Testosterone and spermatogenesis. Identification of stage-specific, androgen-regulated proteins secreted by adult rat seminiferous tubules.

The aim of this study was to identify potential androgen-regulated proteins (ARP) that might mediate the supportive effects of testosterone on spermatogenesis. Adult rats were injected with ethane dimethane sulphonate (EDS) to destroy Leydig cells and thus induce complete testosterone withdrawal. Other EDS-treated rats were injected with 25 mg testosterone esters (TE) every 3 days to maintain quantitatively normal spermatogenesis. A timeframe for the study of androgen action on spermatogenesis was deduced from enumeration of degenerating germ cells at stage VII of the spermatogenic cycle in perfusion-fixed testes from rats in the early stages (4 to 8 days) after EDS treatment. Based on this data and changes in testicular interstitial fluid volume, long seminiferous tubule segments were isolated from control rats and from EDS-treated rats (+/- TE-supplementation) at stages II-V, VI-VIII, or IX-XII, 2 days to 6 days after EDS treatment. Seminiferous tubule segments were incubated for 22 hours with 60 microCi 35S-labelled methionine. Incorporation into newly synthesized proteins in the seminiferous tubule culture medium (= secreted proteins) or in seminiferous tubule lysates (= intracellular proteins) was determined by trichloroacetic acid-precipitation followed by analysis using two-dimensional sodium dodecylsulfate polyacrylamide gel electrophoresis. In control rats, incorporation of 35S-methionine into proteins secreted by isolated seminiferous tubules was more than twice as great at stages VI-VIII than at stages II-V or IX-XII. This doubling in methionine incorporation into stages VI-VIII secreted proteins was abolished, however, 4 days after EDS treatment (when germ cell degeneration at stage VII was only just evident). A similar change occurred 4 days after testosterone withdrawal induced by immunoneutralization of luteinizing hormone. In the latter case and after EDS treatment, TE-supplementation of rats from day 0 maintained the normal control pattern of methionine incorporation into seminiferous tubule secreted proteins, although 6 days after EDS and TE treatment, incorporation into stages VI-VIII secreted proteins was 19% lower (P less than 0.05) than in the control group. In contrast, incorporation of methionine into proteins secreted by seminiferous tubules at stages II-V and IX-XII was unaffected by EDS and TE pretreatment, as was incorporation into intracellular proteins at all stages.(ABSTRACT TRUNCATED AT 400 WORDS)     

Assessment of the role of Leydig cell products other than testosterone in spermatogenesis and fertility in adult rats

Adult male rats were treated with ethane dimethanesulphonate (EDS) to destroy the Leydig cells and were then supplemented for 3-10 weeks with testosterone esters (TE) by injection every 3 days. The latter treatment prevented Leydig cell regeneration but maintained quantitatively the androgen-dependent aspects of spermatogenesis, as judged by germ cell counts at stage VII of the spermatogenic cycle. Other than the absence of Leydig cells, the testes of EDS-treated, TE-supplemented rats showed only two morphological changes, (1) the appearance of mast cells throughout the interstitium, and (2) a 3- to 4-fold increase in the number of degenerating germ cells (secondary spermatocytes) at stages XIV-I; this was reflected in a significant decrease in the ratio of spermatids to pachytene spermatocytes at stage VII. These changes were not observed in either oil-treated or TE-treated control rats although similar, but less marked, changes in cell degeneration at stages XIV-I were observed in rats actively immunized against oxytocin. Epididymal sperm number was reduced marginally (approximately 15%) in EDS-treated, TE-supplemented rats while sperm motility was affected even less. In a serial mating trial, some of these treated rats showed evidence of subfertility/infertility, but this was mostly transient and may have been the result of epididymal effects of EDS. These results suggest that Leydig cell products other than testosterone are not essential for maintenance of spermatogenesis and fertility in rats, although because of increased germ cell degeneration during the final stages of meiosis (perhaps as the result of oxytocin withdrawal), a small reduction in sperm count may occur.     

