排出，睾丸功能相继恢复正常，配对产仔。为ＨＦＭＣ应用提供了安全性依据。     

Hypospermatogenesis is the Cause of Infertility in the Male Weaver Mutant Mouse

The pathologic phenotype of the testis in both prepuberal and postpuberal male weaver mutant mice was studied by light microscopy. Morphometric analysis of seminiferous tubules was carried out. Epididymal fluid was examined for the presence of spermatozoa. The seminiferous tubules of 21-day-old prepuberal weaver mutant mice lacked patent lumina and had more degenerated cells than control mice. Fifty-six day-old weaver mutants had many germinal epithelial cells located within the adluminal compartment that were in advanced stages of degeneration. Round spermatids were enlarged and multinucleated. Round spermatids and spermatocytes had sloughed into the lumen. Compared to control mice, elongated spermatids were seen less frequently. In older weaver mice, the degenerative process involved germ cells in both the adluminal and basal compartments. In 143- and 226- day-old weaver mutants, the Sertoli cells were atrophic. Diameters of seminiferous tubules in weaver mice were significantly reduced when compared to control mice. Sperm were either absent or very low in number in the epididymal fluid of postpuberal weaver mice. We conclude that spermatogenesis is abnormal in male weaver mutant mice. The testicular phenotype is characterized by a degenerative process that affects both germ cells and supporting cells.