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The association between alcohol-induced disorders of human spermatogenesis and glutathione S-transferase-M1 genotype was investigated in an autopsy study comprising 271 subjects, including interviews with relatives or close acquaintances on the alcohol consumption of the deceased. Of the 50 moderate drinking men (reported mean daily alcohol consumption < 40 g), 21 (42.0%) had normal spermatogenesis, whereas 24 men (48.0%) had partial, and five (10.0%) complete arrest of spermatogenesis. Of the 21 men with normal spermatogenesis, nine (42.9%) had GST M1 'null' genotype, while this genotype was found in 13 (44.8%) of the 29 men with partial or complete spermatogenic arrest. Of 212 heavy-drinking men (reported mean daily alcohol consumption > 80 g), only 45 (21.2%) had normal spermatogenesis, whereas 77 (36.3%) had partial spermatogenic arrest. Complete arrest of spermatogenesis was found in 81 men (38.2%) and nine men had Sertoli-cell-only syndrome (4.2%). Of the 45 heavy drinkers with normal spermatogenesis, 27 (60%) men had GST M1 'null' genotype (OR 2.7 with 95% confidence intervals: 1.0-4.0, when compared to those with disorders of spermatogenesis). The frequency of GST M1 'null' genotype in heavy drinkers with normal spermatogenesis also differed from that of corresponding moderate drinkers, whereas the frequency of GST M1 'null' genotype in heavy drinkers with disorders of spermatogenesis was similar to moderate drinkers with or without disorders of spermatogenesis. The finding that > 20% of men in the heavy-drinking group had normal spermatogenesis suggests individual variations in sensitivity to alcohol-induced disorders of this process. Heavy drinkers with GST M1 'null' genotype were slightly less prone to develop disorders of spermatogenesis. Thus, the GST M1 locus may be associated with susceptibility to develop alcohol-induced disorders of spermatogenesis.
Spermatogenesis is a process of division and differentiation by which spermatozoa are produced in seminiferous tubules. A measure of efficiency of spermatogenesis is the estimated number of spermatozoa produced per day per gram of testicular parenchyma. This measure is not influenced by species differences in testicular size; however, it is influenced by species differences in the numerical density of germ cells and in the life spans of these cells. Seminiferous tubules are composed of somatic cells (myoid cells and Sertoli cells), and germ cells (spermatogonia, spermatocytes, and spermatids). Activity of these three germ cells divide spermatogenesis into spermatocytogenesis, meiosis, and spermiogenesis, respectively. Spermatocytegenesis involves mitotic cell division to increase the yield of spermatogenesis and to produce stem cells and primary spermatocytes. Meiosis involves duplication and exchange of genetic material and two cell divisions that reduce the chromosome number and yield four spermatids. Spermiogenesis is the differentiation of spherical spermatids into mature spermatids which are released at the luminal free surface as spermatozoa. The spermatogenic cycle is superimposed on the three major divisions of spermatogenesis. Spermatogenesis and germ cell degeneration can be quantified from numbers of germ cells in various steps of development throughout spermatogenesis, and quantitative measures are related to number of spermatozoa in the ejaculate. Germ cell degeneration occurs throughout spermatogenesis; however, the greatest impact occurs during spermatocytogenesis and meiosis. Efficiency of spermatogenesis is related to the amount of germ cell degeneration, pubertal development, season of the year, and aging of humans and animals. Number of Sertoli cells and amount of smooth endoplasmic reticulum of Leydig cells (but not Leydig cell number) are related to efficiency of spermatogenesis. In humans, efficiency of spermatogenesis is reflected in number of spermatogenic stages per cross-section and number of missing generations within each stage; however, the arrangement of stages along the tubular length does not reflect differences in the efficiency of spermatogenesis. In short, spermatogenesis involves both mitotic and meiotic cell divisions and an unsurpassed example of cell differentiation in the production of the spermatozoon, and daily sperm production per g parenchyma is a measure of its efficiency.
