Endocrine profile and testicular histomorphometry at puberty in rat offspring from diabetic mothers

This investigation was conducted to evaluate the effects of maternal diabetes on foetal testicular structure and function and reproductive hormone levels. Sixteen adult female rats were divided in two groups. Diabetes was induced in one group by alloxan. Both groups became pregnant by natural mating. Blood was collected from 60-day-old male offspring from both groups and the level of testosterone, FSH and LH measured in their serum. At the same time, the weight and volume of testes and various histological parameters from testicular histological sections were determined. Results showed significant decrease in LH, FSH and testosterone in sera of offspring from diabetic mothers (ODM) compared with the control group. Body weight and weight and volume of testes from ODM were about 25.5%, 51.6% and 50.8% higher respectively than those of the control group (P < 0.05). Number of seminiferous tubules increased (+15%) significantly (P < 0.05), whilst thickness of testicular capsule (−16%), number of Leydig cells (−14%), number of Sertoli cells (−10%), number of spermatogonia (−38%) and diameter of seminiferous tubules (−17%) showed significantly reduced values in the ODM compared to controls (P < 0.05). In conclusion, maternal hyperglycaemia has deleterious effects on testicular parameters during foetal life which will affect reproductive endocrinology during puberty and may impact on fertility.     

Histological and morphometric analyses of seasonal testicular variations in the Jungle Crow (<Emphasis Type="Italic">Corvus macrorhynchos</Emphasis>)

A histological and morphometric study was conducted to examine the seasonal testicular variations in the Jungle Crow (Corvus macrorhynchos) of the Kanto area, Japan, from January to July. The paired testes mass, diameter and number of germ cells of the seminiferous tubules, and proportion of seminiferous tubule area and interstitium were examined. Hematoxylin and eosin-stained testis sections and ImageJ Software were used. Paired testes weight was found to increase by 55-fold from January to late March–early May, thereafter declining by 18-fold by June–July. Seminiferous tubule diameter increased fivefold from January to late March–early May, followed a fourfold decrease in June–July. The increase in testes weight correlated well with the increase in the diameter of the seminiferous tubule. In January, the seminiferous tubules constituted 56% of the testicular tissue and the interstitium 44%. During late March–early May, there was very little testicular interstitium (7.9%), and the seminiferous tubules were significantly enlarged (P < 0.05) (92%); this was followed by a gradual increase in the interstitial regression of testes. In January, the seminiferous epithelium contained a single layer of spermatogonia and Sertoli cells. The number of spermatogonia, primary and secondary spermatocytes, spermatids, and maturing spermatozoa were significantly increased (P < 0.05) in late March–early May, followed by regression from mid May. Our results indicate that the Jungle Crow has a non-breeding season in January, a pre-breeding season during February–mid March, a main breeding season during late March–early May, a transition period during mid May–late May, and a post-breeding season beginning in June.     

An autopsy case of primary mixed choriocarcinoma and mature teratoma located in the thymic region associated with elevated human chorionic gonadotropin levels and characteristic testicular changes

An autopsy case of a 19-year-old male Japanese student with a primary mixed choriocarcinoma and mature teratoma in the thymic region is reported. The patient died 7 days after he first noticed fever and dyspnea. On autopsy, an anterior mediastinal mass was found to be in contact with the thymic gland. The mass weighed 270 g and measured 12.5 cm × 10 cm × 5 cm. The left thoracic cavity contained 2200 ml bloody pleural effusion and 200 g coagula due to hemorrhage from the tumor. Metastasized choriocarcinoma was seen in both lungs and the liver. High serum levels of human chorionic gonadotropin (HCG, 1 634 000 mIU/ml) and a decreased weight of the testes (2.0 g each) with Leydig cell hyperplasia/hypertrophy and the seminiferous tubules with hyaline ghost tubules or Sertoli cell only tubules were seen; other male reproductive organs were histologically normal. Although the serum testosterone level was within the normal range (5.75 ng/ml), luteinizing hormone (LH, 0.1 mIU/ml) and follicle-stimulating hormone (FSH, 0.3 mIU/ml) levels were decreased. High serum levels of HCG and characteristic testicular changes are drscribed.     