Local regulation of Leydig cells by the seminiferous tubules. Effect of short-term cryptorchidism

Unilateral cryptorchism was induced in adult rats for 24 h, and its effect on testicular morphology and intratesticular testosterone concentration after hCG-stimulation were studied. In seminiferous, tubules from abdominal testes an increased number of degenerating germ cells was noted in stages XIV-III of the spermatogenic cycle and Sertoli cells contained an increased amount of lipid droplets in stages XIV-VIII. However, germ cells and Sertoli cells from tubules at other stages of the cycle appeared unaffected. In scrotal testes the size of peritubular Leydig cells varied in phase with the spermatogenic cycle. The largest cells were found adjacent to stage VII-VIII and the smallest adjacent to stage XI-XII. In abdominal testes no stage-dependent variation in the size of peritubular Leydig cells was seen. Perivascular Leydig cells were of equal size in abdominal and scrotal testes. The testicular testosterone concentration following stimulation with a low dose of hCG was significantly lower in abdominal testes. It is suggested that the seminiferous tubules locally modulate Leydig cell function and that the stage specific stimulatory influence from stage VII-VIII is rapidly lost during experimental cryptorchidism.     

Êxpression of inducible nitric oxide synthase (iNOS) in the azoospermic human testis

Azoospermia, which is the absence of spermatozoa in the ejaculate, is not a rare cause of male infertility. Inducible nitric oxide synthase (iNOS) is a calcium-independent NOS, which is present in the testis and involved in spermatogenesis, and apoptosis of Sertoli and germ cells. Twenty idiopathic infertile men presenting nonobstructive azoospermia were enrolled in this study, and testicular sperm extraction procedures were performed. Tissue extracts were dissected, and the fluid samples were investigated to determine the presence of spermatozoa. Histologic evaluation of the spermatozoa-present samples revealed that seminiferous tubules were normal and were lined by Sertoli cells and spermatogenic cells. However, in the spermatozoa-absent samples, the diameter of the seminiferous tubules was small, and Sertoli-cell-only syndrome was determined in most of the tubules. iNOS expression was very weak in Sertoli cells, germ cells, and in Leydig cells in the spermatozoa-present group. In the spermatozoa-absent group, the immunostaining was very intense in Sertoli and Leydig cells. Electron microscopy findings were supported the histologic results. In conclusion, complete germ cell loss and intense expression of iNOS in the Sertoli and Leydig cells in the spermatozoa-absent groups of azoospermic human testis suggest an essential role of iNOS in spermatogenesis.     

The selective removal of pachytene spermatocytes using methoxy acetic acid as an approach to the study in vivo of paracrine interactions in the testis

Testicular weight and morphology, serum gonadotropins, intratesticular levels of testosterone and ABP levels in testicular interstitial fluid were studied in adult rats at intervals of 1 to 70 days after a single oral dose of 650 mg/kg methoxy acetic acid. At 3 days, this treatment resulted in the selective loss or depletion of pachytene and later spermatocytes from seminiferous tubules at all stages other than VIII to XI of the spermatogenic cycle. At later times this lesion was expressed as an absence mainly of round (14 days) or elongated (21 days) spermatids from the majority of seminiferous tubules. Other than these changes, spermatogenesis did not appear to be affected by treatment and was qualitatively normal in all tubules at 70 days after treatment. As deduced from cell counts at 3 days posttreatment, the initial action of methoxy acetic acid was restricted to late zygotene spermatocytes (stage XII) and pachytene spermatocytes at all stages other than early- to mid-stage VII. Levels of FSH in serum and those of ABP in testicular interstitial fluid indicated that Sertoli cell function was altered in rats treated with methoxy acetic acid. Both were increased at 1 to 3 days posttreatment, returned to normal at 7 to 14 days but were increased again at 21 days before finally returning to control levels at 28 days. In contrast, the levels of testosterone in serum, isolated seminiferous tubules and testicular interstitial fluid were unaffected by treatment, as also were the serum levels of LH. The two periods of increase in FSH and ABP levels coincided with the times of greatest decrease (approximately 20%) in testicular weight, and may be related either to the type of germ cell missing from the affected tubules and/or to the stage of the cycle of the affected (or unaffected) tubules. These data suggest that chemicals such as methoxy acetic acid may prove useful in the study of paracrine interactions in vivo.     