We showed previously that testosterone (T) alone could induce spermatogenesis and produce normally fertile spermatozoa in the absence of circulating gonadotropins. These studies used the hpg mouse, which is characterized by a congenital gonadotrophin deficiency due to a major deletion in the GnRH gene. Administering T by a subdermal implant of a SILASTIC brand tube impregnated with crystalline T showed that the androgenic requirement for full induction of spermatogenesis was a 1-cm length implant. Using this unique model of spermatogenesis without gonadotropins, we have now investigated the quantitative requirement for androgens to maintain spermatogenesis by testing the hypothesis that the androgenic threshold required for induction and maintenance of spermatogenesis are the same. Spermatogenesis was induced in homozygous hpg mice by T administration for 6 weeks. The first experiment determined the time-course of the regression of spermatogenesis after removal of the T-impregnated SILASTIC brand implant. Elongated spermatids were absent by 3 weeks and testicular weight regression was maximal by 4 weeks after androgen withdrawal. The second experiment examined the effects on maintenance of spermatogenesis of reducing the T dose. After full induction of spermatogenesis in homozygous hpg mice, the T implants were replaced with a range of smaller size T-impregnated SILASTIC brand implants for a further 4 weeks. All androgen-sensitive end-points (testis weight, tubular, and luminal diameters, round spermatids) were fully maintained with T implants of 0.06 cm and elongated spermatids with T implants of 0.25 cm. A further experiment showed that at very low T doses (0.06, 0.125 cm) the T effects observed at 4 weeks were maintained at 6 and 11 weeks duration. We conclude that the androgenic threshold to maintain spermatogenesis in the mouse is an order of magnitude lower than the threshold required for inducing spermatogenesis. This distinction suggests that the mechanism of action of testosterone in inducing spermatogenesis may involve regulation of a genetic switch to complete meiosis, whereas the maintenance involves a different locus of action. These findings suggest that further studies of androgen-dependent meiotic genes may be central to understanding the regulation and molecular basis of androgen-driven induction and maintenance of spermatogenesis.
UNLABELLED: The current experiment examined the effects of exogenous testosterone (T) on spermatogenesis in rats with spinal cord injury (SCI) and their relationship with the cellular distribution of a cyclic AMP-responsive element modulator (CREM) in testicular cells. Implantation of T-filled Silastic capsules (TCs, 1-20 cm) resulted in dose-dependent, biphasic changes in testicular T levels and spermatogenesis in SCI rats. However, dose responsiveness of spermatogenesis to exogenous T in SCI rats differed from that in sham control rats. Specifically, implantation of 2-cm TCs enhanced the effects of SCI on spermatogenesis, resulting in total regression of the seminiferous epithelium. Although 3-cm TCs maintained complete spermatogenesis in sham control rats, this regimen failed to support complete spermatogenesis in SCI rats. Although complete spermatogenesis was maintained in SCI rats given 5-20-cm TC implants, various abnormalities persisted. Cellular distribution of CREM remained normal in SCI rats but was altered in those SCI rats that received 3- or 5-cm TC implants. Such effects were associated with reduced CREM proteins in testicular tissues. These results were consistent with altered cAMP signaling and its regulation in testicular cells after SCI and provided possible mechanistic explanations for the effects of SCI on spermatogenesis. CONCLUSION: SCI resulted in changes in the responsiveness of spermatogenesis to exogenous T. These effects were associated with altered cAMP/CREM signaling in testicular cells. Further studies, including a study of the relationship between serum T levels and normalcy of sperm functions and the role of neural-endocrine interactions in mediating the effects of SCI on spermatogenesis and sperm function, are needed so that therapeutic regimens can be designed for clinical use.