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

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

Hormonal response to Taekwondo fighting simulation in elite adolescent athletes

Exercise training efficiency depends on the training load, as well as on the athlete’s ability to tolerate it. The aim of the present study was to evaluate the effect of fighting simulation (3 fights, 6 min each, 30 min rest between fights) on anabolic (IGF-I, LH, FSH, estradiol, and testosterone) and catabolic hormones (cortisol) in elite, male (n = 10) and female (n = 10) adolescent (12–17 years) Taekwondo fighters. Blood samples were collected before the first and immediately after the third fight. The fighting simulation practice led to significant (p < 0.05) decreases in IGF-I (males −27.1 ± 25.6, females −22.4 ± 36.3 ng/ml), LH (males −0.7 ± 1.2, females −2.3 ± 3.3 U/L), and FSH (males −0.9 ± 0.5, females −1.5 ± 1.1 U/L), and to a significant increase (p < 0.05) in cortisol (males 141.9 ± 30.1, females 64.1 ± 30.6 mcg/dL) in both genders. Fighting simulation decreases in testosterone (males −1.9 ± 1.6, females −0.02 ± 0.06 ng/mL), and free androgen index (males −20.1 ± 21.5, females −0.3 ± 0.5) were significant (p < 0.05) only in male fighters. Exercise had no significant effect on estradiol, sex-hormone-binding globulins or thyroid function tests. Our data demonstrate that the physiologic and psychologic strain of a Taekwondo fighting simulation day led to a catabolic-type circulating hormonal response.     

Reinitiation of spermatogenesis by exogenous gonadotropins in a seasonal breeder,the woodchuck (Marmota monax), during gonadal inactivity

The present study was undertaken (1) to document structural and functional changes in the testes of seasonally breeding woodchuck during active and inactive states of spermatogenesis and (2) to evaluate the ability of exogenous gonadotropins to reinitiate spermatogenesis outside the breeding season. During seasonal gonadal inactivity, there were significant (P < 0.05) reductions in volumes of several testicular features (testis, seminiferous tubules, tubular lumen, interstitial tissue, individual Leydig cells, Leydig cell nuclei, and Leydig cell cytoplasm) as compared with gonadally active animals. The diameter of the seminiferous tubules was decreased by 26%, and Leydig cell numbers also declined in the regressed testes. These changes were accompanied by a decline in testosterone (T) levels in both plasma and testis, and reduction in epithelial height of accessory reproductive organs. A hormonal regimen was developed that would reinitiate spermatogenesis in captive, sexually quiescent woodchucks. A combination of PMSG and hCG markedly stimulated testicular growth and function and restored spermatogenesis qualitatively. Quantitatively normal spermatogenesis was restored in 2 of 6 treated males. Morphometric analyses revealed substantial increases in seminiferous tubular diameter and in the volume of seminiferous tubules, tubular lumen, total Levdig cells, and individual Leydig cells in the hormone-treated animals. These increased values corresponded to 99, 75, 68, 51, and 200%, respectively, of the values measured in naturally active woodchucks. Leydig cell numbers, however, remained unchanged and approximated only 31% of the number found in naturally active testes. Hormonal stimulation also resulted in a significant rise in serum T as well as in the total content of testicular T, and a marked increase in epithelial height in various accessory reproductive glands. The most effective hormonal protocol for stimulating spermatogenesis was treatment with 12.5 IU of PMSG twice a week for 4 weeks followed by 12.5 IU of PMSG + 25 IU of hCG twice a week for 4 weeks.     