Immunohistochemical study of glutathione S-transferase in normal and experimental cryptorchid testes rats]

Using the antibody for glutathione S-transferase (GST) purified from human kidney, normal testes and experimental cryptorchid testes from newborn to 20-week-old rats were immunohistochemically stained by the peroxidase antiperoxidase (PAP) method. The cryptorchidism was surgically created at 1 week of age. The localization of GST was particularly examined by light microscopy, and the amount of Leydig cells was measured by a stereological method. 1. Leydig cells in the normal and cryptorchid testes showed strong GST activity at all ages. The amount of these cells in normal testes increased from 4 to 8 weeks of age and then slightly decreased, whereas in cryptorchid testes it was significantly larger than in the normal testes at 20 weeks of age, indicating hyperplasia of Leydig cells. 2. In the normal and cryptorchid testes, degenerating primary spermatocytes with GST activity appeared in the seminiferous tubules at 2 to 4 weeks of age. In the cryptorchid testis, degenerating germ cells with GST activity were also found in the regressing seminiferous tubules after 4 weeks of age. It is possible that GST acts as a detoxification system in the degenerating germ cells. 3. The PAP staining of GST in the rat testes is considered to be useful method for evaluating metabolic function of the spermatogenic cells and the distribution and amount of Leydig cells. 4. Experimental cryptorchidism showed that germ cells become sensitive after 4 weeks of age.     

Is testosterone involved in the initiation of spermatogenesis in humans? A clinicopathological presentation and physiological considerations in four patients with Leydig cell tumours of the testis or secondary Leydig cell hyperplasia

The purpose of this study was to evaluate the role of testosterone on the puberal development of spermatogenesis and to present additional clinicopathological data which bring about new information to this controversial subject. Four pre-pubertal patients are presented, 2 of them bearing Leydig cell tumours of the testis in the form of nodular masses. In both cases seminiferous tubules in the immediate vecinity to the tumours showed complete development of spermatogenesis, while those located away from the tumours were infantile in nature. Gonadotrophic levels were within the normal pre-pubertal range in these 2 cases. In one of the patients, testosterone concentration in the testis showed higher values than normal, and a concentration gradient was detected between the tumoral nodule and non-tumoral parenchyma. The 3rd patient had a pineal choriocarcinoma producing high amounts of hCG and consequently a diffuse hyperplasia of Leydig cells with high levels of plasma testosterone. Seminiferous tubules showed development up to pachytene spermatocytes. The last case was a precocious puberty in a boy with a tumour of the 3rd ventricle area. He had elevated levels of testosterone in the testis and plasma. In the testicular biopsy, stimulation of Leydig cells was detected. The seminiferous tubules showed mature Sertoli cells and pachytene spermatocytes. FSH levels were abnormally low. These 4 cases present in common different situations in which abnormally high amounts of testos-happens in the immature rat, the interaction between testosterone and gonadotrophins is essential for the normal initiation of spermatogenesis in normal puberty. Considerations are discussed on the possible synergistic role of gonadotrophins or other factors in relation with stimulation of seminiferous tubules by testosterone.     