Efficiency of spermatogenesis is the estimated number of spermatozoa produced per day per gram of testicular parenchyma. Spermatogenesis is the process of cell division and cell differentiation by which spermatozoa are produced in testes. Efficiency of spermatogenesis is influenced by species differences in the numerical density of germ cell nuclei and in the life span of these cells. Activities of spermatogonia, spermatocytes, and spermatids partition spermatogenesis into three major divisions (spermatocytogenesis, meiosis, and spermiogenesis, respectively). Spermatocytogenesis involves mitotic germ cell division to produce stem cells and primary spermatocytes. Meiosis involves duplication of chromosomes, exchange of genetic material, and two cell divisions that reduce the chromosome number and yield four spermatids. In spermiogenesis, spherical spermatids differentiate into mature spermatids which are released in the lumen of seminiferous tubules as spermatozoa. Spermatogenesis and germ cell degeneration can be quantified from numbers of germ cells in various developmental steps throughout spermatogenesis. Germ cell degeneration occurs throughout spermatogenesis; however, the greatest impact occurs during spermatocytogenesis and meiosis. There are species and seasonal influences on the developmental steps in spermatogenesis at which germ cell degeneration occurs. Number of Sertoli cells, amount of smooth endoplasmic reticulum of Leydig cells, and the number of missing generations of germ cells within the spermatogenic stage of the cycle influence efficiency of spermatogenesis. Efficiency of spermatogenesis is influenced to the amount of germ cell degeneration, pubertal development, season of the year, and aging of humans and animals.
Subfertility affects about 15% of all couples. Assessment of spermatogenesis has a central role in the evaluation of the subfertile couple. Classical markers of spermatogenesis, such as semen analysis, testicular biopsy and endocrine evaluation all have their diagnostic limitations. There is a clear need for accurate additional markers of spermatogenesis. Recently, the serum inhibin B level has emerged as a sensitive endocrine marker of spermatogenesis. This paper summarises the pros and cons of different markers of spermatogenesis, with specific focus on serum inhibin B. The serum inhibin B level has been shown to be associated with classical markers of spermatogenesis, particularly testicular histology, and to be the most accurate endocrine marker of spermatogenesis. A subnormal serum inhibin B level clearly reflects disturbed spermatogenesis. Before puberty, when no spermatogenesis takes place, inhibin B is a marker of testicular integrity. Clinical applications of serum inhibin B in childhood and adulthood are given, and a view on future directions and research is presented. The serum inhibin B level has proven to be valuable in the evaluation of spermatogenesis, and holds a promise for further research.
The association between alcohol-induced disorders of human spermatogenesis and four restriction fragment polymorphisms (DraI, MspI, PstI and RsaI) of the cytochrome P450 2E1 gene was investigated in an autopsy study on 254 men. Acquaintances were interviewed and the mean daily alcohol consumption of the subjects was calculated on the basis of the interviews. Spermatogenesis score and testicular morphology were assessed by light-microscopy, and cytochrome 2E1 polymorphic genotypes were determined using the polymerase chain reaction. Of the 204 heavy-drinking men, 42 (20.6%) men had normal spermatogenesis (p < 0.001, compared to moderate drinkers). Partial spermatogenic arrest was observed in 76 (37.3%) men and complete spermatogenic arrest in 79 (38.7%) men (p < 0.001, compared to moderate drinkers), whereas seven men (3.4%) had Sertoli cell only syndrome. The overall allelic frequencies for the common and rare polymorphic alleles were 0.98 and 0.02 (MspI) and 0.99 and 0.01 (PstI and RsaI), respectively. No associations between heterozygosity in the MspI, PstI or RsaI loci, or the allelic frequencies of common and rare alleles, and disorders of spermatogenesis were observed. The allelic frequencies for the common and rare polymorphic alleles in the DraI locus were 0.90 and 0.10, respectively. No significant difference was observed, either among moderate or heavy drinkers, in the frequency of the rare allele between men with disorders of spermatogenesis and those with normal spermatogenesis in the respective group, although men with disorders of spermatogenesis in general had a slightly lower frequency of the rare allele when compared to those with normal spermatogenesis. In conclusion, we were unable to demonstrate a significant association between any polymorphisms in the CYP2E1 gene and disorders of spermatogenesis. RsaI, MspI and PstI polymorphisms were extremely rare in our population and could thus possibly be excluded as reasons for genetic susceptibility to disorders of spermatogenesis in our series.