Cell-cell interactions in the control of spermatogenesis as studied using leydig cell destruction and testosterone replacement

This review centers around studies which have used ethane dimethane sulphonate (EDS) selectively to destroy all of the Leydig cells in the adult rat testis. With additional manipulations such as testosterone replacement and/or experimental induction of severe seminiferous tubule damage in EDS-injected rats, the following questions have been addressed: (1) What are the roles and relative importance of testosterone and other non-androgenic Leydig cell products in normal spermatogenesis and testicular function in general? (2) What are the factors controlling Leydig cell proliferation and maturation? (3) Is it the Leydig cells or the seminiferous tubules (or both) which control the testicular vasculature? The findings emphasize that in the normal adult rat testis there is a complex interaction between the Leydig cells, the Sertoli (and/or peritubular) cells, the germ cells, and the vasculature, and that testosterone, but not other Leydig cell products, plays a central role in many of these interactions. The Leydig cells drive spermatogenesis via the secretion of testosterone which acts on the Sertoli and/or peritubular cells to create an environment which enables normal progression of germ cells through stage VII of the spermatogenic cycle. In addition, testosterone is involved in the control of the vasculature, and hence the formation of testicular interstitial fluid, presumably again via effects on the Sertoli and/or peritubular cells. When Leydig cells regenerate and mature after their destruction by EDS, it can be shown that both the rate and the location of regenerating Leydig cells is determined by an interplay between endocrine (LH and perhaps FSH) and paracrine factors; the latter emanate from the seminiferous tubules and are determined by the germ cell complement. Taken together with other data on the paracrine control of Leydig cell testosterone secretion by the seminiferous tubules, these findings demonstrate that the functions of all of the cell types in the testis are interwoven in a highly organized manner. This has considerable implications with regard to the concentration of research effort on in vitro studies of the testis, and is discussed together with the need for a multidisciplinary approach if the complex control of spermatogenesis is ever to be properly understood.     

Leydig cell micronodules are a common finding in testicular biopsies from men with impaired spermatogenesis and are associated with decreased testosterone/LH ratio

To assess the biological significance of Leydig cell 'hyperplasia' in man, Leydig cell distribution, volume, and function were studied in patients with infertility or testicular cancer and in suddenly deceased controls. A total of 156 biopsies from 95 patients and 18 necropsies from 13 controls were examined using a semi-quantitative stereological method. In patients, serum concentrations of testosterone, sex hormone binding globulin (SHBG), luteinizing hormone (LH), follicle stimulating hormone (FSH), oestradiol and inhibin-B were correlated with the findings on histological examination. Leydig cell clusters of more than 15 cells in a cross-section, for which we proposed the name 'micronodules', were frequently seen in testicles exhibiting Sertoli-cell-only syndrome (SCO), a mixed pattern of impaired spermatogenesis, or complete spermatogenesis in combination with elevated FSH. Median numbers of micronodules per 1.77 mm(2) (four fields of vision) in these three histological patterns were 6, 4, and 3.5, respectively. In contrast, micronodules were only occasionally observed in testicular biopsies from patients with complete spermatogenesis and normal gonadotrophin levels (median 1), and were rare in testes from controls (median = 0, p = 0.02). The proportion of testicular tissue occupied by Leydig cells increased with decreasing spermatogenic capacity. In contrast, the total volume of Leydig cells per testis was roughly comparable irrespective of the histological pattern, with the exception of testes with bilateral micronodules, which had significantly increased Leydig cell volume compared to those without micronodules. The number of micronodules correlated positively to LH (r = 0.577, p < 0.01) and FSH (r = 0.595, p < 0.01) and the presence of micronodules was most pronounced in the hyperstimulated testes, as reflected by an increased LH/testosterone ratio. In conclusion, Leydig cell micronodules were more frequent in biopsies with impaired spermatogenesis and associated with decreased ratios of testicular hormones to gonadotrophins. The presence of micronodules thus seems to be a histological marker of testicular failure in man.     