Morphological alterations and intratubular lipid inclusions as indicative of spermatogenic damage in cimetidine-treated rats

Doses of cimetidine (50 mg/kg b/w) were administered to adult male Wistar rats over 52 consecutive days. Besides plasma testosterone levels, morphological and morphometric aspects of the seminiferous tubules as well as histochemical analysis of the lipid content by oil red O were emphasized. Abnormal tubules exhibiting disorganization of their cellular association, loss of germ cells, and multinucleated giant spermatids were usually found. Significant reductions of testis weight and tubular diameter at specific stages (VII-IX), as well as lack of contact between Sertoli cells and spermatids in tubules at stage IX, suggest a possible interference of cimetidine on the histoarchitecture of the seminiferous epithelium. The dense concentration of lipid inclusions in tubules at postspermiation stages indicates phagocytosis and degradation of germ cells. Since no change in serum testosterone levels was verified in cimetidine-treated rats, the authors could not exclude the possibility that besides an antiandrogenic effect, other biochemical factors necessary for normal spermatogenesis could be involved in the testicular alterations.     

Adverse effects of chronic GnRH antagonist administration on seminiferous epithelium in adult rats.

Seminiferous epithelium in adult rats was studied by light and electron microscopy after 5 weeks of chronic administration of GnRH antagonist (Ac-D2 Nal 1, D4ClPhe 2, DTrp 3, DArg 6, DAla 10; GnRH code-103-289-10, National Institutes of Health, USA). In these rats, the epithelium showed significant accumulation of vacuoles in more than 80% of the tubules, along with germ cell degeneration and nuclear pyknosis. Disruption in the process of spermatogenesis was also very much evident. In most of the tubules studied (greater than 90%), germ cell development was arrested beyond the pachytene spermatocyte stages. The vacuoles in the seminiferous epithelium were different sizes and when magnified were seen to consist of a thickened outer margin of solid nonfibrous coat within the Sertoli cell cytoplasm. Associated changes in the interstitium showed increased intertubular space but no inflammatory type of response. In actual cell counts, the decrease in the average number of macrophages was 32% and in Leydig cells 23%, while the total number of all types of cells in the interstitium was 30% less than that of the controls. Following the treatment, weights of testis, epididymis, seminal vesicle, and ventral prostate were drastically reduced. Rats treated with testosterone supplementation (60 micrograms/rat day) to GnRH antagonist recovered testicular and epididymal weights to approximately 57% and seminal vesicle and ventral prostate weights by 82.9 and 84%, respectively. Normalcy returned to the tubular epithelium and the interstitial cell counts were restored to original levels.     

Spermatogenic cycle length and spermatogenic efficiency in the gerbil (Meriones unguiculatus)

The gerbil (Meriones unguiculatus) is a rodent native of the arid regions of Mongolia and China. Because the gerbil can be easily bred in laboratory conditions, this species has been largely used as an experimental model in biomedical research. However, there is still little information concerning the testis structure and function in the gerbil. In this regard, we performed a detailed morpho-functional analysis of the gerbil testis and estimated the spermatogenic cycle length utilizing 3H-thymidine as a marker for germ cell progression during their evolution through the spermatogenic process. The stage frequencies of the XII stages characterized according to the acrosome formation and development were (I-XII) 13.8, 10.1, 8.1, 7.8, 4.0, 11.2, 7.5, 7.1, 5.9, 7.6, 8.1, and 8.9. The mean duration of each seminiferous epithelium cycle was determined to be 10.6 +/- 1.0 days and the total duration of spermatogenesis, based on 4.5 cycles, was approximately 47.5 days. The volume density of tubular and interstitial compartments was approximately 92% and 8%, respectively. Based on the volume occupied by seminiferous tubules in the testis and the tubular diameter, about 9 and 18 m of seminiferous tubules were found per testis and per gram of testis, respectively. Twelve primary spermatocytes were formed from each type A1 spermatogonia. The meiotic index was 2.8, indicating that 30% of cell loss occurs during meiosis. The number of Leydig and Sertoli cells per gram of the testis was 28 million and each Sertoli cell was able to support approximately 13 spermatids. The daily sperm production per gram of testis (spermatogenic efficiency) was 33 million. Taken together, these data indicate that, mainly due to the high seminiferous tubule volume density and Sertoli cell support capacity for germ cells, the gerbil presents high spermatogenic efficiency compared with other mammalian species already investigated. The data obtained in the present study might provide the basis for future research involving the reproductive biology in this species.     