This study investigated whether neonatal exposure of male rats to estrogenic compounds altered pubertal spermatogenesis (days 18 and 25) and whether the changes observed resulted in long-term changes in testis size, mating, or fertility (days 90-100). Rats were treated neonatally with a range of doses (0.01-10 microg) of diethylstilbestrol (DES; administered on alternate days from days 2-12), a high dose of octylphenol (OP; 2 mg administered daily from days 2-12) or bisphenol A (Bis-A; 0.5 mg administered daily from days 2-12), or vehicle, while maintained on a standard soy-containing diet. The effect on the same parameters of rearing control animals on a soy-free diet was also assessed as was the effect of administering such animals genistein (4 mg/kg/day daily from days 2-18). Testis weight, seminiferous tubule lumen formation, the germ cell apoptotic index (apoptotic/viable germ cell nuclear volume), and spermatocyte nuclear volume per unit Sertoli cell nuclear volume were used to characterize pubertal spermatogenesis. Compared with (soy-fed) controls, DES administration caused dose-dependent retardation of pubertal spermatogenesis on day 18, as evidenced by decreases in testis weight, lumen formation, and spermatocyte nuclear volume per unit Sertoli cell and elevation of the germ cell apoptotic index. However, the two lowest doses of DES (0.1 and 0.01 microg) significantly increased spermatocyte nuclear volume per unit Sertoli cell. Similarly, treatment with either OP or Bis-A significantly advanced this and some of the other aspects of pubertal spermatogenesis. Maintenance of control animals on a soy-free diet also significantly advanced lumen formation and spermatocyte nuclear volume per unit Sertoli cell compared with controls fed a soy-containing diet. Administration of genistein reversed the stimulatory effects of a soy-free diet and significantly retarded most measures of pubertal spermatogenesis. In general, plasma FSH levels in the treatment groups changed in parallel to the spermatogenic changes (reduced when pubertal spermatogenesis retarded, increased when pubertal spermatogenesis advanced). By day 25, although the changes in FSH levels largely persisted, all of the stimulatory effects on spermatogenesis seen on day 18 in the various treatment groups were no longer evident. In adulthood, testis weight was decreased dose dependently in rats treated neonatally with DES, but only the lowest dose group (0.01 microg) showed evidence of mating (3 of 6) and normal fertility (3 litters). Animals treated neonatally with OP or Bis-A had normal or increased (Bis-A) testis weights and exhibited reasonably normal mating/fertility. Animals fed a soy-free diet had significantly larger testes than controls fed a soy-containing diet, and this difference was confirmed in a much larger study of more than 24 litters, which also showed a significant decrease in plasma FSH levels and a significant increase in body weight in the males kept on a soy-free diet. Neonatal treatment with genistein did not alter adult testis weight, and although most males exhibited normal mating and fertility, a minority did not mate or were infertile. It is concluded that 1) neonatal exposure of rats to low levels of estrogens can advance the first wave of spermatogenesis at puberty, although it is unclear whether this is due to direct effects of the estrogen or to associated elevation of FSH levels; 2) the effect of high doses of OP and Bis-A on these processes is essentially benign; and 3) the presence or absence of soy or genistein in the diet has significant short-term (pubertal spermatogenesis) and long-term (body weight, testis size, FSH levels, and possibly mating) effects on males.