Efficacy of naringenin against permethrin‐induced testicular toxicity in rats

Permethrin (PM), a synthetic pyrethroid insecticide, has broad toxicity spectra. We aimed to investigate the effects of PM on the testes of adult albino rats, examine the recovery response and evaluate the efficacy of naringenin (NG) supplementation. Adult male albino rats were randomly assigned to five groups of six each: control, NG (50 mg/kg), PM (70 mg/kg), recovery (after subsequent withdrawal of PM) and NG‐PM group. All treatments were given by oral gavage for 6 weeks and another 3 weeks for the recovery group. At the time of sacrifice, each testis was weighed. Biochemical analysis of epididymal sperm count and serum testosterone level was performed. Testes were processed for histological, ultrastructural and c‐Kit immunohistochemical study. PM toxicity was evidenced by a highly significant decrease in testicular weight, epididymal sperm count and serum testosterone level compared to control. Furthermore, testicular structure abnormalities and reduced c‐Kit immunoreactions were observed. Stoppage of PM in the recovery group partially reversed PM‐induced changes. There was a mild decrease in testicular weight and biochemical parameters compared to control. The structure of seminiferous tubules was partially retained. The NG‐PM group showed an overall improvement in testicular weight and biochemical alterations which were confirmed by light and electron microscopic examination. In conclusion, PM induced testicular toxicity, which was ameliorated by NG co‐administration. However, stoppage of PM exposure was associated with partial recovery.     

Herpes simplex virus inoculation in murine rete testis results in irreversible testicular damage

This study aimed to establish the influence of herpes simplex virus (HSV) on testis morphology and germ cell development using a model of ascending urogenital HSV infection in mice. Adult C57BL/6J mice were inoculated with 100 plaque‐forming units of HSV1 in rete testis. Viral proteins and HSV DNA were detected from 3 days postinoculation (DPI), while capsids and virions could be visualized at 6 DPI. Infectious activity of HSV was revealed by rapid culture method in testes from 3 to 14 DPI, and virus DNA by PCR – from 3 to 100 DPI. Germ and Sertoli cells were infected during the early stages of the infection, whereas interstitial cells only occasionally contained the virus at 21 and 45 DPI. Microscopic analysis revealed severe degeneration of the germinal epithelium in the infected testes. By 21 DPI, testes became atrophic and most Sertoli cells were destroyed. No testicular regeneration and no spermatozoa in the epididymis were observed at 45 and 100 DPI. From 3 DPI, inflammatory cells accumulated in the interstitium between damaged tubules; a significant increase in the number of CD4⁺, CD8⁺ T lymphocytes and F4/80⁺ cells was observed in the infected testes. This study shows that in the case of HSV retrograde ascent into seminiferous tubules, the acute viral infection results in irreversible atrophy of the germinal epithelium, orchitis and infertility. These results may be used to further study viral orchitis and the influence of HSV on spermatogenesis and male fertility.     

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.     

FSH in testes of marmosets during development: Immunocytochemical localization and de novo biosynthesis

Immunocytochemical localization of FSH was carried out in various cell types of marmoset testes during development using antisera generated against intact as well as β-subunit of human FSH. Significant differences in the intensity as well as distribution of FSH in various cell types were observed in neonatal, pubertal, and adult marmosets. Intensity of staining in Leydig cells was maximum at day 1 and in adults (1–3 years), whereas it was minimum at 3 months. In seminiferous tubules (Sertoli cells), FSH was present in trace amount until puberty and subsequently increased at maturity. Further studies demonstrate de novo biosynthesis of FSH-like moiety in vitro by testicular tissue, which was age dependent.     

FSH in testes of marmosets during development: immunocytochemical localization and de novo biosynthesis.

Immunocytochemical localization of FSH was carried out in various cell types of marmoset testes during development using antisera generated against intact as well as beta-subunit of human FSH. Significant differences in the intensity as well as distribution of FSH in various cell types were observed in neonatal, pubertal, and adult marmosets. Intensity of staining in Leydig cells was maximum at day 1 and in adults (1-3 years), whereas it was minimum at 3 months. In seminiferous tubules (Sertoli cells), FSH was present in trace amount until puberty and subsequently increased at maturity. Further studies demonstrate de novo biosynthesis of FSH-like moiety in vitro by testicular tissue, which was age dependent.     