Repeated interruptions of the testicular blood flow do not have long-term effects on spermatogenesis in the ram

Summary. The effect of repeated interruptions of the testicular blood flow on spermatogenesis was studied in mature Texel rams. Reversible interruption of the blood flow was achieved by an inflatable occluder, placed around the testicular artery at the level of the spermatic cord. In eight testes the blood flow was successfully interrupted six times for 1 h within 3 weeks and in 14 testes nine times for 1 h within 3 weeks. Nine weeks after the last blood flow interruption spermatogenesis was evaluated in histological sections of the testes. Both after six and nine blood flow interruptions a qualitatively complete epithelium was found in at least 90% of the seminiferous tubules. Cell counts in stages VII and VIII of the spermatogenic cycle revealed a slight decrease of spermatocytes and spermatids in the tubules with a complete epithelium after nine occlusions, which was only statistically significant for Preleptotene Spermatocytes. After six occlusions the numbers of all cell types were at or even slightly above control levels. These results show that repeated periods of ischaemia for 1 h do not result in conspicious long-term damage to spermatogenesis.     

Morphological and Histochemical Observations on the Prenatal and Postnatal Testes of the Field Rat (Millardia meltada)

The foetal testis of the field rat (Millardia meltada) shows seminiferous tubules and interstitium consisting of mesenchymal cells and differentiated Leydig cells associated with blood vessels. The tubules during the prenatal period show gonocytes and Sertoli cells. After birth, their diameter decreases but again increases progressively after postnatal days 9 and 10. Spermatogonia appear among the gonocytes on postnatal day 1 and primary spermatocytes on day 8. Secondary spermatocytes and spermatids are not seen up-to-day 23. Several hypertrophied Leydig cells are seen in the foetal testis on day 17 but are greatly increased in number on days 18 and 19. A few hours after birth the Leydig cells show a rapid decrease in their number. These fluctuations in the Leydig cells of prenatal and neonatal testes have been correlated to the rise and fall in testosterone production during these periods. The Leydig cells show the histochemical characteristics of actively steroid-secreting cells, which consist of the presence of diffuse lipoproteins and a few lipid granules consisting of phospholipids; no cholesterol and/or its esters could be demonstrated. Such lipids are not present in the cytoplasm of undifferentiated mesenchymal cells. The seminiferous tubules do not show any appreciable development of lipid changes.     

Testicular Biopsy and Hormonal Study in a Male with Noonan''s Syndrome

The testicular biopsy study of a 17-year-old male with Noonan's syndrome revealed seminiferous tubules of reduced diameter with hypospermatogenesis. Many spermatocytes underwent degeneration and many spermatids developed abnormal. The Sertoli cells were similar to immature Sertoli cells. Fully differentiated Leydig cells were rare while precursor Leydig cells were numerous. Both gonadotropin and testosterone levels were low, and a lack of response to LH-RH as well as to clomiphene was found. The testicular biopsy performed at 20 years of age revealed a certain maturation of the seminiferous tubules which increased the germ cell number. The abnormalities in the spermatogenesis as well as the immature appearance of Sertoli cells continued. Leydig cells were more numerous and showed a certain development without reaching the normal pattern. Gonadotropin levels were normal while testosterone levels low. The response to LH-RH was increased and the absence of response to clomiphene persisted. These features suggest a delayed puberty.     

Variation in the effect of a nongonadotropic Leydig cell stimulating factor in testicular interstitial fluid after exposure of the testis to a single episode of heat treatment

The activity of a nongonadotropic factor present in rat testicular interstitial fluid and capable of stimulating Leydig cell testosterone production was measured at intervals for 8 weeks after exposure of the testis to a single episode of heat treatment (43 C for 15 minutes). The activity of this factor was determined using a Leydig cell bioassay and the testicular albumin space (a measure of the interstitial fluid volume) was determined after the injection of 125I-labeled bovine serum albumin. Additionally, the response of interstitial cells to hCG stimulation was measured at each time point after heat treatment. The response of interstitial cells to hCG and the activity of the interstitial fluid were both increased transiently 2 or 3 weeks after heat treatment coincident with the disruption of spermatogenesis. These data provide further evidence for the local interaction of the tubules and interstitium and imply a role for the testicular interstitial fluid factor in these local regulatory mechanisms.     