Testosterone (T) is an absolute requirement for spermatogenesis and is supplied by mature Leydig cells stimulated by LH. We previously showed in gonadotropin-deficient hpg mice that T alone initiates qualitatively complete spermatogenesis bypassing LH-dependent Leydig cell maturation and steroidogenesis. However, because maximal T effects do not restore testis weight or germ cell number to wild-type control levels, additional Leydig cell factors may be involved. We therefore examined 1). whether chronic hCG administration to restore Leydig cell maturation and steroidogenesis can restore quantitatively normal spermatogenesis and testis development and 2). whether nonandrogenic Leydig cell products are required to initiate spermatogenesis. Weanling hpg mice were administered hCG (0.1-100 IU i.p. injection three times weekly) or T (1-cm subdermal Silastic implant) for 6 weeks, after which stereological estimates of germinal cell populations, serum and testicular T content, and testis weight were evaluated. Human CG stimulated Leydig cell maturation and normalized testicular T content compared with T treatment where Leydig cells remained immature and inactive. The maximal hCG-induced increases in testis weight and serum T concentrations were similar to those for T treatment and produced complete spermatogenesis characterized by mature, basally located Sertoli cells (SCs) with tripartite nucleoli, condensed haploid sperm, and lumen development. Compared with T treatment, hCG increased spermatogonial numbers, but both hCG and T had similar effects on numbers of spermatocytes and round and elongated spermatids per testis as well as per SC. Nevertheless, testis weight and germ cell numbers per testis and per SC remained well below phenotypically normal controls, confirming the involvement of non-Leydig cell factors such as FSH for quantitative normalization of spermatogenesis. We conclude that hCG stimulation of Leydig cell maturation and steroidogenesis is not required, and that T alone mostly replicates the effects of hCG, to initiate spermatogenesis. Because T is both necessary and sufficient for initiation of spermatogenesis, it is likely that T is the main Leydig cell secretory product involved and that additional LH-dependent Leydig cell factors are not essential for induction of murine spermatogenesis.
Under fresh-water cultivation conditions, spermatogenesis in the Japanese eel is arrested at an immature stage before initiation of spermatogonial proliferation. A single injection of human chorionic gonadotropin can, however, induce complete spermatogenesis, which suggests that spermatogenesis-preventing substances may be present in eel testis. To determine whether such substances exist, we have applied a subtractive hybridisation method to identify genes whose expression is suppressed after human chorionic gonadotropin treatment in vivo. We found one previously unidentified cDNA clone that was downregulated by human chorionic gonadotropin, and named it 'eel spermatogenesis related substances 21' (eSRS21). A homology search showed that eSRS21 shares amino acid sequence similarity with mammalian and chicken Müllerian-inhibiting substance. eSRS21 was expressed in Sertoli cells of immature testes, but disappeared after human chorionic gonadotropin injection. Expression of eSRS21 mRNA was also suppressed in vitro by 11-ketotestosterone, a spermatogenesis-inducing steroid in eel. To examine the function of eSRS21 in spermatogenesis, recombinant eSRS21 produced by a CHO cell expression system was added to a testicular organ culture system. Spermtogonial proliferation induced by 11-ketotestosterone in vitro was suppressed by recombinant eSRS21. Furthermore, addition of a specific anti-eSRS21 antibody induced spermatogonial proliferation in a germ cell/somatic cell co-culture system. We conclude that eSRS21 prevents the initiation of spermatogenesis and, therefore, suppression of eSRS21 expression is necessary to initiate spermatogenesis. In other words, eSRS21 is a spermatogenesis-preventing substance.
The testes of busulfan-treated immunodeficient mice receiving seminiferous tubule injections of testis cells from rats were examined by light and electron microscopy. The presence of active rat spermatogenesis was verified by criteria that are known to characterize spermatogenic cells of this species. In addition, spermatogenesis from the mouse was identified as taking place in some seminiferous tubules as the result of reinitiation of spermatogenesis after busulfan treatment. Rat spermatogenesis in mouse seminiferous tubules showed the generally recognized associations of cells known to characterize stages of spermatogenesis of the rat. The Sertoli cells associated with rat spermatogenesis were identified ultrastructurally as being of mouse origin. Thus, rat spermatogenesis, which has a cycle length that is 50% longer than mouse spermatogenesis, can proceed among mouse Sertoli cells, which supposedly exert much shorter cyclic influences in concert with mouse germ cell development. Studies are needed to determine if the timing of rat spermatogenesis is controlled by the germ cells or the Sertoli cells. These observations are considered preliminary since a thorough study of somatic-germ cell relationships was not undertaken. It is concluded that a mouse Sertoli cell in the environment provided by the mouse testis can produce both mouse and rat gametes.