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.     

Effects of long-term treatment with the anti-androgen bicalutamide on human testis: an ultrastructural and morphometric study

AIMS: To assess the effects of more than 4 years' treatment with the anti-androgen bicalutamide on human testis by clinical, ultrastructural and morphometric analysis. METHODS AND RESULTS: Two patients (aged 74 and 69 years) with prostate cancer were treated for more than 4 years with bicalutamide 50 mg daily. Clinical characterization and follow-up included luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone and prostate-specific antigen (PSA) measurements and clinical response of the tumours. Due to progression of the disease, patients underwent surgical orchidectomy as a further androgen withdrawal therapy. Testis biopsies were studied by light and electron microscopy and analysed by morphometry. Control samples were obtained from the normal testis of two patients with testicular cancer who underwent orchidectomy. Clinical follow-up showed a good response in the control of tumour growth and serum PSA decreased to < 4 ng/mL; concentrations of serum LH, FSH and testosterone were within the normal range. Testicular morphology of treated patients was unexpectedly well preserved; the organization of seminiferous tubules was normal with all the germ line elements and mature spermatozoa present. In some areas, a net increase of peritubular connective tissue was evident which may be a consequence of the age of the patients. CONCLUSIONS: Long-term bicalutamide (50 mg) treatment appears to have very little impact on testis ultrastructure and sperm maturation, while it is effective in the control of androgen-dependent prostatic tumours.     

克氏综合征睾丸体积大小与性激素的相关性及睾丸组织超微结构的研究

目的探讨克氏综合征睾丸体积大小与性激素的相关性及造成克氏综合征男性不育的发病机理。方法对20例克氏综合征患者和10例正常对照组血清进行性激素测定，同时作睾丸组织活检进行病理切片及电镜超薄切片观察。结果克氏综合征与正常对照组睾丸体积、生精小管直径和管壁厚度及血清FSH、LH、T之间均有极显著的差异（P〈0．001），患者睾丸体积大小与FSH和LH值呈负相关性，与T值呈正相关性；睾丸组织超微结构观察结果表明生精小管界膜有不同程度的显著异常变化，主要表现为界膜增厚及纤维化增生，基膜增厚及纤维化增生，肌样细胞的空泡状变性或去分化增生。支持细胞病理变化呈现多样性特征，胞质内有大量内质网呈空泡状变性，部分线粒体扩张。间质内血管壁明显增厚及血管内皮细胞肿胀，基膜及血管腔内大量胶原纤维增生。结论推导出患者睾丸体积大小与FSH、LH、T的多重相关回归方程；同时认为克氏综合征睾丸组织结构发生严重的纤维化增生，促使其生精细胞形成过程发生早期的、程度严重的障碍和病理学变化，这是造成其男性不育的主要原因。     

Seasonal changes in the hypothalamo‐pituitary‐testes axis of the japanese wood mouse (Apodemus speciosus)

Seasonal changes in the hypothalamo‐pituitary‐testes axis of the Japanese wood mice (Apodemus speciosus) were studied. The testes, epididymis, pituitary and hypothalamus were compared between mice in the breeding season (July) and non‐breeding season (October) using morphological techniques, and the plasma testosterone level was evaluated by enzyme immunoassay. Significant differences in these tissues were observed between the breeding season and the non‐breeding season. Specifically, differences in the non‐breeding season included 1) a decline in testicular and epididymal weights, arrest of spermatogenesis and decrease of serum testosterone concentration; 2) a decrease in the number of luteinizing hormone (LH)‐, follicle stimulating hormone (FSH)‐, prolactin (PRL)‐, and growth hormone (GH)‐immunoreactive cells, and decrease in the size of FSH, PRL, and GH‐immunoreactive cells; and 3) an increase in the size of gonadotropin‐releasing hormone (GnRH)‐immunoreactive neurons. Our findings indicate that the male adult Japanese wood mouse exhibits unique seasonal changes in the hypothalamo‐pituitary‐testes axis which are not found in laboratory mice. Anat Rec 260:366–372, 2000. © 2000 Wiley‐Liss, Inc.     