Development of stage-specific paracrine regulation of Leydig cells by the seminiferous tubules

The size of peritubular Leydig cells surrounding tubules in different stages of the spermatogenic cycle was determined in 43- and 47-day-old male rats. A stage-dependent variation in the size of peritubular Leydig cells was not present in 43-day-old rats, but by 47 days those Leydig cells closely adjacent to tubules at stages VII-VIII were larger than others. At 43 days of age spermatogenesis had developed up to step 18 spermatids in late stage VI tubules. At 47 days of age the first mature sperm had just been released from the seminiferous epithelium, and consequently the first wave of the spermatogenic cycle was completed. Tubules at stages VII-VIII therefore acquire the ability to influence surrounding Leydig cells when they contain step 19 spermatids. It remains to be shown whether this maturation step is due to inherent maturation of the Sertoli cells or if step 19 spermatids specifically modulate Sertoli cell function.     

Effect of seminiferous tubule size on hCG-induced regeneration of peritubular Leydig cells in hypophysectomized, EDS-treated rats

Following their selective destruction 3 weeks previously by administration of ethane dimethanesulphonate (EDS) the regenerative capacity of Leydig cells was assessed in relation to seminiferous tubule morphology in hypophysectomized adult rats administered 7 daily injections of 100 iu hCG. Total Leydig cell volume per testis in hCG-treated rats (30.2 ±3.2 μl, mean ± SEM) was significantly ( p <0.01) greater than in the testes of rats at 3 and 4 weeks after EDS-treatment (7.6 ± 0.7 and 22.7 ± 1.4 μl, respectively). Regeneration of Leydig cells in hCG-treated rats significantly ( p <0.05) favoured peritubular locations (18.6 ± 2.8 μl/testis) compared to central or perivascular sites of origin (11.6 ± 1.2 μl/testis). Partial restoration of spermatogenesis occurred in hCG-treated rats (tubule diameters usually >250μm) and a significant inverse correlation was found between peritubular Leydig cell percentage, or total volume per testis, and the volumetric proportion of seminiferous tubules ( r =-0.94, p <0.001) or the seminiferous epithelium ( r =-0.73 to -0.79, p <0.05–0.01). No significant ( p >0.4–0.9) correlation existed between centrally-regenerated Leydig cells and these parameters. The results show that in response to hCG stimulation, Leydig cells are more likely to develop around smaller seminiferous tubules, suggesting that hCG alone cannot mimic the expected pattern of Leydig cell regeneration (central and peritubular origins) which occurs during normal sexual maturation or at 3–4 weeks after EDS treatment. It is concluded that other factors, possibly FSH, are required for typical Leydig cell development which in turn may be influenced by local cellular growth factors originating from either the seminiferous tubules or the adjacent intertubular tissue.     

Developmental and stage-specific expression of Smad2 and Smad3 in rat testis

Members of the transforming growth factor beta type (TGFbeta) superfamily and their receptors are expressed in the testis, and are believed to play important paracrine and autocrine roles during testicular development and spermatogenesis. The Smad proteins are downstream mediators for the family of TGFbeta growth factors. Smad2 and Smad3 are associated with both TGFbeta and activin signaling. However, very little is known about the expression and regulation of the Smad signaling proteins in the testis. In the present study, we have determined that Smad2 and Smad3 proteins are expressed in the postnatal testes of rats from 5 days to 60 days of age. Expression levels for both proteins are higher in young rats than in sexually mature rats. Smad2 and Smad3 messenger RNA levels parallel protein expression. Smad2 and Smad3 proteins are mainly localized in the cytoplasm of meiotic germ cells, Sertoli cells, and Leydig cells. Smad3 protein is localized to the nucleus of preleptotene to zygotene primary spermatocytes in young rats. Both proteins are expressed throughout all stages of the cycle of seminiferous tubules but are expressed at their lowest levels at stages VII-VIII in the seminiferous epithelium of adult rats. The presence of these downstream mediators in these cell types supports a role for TGFbeta and activin during spermatogenesis. The difference between the expression of Smad2 and Smad3 suggests that they may have different functions within the testis.     