Spermatogenesis is a process of division and differentiation by which spermatozoa are produced in seminiferous tubules. Seminiferous tubules are composed of somatic cells (myoid cells and Sertoli cells) and germ cells (spermatogonia, spermatocytes, and spermatids). Activities of these three germ cells divide spermatogenesis into spermatocytogenesis, meiosis, and spermiogenesis, respectively. Spermatocytogenesis involves mitotic cell division to increase the yield of spermatogenesis and to produce stem cells and primary spermatocytes. Meiosis involves duplication and exchange of genetic material and two cell divisions that reduce the chromosome number to haploid and yield four spermatids. Spermiogenesis is the differentiation without division of spherical spermatids into mature spermatids which are released from the luminal free surface as spermatozoa. The spermatogenic cycle (12.2 days in the horse) is superimposed on the three major divisions of spermatogenesis which takes 57 days. Spermatogenesis and germ cell degeneration can be quantified from numbers of germ cells in various steps of development throughout spermatogenesis, and quantitative measures are related to number of spermatozoa in the ejaculate. Germ cell degeneration occurs throughout spermatogenesis; however, the greatest seasonal impact on horses occurs during spermatocytogenesis. Daily spermatozoan production is related to the amount of germ cell degeneration, pubertal development, season of the year, and aging. Number of Sertoli cells and amount of smooth endoplasmic reticulum of Leydig cells and Leydig cell number are related to spermatozoan production. Seminiferous epithelium is sensitive to elevated temperature, dietary deficiencies, androgenic drugs (anabolic steroids), metals (cadmium and lead), x-ray exposure, dioxin, alcohol, and infectious diseases. However, these different factors may elicit the same temporary or permanent response in that degenerating germ cells become more common, multinucleate giant germ cells form by coalescence of spermatocytes or spermatids, the ratio of germ cells to Sertoli cells is reduced, and spermatozoan production is adversely affected. In short, spermatogenesis involves both mitotic and meiotic cell divisions and an unsurpassed example of cell differentiation in the production of the spermatozoon. Several extrinsic factors can influence spermatogenesis to cause a similar degenerative response of the seminiferous epithelium and reduce fertility of stallions.
PURPOSE: Cryptorchidism is an adverse condition of spermatogenesis in many mammals. Surgical cryptorchidism in rats lasting more than a few weeks is so detrimental that spermatogenesis cannot be completely recovered even after orchiopexy. We evaluated the efficacy of the high dose gonadotropin-releasing hormone (Gn-RH) agonist leuprorelin acetate on damaged spermatogenesis in rat cryptorchid testes. MATERIALS AND METHODS: Male Fisher rats were divided into 2 groups of 6 each and bilateral cryptorchidism was artificially produced. Five weeks later all rats underwent bilateral orchiopexy. One group served as the control, while the other received Gn-RH agonist injections at orchiopexy and 4 weeks later. The animals were sacrificed 15 weeks after orchiopexy. The weight of the body, testis and epididymis was measured and the histology of spermatogenesis was examined. For statistical analysis the Student t test was applied. RESULTS: Testes in the Gn-RH group rats showed significant recovery of spermatogenesis up to complete spermatozoa formation, while those in control rats remained almost degenerated. The mean incidence of seminiferous tubules with recovered spermatogenesis plus or minus standard deviation was significantly higher in the Gn-RH than in the control group (87.8% +/- 6.0% versus 12.5% +/- 7.7%, p <0.001). CONCLUSIONS: Administering the high dose Gn-RH agonist leuprorelin acetate after orchiopexy greatly enhanced the recovery of spermatogenesis in rats. This finding is in accordance with other recent reports that treatment with Gn-RH analogues promotes the regeneration of once damaged spermatogenesis. On the other hand, these findings may cause one to question supplementation therapy now used in regular practice to boys with cryptorchidism.