Natural history of seminiferous tubule degeneration in Klinefelter syndrome

Klinefelter syndrome (47,XXY) is characterized by small, firm testis, gynaecomastia, azoospermia and hypergonadotropic hypogonadism. Degeneration of the seminiferous tubules in 47,XXY males is a well-described phenomenon. It begins in the fetus, progresses through infancy and accelerates dramatically at the time of puberty with complete hyalinization of the seminiferous tubules, although a few tubules with spermatogenesis may be present in adult life. Activation of the pituitary-gonadal axis at 3 months of age is seen in Klinefelter boys similar to healthy boys. However, the level of testosterone in Klinefelter boys is significantly lower than in controls. After this 'minipuberty', the hormone levels decline to normal prepubertal levels until puberty. In puberty, an initial rise in testosterone, inhibin B, LH and FSH occurs in Klinefelter boys. However, the rise in testosterone levels off and ends at a low-normal level in young adults. Likewise, serum concentration of inhibin B exhibits a dramatic decline to a low, often undetectable level, concomitantly with a rise in FSH, reflecting the degeneration of the seminiferous tubules. Many hypotheses about the underlying mechanism of the depletion of the germ cells in Klinefelter males have been reported and include insufficient supranumerary X-chromosome inactivation, Leydig cell insufficiency and disturbed regulation of apoptosis of Sertoli and Leydig cells. However, at present, the exact mechanism remains unclear. In this article, we summarize current knowledge on the development of the classical endocrinological and histological features of 47,XXY males from fetus to adulthood and review the literature concerning the degeneration of the seminiferous tubules in this syndrome.     

Inhibin B plasma concentrations in oligozoospermic subjects before and after therapy with follicle stimulating hormone

The aim of this study was to investigate inhibin B and follicle stimulating hormone (FSH) secretion in a large group of oligozoospermic subjects affected by different degrees of testicular damage, before and after FSH treatment. A total of 135 oligozoospermic subjects (sperm count < 20 x 10(6)/ml) were evaluated for seminal parameters and FSH, luteinizing hormone (LH), testosterone and inhibin B plasma concentrations. Testicular structure was analysed with bilateral fine needle aspiration cytology. Inhibin B showed an inverse correlation with FSH, no correlation with sperm concentration and a significant relationship with intratesticular spermatid number, demonstrating that testicular spermatids play an important role in the control of inhibin B production. Twenty-five subjects with sperm counts < 10 x 10(6)/ml were treated with FSH; 11 of these had basal FSH and inhibin B plasma concentrations in the normal range (group A), while in seven subjects FSH was elevated (> 7 IU/l) with normal inhibin B (group B), and in seven patients FSH was high and inhibin B reduced (< 80 pg/ml) (group C). During treatment, in group A patients inhibin B plasma concentrations increased significantly after 2, 3 and 4 weeks of FSH administration and declined thereafter to pre-treatment concentrations. Groups B and C did not show any modification during the treatment. In the same period, in group A FSH increased significantly after 2, 3 and 4 weeks and subsequently declined. In groups B and C, FSH increased significantly after 2 weeks and remained elevated during the following period. The results of the present study confirm the significant inverse correlation between inhibin B and FSH plasma concentrations in subjects with disturbed spermatogenesis, and demonstrate that inhibin B reflects Sertoli cell function and their interaction with spermatids. FSH and inhibin B concentrations are an expression of the spermatogenic status of seminiferous tubules. FSH treatment seems to modify inhibin B plasma concentrations only in subjects with normal basal FSH and inhibin B, independently from the effects of this therapy on sperm production.     

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)