Evaluation of the effect of selective germ cell depletion on subsequent spermatogenesis and fertility in the rat

Rats were treated with a single high dose of methoxy acetic acid (MAA; 650 mg/kg) specifically to deplete seminiferous tubules of pachytene and later spermatocytes. The impact of this selective depletion on subsequent spermatogenesis, sperm output and fertility was then evaluated at intervals ranging from 3 days to 10 weeks. Cauda epididymal sperm number was reduced progressively beyond 2 weeks post-treatment and reached a nadir at 5-6 weeks (28-34% of control values) before recovering progressively back to control levels at 10 weeks. Sperm motility was reduced significantly at 4-7 weeks post-treatment with a nadir at 6 weeks (35% of control values). Thus, at 5-6 weeks after MAA treatment, motile sperm output was reduced by 82-88%. Despite these changes, there was little evidence for infertility in the majority of treated males during a serial mating trial. Evaluation of seminiferous tubule morphology combined with germ cell counts at stage VII of the spermatogenic cycle confirmed that, initially, MAA induced the specific loss of pachytene and later spermatocytes at all stages other than early to mid stage VII. Maturation depletion of germ cells at later intervals was consistent with the initial effects of MAA, although at 21 days post-treatment a number of unpredicted (? secondary) changes in spermatogenesis were observed. These were (a) a reduction in number of pachytene spermatocytes at late stage VII/early stage VIII, (b) retention of sperm at stages IX-XIV, and (c) increased degeneration of pachytene spermatocytes and round spermatids at stage VII and of secondary spermatocytes at stages XIV-I. Whilst none of these changes was severe, together they probably accounted for the unexpectedly prolonged drop in sperm output. It is concluded that whilst deleterious changes in spermatogenesis may occur secondarily following MAA treatment, for the most part spermatogenesis proceeds normally and fertility is largely maintained despite a massive but transient decrease in sperm output.     

睾丸细胞生物学研究进展

睾丸是男性生殖腺,由生精小管和间质构成。生精小管主要由生精细胞和支持细胞组成,是精子发生场所;间质中主要是间质细胞,间质细胞合成与分泌雄激素。本文介绍睾丸3种细胞的发育分化,以及成年期睾丸细胞的结构和生物学研究进展。     

Spermatogenesis in the aged--a borderland between normal and pathologic anatomy

Aging of the testis is a normal physiological process, which gradually proceeds with increasing age. Under normal conditions, an abrupt breaking off the spermatogenetic and hormonal functions of the testis does not occur. Already in the testis of every adult fertile man single degenerating germ cells are recognizable, the occurrence of which is understood as physiological germ cell loss. In men, older than 65 years, further degenerative changes of the germ cells and of the germinal epithelium regularly can be found, which have negative effects on the spermatogenetic activity of the germinal epithelium. These changes concern disturbances of the kinetics of spermatogenesis, disturbances of spermatogoniogensis and of meiosis, malformations of the spermatids, the release of immature germ cells from the germinal epithelium, the concentration of lipids within the Sertoli cells, the appearance of diverticles of the seminiferous tubules and possibly also atrophy of seminiferous tubules. In the course of regular testicular aging these degeneration phenomena can be observed to a relatively small extent diffusely distributed in the testis and exhibiting individual differences. A phatological alteration of the testicular tissue is under consideration as soon as a definitive pattern of damage predominates in the whole organ or when a focal degeneration of testicular tissue has appeared. The borderland between normal and pathological anatomy of testis tissue during aging is characterized.