Our previous studies have demonstrated that impaired spermatogenesis during the acute phase of spinal cord injury (SCI) is preceded by a transient (but significant) suppression of serum FSH, LH, and testosterone (T) concentrations. It is hypothesized that hormonal deprivation may impair Sertoli cell function, leading to the loss of spermatogonia, degeneration of spermatogenic cells, and eventual regression of the seminiferous epithelium. The current study examined the efficacy of exogenous T and FSH in the maintenance of spermatogenesis and Sertoli cell functions in SCI rats. Implantation of T capsules (TC, 2 x 5 cm) attenuated some of the spermatogenic lesions and maintained qualitatively complete spermatogenesis in all SCI rats 4 weeks after the surgery. In contrast, daily injections of 0.1 U of FSH alone, or in combination with TC implants, paradoxically enhanced the regression of spermatogenesis in SCI rats. At this time, the numbers of Aal, A1, and B spermatogonia and preleptotene spermatocytes in SCI rats have decreased by 25-30%. Though not prevented by TC implants, the decrease in Aal and A1 spermatogonia was attenuated by FSH alone but was further enhanced when FSH-treated rats also received TC implants. The intratesticular T concentration in untreated and FSH-treated SCI rats was not different from that of sham control rats, but it decreased by more than 95% in those SCI rats given TC implants alone. These results demonstrate that impairment of spermatogenesis during the acute phase of SCI is not related to the availability of FSH and/or T. Northern blot analysis revealed an increase in androgen receptor messenger RNA (mRNA) in the testis of SCI rats; this increase was prevented by TC implants but persisted when FSH was also given. In contrast, the levels of FSH-receptor, androgen binding protein, and transferrin mRNA were not affected by SCI but were significantly higher in those SCI rats given FSH alone or in combination with TC. TC implants alone suppressed mRNA levels of transferrin in testes of SCI rats, without concomitant change in those for FSH-receptor and ABP. The changes in Sertoli cell responses to FSH and T, and perhaps other hormones, may alter signal events elicited by these hormones, thus contributing to abnormal epithelial environments and regression of spermatogenesis. Maintenance of spermatogenesis in SCI rats by exogenous T suggests the feasibility of using exogenous hormones to impede the detrimental effects of SCI on spermatogenesis. This approach may have clinical applicability for the preservation of spermatogenic functions in SCI men.
Recently, we reported that changes in spermatogenesis in adult rats during acute phase (within 2 weeks) of spinal cord injury (SCI) were associated with a suppression of pituitary-testis hormone axis, and these effects mimic those that occur after hormone deprivation. In this study, we examined the long-term (>4 weeks) effects of SCI on spermatogenesis and its recovery. Results of this study reveal that while serum follicle stimulating hormone, luteinizing hormone, and testosterone levels in SCI rats recovered within 1 month after the injury, their spermatogenesis continued to regress. By 3 months, spermatogenesis in 70% of SCI rats has totally regressed, characterized by the absence of proliferating spermatogonia; these effects could not be prevented by an otherwise effective regimen of testosterone treatment. Sertoli cells in the regressed seminiferous tubules exhibited unusual behavior, characterized by the formation of multiple cell layers and/or aggregates that extended into the tubular lumen. Active spermatogenesis was observed in nine of the 19 SCI rats by 6 months, seven of which had complete spermatogenesis, but with persisting abnormalities. These results demonstrate that SCI results in total, but reversible, regression of spermatogenesis. Failure to prevent such effects by an otherwise effective exogenous testosterone regimen suggests that non-endocrine factors are involved in the SCI effects on spermatogenesis. The unusual Sertoli cell localization in the regressed testes may have been triggered by the loss of proliferating spermatogonia and may be involved in subsequent spermatogenic recovery.
Spermatogenesis cell apoptosis is a very complex process, which needs many molecules to take part in the programmable death of cells in testis. At present, research of apoptosis for spermatogenesis cell is at the primary step. It is very important to clone spermatogenesis cell apoptosis related genes and spermatogenesis genes in testis. Applying the bioinformatics and experiment technique, we have cloned human and mouse novel gene cDNA sequences--human testis and spermatogenesis cell apoptosis related gene 1 (TSARG1) and mouse testis and spermatogenesis cell apoptosis related gene 1(Mtsarg1) from human and mouse testis cDNA library respectively, using a cDNA fragment (GenBank accession number: BE644538) as an electronic probe, which was significantly changed in expression in cryptorchidism. The GeneBank accession numbers of Mtsarg1 and TSARG1 are AF399971 and AY032925 (NM_139073), respectively. The Mtsarg1 has a 55% identity and 61% similarity with TSARG1 at the amino acid level, which did not share significant homology with any other known protein in databases. The full-length cDNA of TSARG1 gene is 973 bp, including 549 bp open reading frame(ORF) and coding 183 amino acids, whereas the full-length cDNA of Mtsarg1 gene is 1103 bp, including 576 bp ORF and coding 192 amino acids. The predicted molecule weight of TSARG1 is 19948.61 Dolton, and the deduced iso-electric point is 10.24, whereas the Mtsarg1 is 20875.93 and is 9.83, being alkaline proteins. RT-PCR analysis showed that Mtsarg1 was expressed significantly in testis and faintly in epididymis in the ten tissues of testis, ovary, spleen, kidney, lung, heart, brain, epididymis, liver and skeletal muscle in mouse, while it wasn't expressed in the other eight tissues. Therefore, our results suggested that Mtsarg1 and TSARG1 would be pay potential roles in spermatogenesis cell apoptosis or spermatogenesis.
OBJECTIVES: The pathologic complexity of the testicular tumor makes it difficult to demonstrate exactly the relationship between the impaired spermatogenesis in patients with a testicular tumor and the serum level of the human chorionic gonadotropin beta subunit (beta-hCG). Therefore, we performed quantitative evaluation of spermatogenesis in ipsilateral and contralateral testicular tissues of seminoma to simplify the relation pathologically and endocrinologically and to demonstrate the exact correlation between spermatogenesis and serum beta-hCG levels. METHODS: Fifty-three biopsy specimens from ipsilateral and contralateral testicular tissues of seminoma were analyzed histologically. The quantitative evaluation of spermatogenesis was performed by the mean Johnsen's score count (MJSC). Beta-hCG expression in seminoma was examined immunohistochemically. Serum beta-hCG, testosterone, estradiol, luteinizing hormone, and follicle-stimulating hormone levels were analyzed before orchiectomy. RESULTS: A significant linear relationship (r = -0.82; P <0.005) was found between the serum level of beta-hCG and the MJSC in contralateral testicular tissues but not in ipsilateral ones, although the suppression of spermatogenesis was observed in both sides without suppression of luteinizing hormone and/or follicle-stimulating hormone production. CONCLUSIONS: A clearcut fall in the MJSC with an associated rise in the serum level of beta-hCG was demonstrated in the contralateral testicular tissues but not in the ipsilateral ones of seminoma. It seems most likely that serum beta-hCG suppresses spermatogenesis in both ipsilateral and contralateral testicular tissues without the suppression occurring through the hypothalamus-pituitary-gonadal system, and also that some less well recognized factors affect spermatogenesis, making the relation between serum beta-hCG and MJSC obscure in ipsilateral testicular tissues.