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PubMedDate not supplied

The effects of recombinant FSH on testosterone-induced spermatogenesis in gonadotrophin-deficient (hpg) mice.

In order to clarify the mechanism of synergism between follicle-stimulatory hormone(FSH) and testosterone (T) in the hormonal regulation of spermatogenesis, we studied the effects of recombinant human FSH (rhFSH) on the induction of spermatogenesis by testosterone in congenitally gonadotropin-deficient hpg mice. Weanling (day 21) homozygous hpg mice were administered daily subcutaneous injections of 1, 5, or 10 IU of rhFSH alone or in combination with a subdermal testosterone implant until day 70 of age. Spermatogenesis was quantitated by stereological estimation of germ cell populations and Sertoli cells as well as measurement of diameter of seminiferous tubules and their lumina in perfusion-fixed testes and by counting homogenization-resistant condensed testicular spermatids. Recombinant human FSH alone increased the absolute numbers of spermatogonia (x3.5-fold) and spermatocytes (x3-fold) compared with untreated hpg mice but did not significantly increase Sertoli cell numbers or form any condensed spermatids or tubular lumen. Relative to Sertoli cell numbers, rhFSH alone increased populations of spermatogonia (x2-fold) and spermatocytes (x2-fold). The addition of T to rhFSH further increased the absolute numbers of spermatogonia (x5-fold) and spermatocytes (x3.5-fold) compared with untreated hpg mice as well as increasing tubular diameter and forming tubular lumina. In addition administration of T allowed the completion of spermatogenesis in the presence of intratesticular T levels that were approximately 2% of non-hpg controls. All effects of the FSH + T combination were however no greater than the effects of the equivalent dose of T alone. The present study therefore indicates that rhFSH alone increases proliferation of premeiotic spermatogenic cells but has no effect on the completion of spermiogenesis or on Sertoli cell maturation. Furthermore we were unable to identify any additive effects of FSH with T in the hormonal regulation of spermatogenesis in the hpg mouse. This suggests that FSH or T both may stimulate initial spermatogenic development, but only T can complete spermiogenesis.

Animals↗
PubMedDate not supplied

Decreased spermatogenesis as the result of an induced autoimmune reaction directed against the gonadotropin receptors in male rats.

The presence of luteinizing hormone (LH) and testosterone is considered critical for the maintenance of spermatogenesis in the rat. However, the role and importance of follicle-stimulating hormone (FSH) in the initiation and maintenance of spermatogenesis has been a subject of debate for some time. The objective of this study was to examine the role of FSH and LH in vivo in the developing and adult rat by inducing an autoimmune reaction against the receptors to these gonadotropins. Sperm numbers were reduced in animals immunized against either the FSH or LH receptor (FSHR/LHR). In animals immunized against both FSHR and LHR there was also a significant reduction in sperm number although spermatogenesis was never completely ablated. These results were seen in male rats immunized either prepubertally (18 days of age) or as adults (80 days of age). To examine the requirements for FSH in early postnatal-testicular development, pregnant females were also immunized against either FSHR, LHR, or both of the receptors, and the male offspring were examined at 30 days of age. Again, germ-cell number was decreased with the greatest effect in those pups whose mothers were immunized against both FSHR and LHR. Radioligand-receptor-binding assays revealed that the antibody produced in the rats against FSHR was able to compete with FSH for binding sites in receptor-membrane preparations. Therefore, the mechanism of disruption of spermatogenesis is probably due to suppression of hormone to receptor binding. The results of this study support a role for FSH in spermatogenesis not only during neonatal and early postnatal development but also in the adult animal.

Amino Acid Sequence↗
PubMed1997

[Current aspects of hormone diagnosis in andrology--predictive values for the preservation of spermatogenesis].

The occurrence of hormonal disorders in 1.4 to 9.7% of the patients of andrology units justify a corresponding hormone analysis. Besides helping to make the differential-diagnosis of a disease hormone results are important for the description of preservation of spermatogenesis in cases of aspermia or azoospermia. Indications of a rest-spermatogenesis or a spermatozoon-pool could be crucial for assisted reproduction. Spermatological and testis-histological data of 2 independent collectives (n1 = 138; n2 = 110) were correlated with basal levels of FSH, LH, PRL, T, free T, and E2. Serum FSH appears with a sensitivity of 88.8% and a specification of 94.1% as good, but not absolutely certain discriminator of preserved or disturbed spermatogenesis. The inclusion of testis volume improves the diagnostic reliability only negligibly--the critical size is 16 ml. Because of its low diagnostic sensitivity the serum LH alone gives not much information but it can indicate together with serum testosterone causally relevant disorders in androgen metabolism (i.e. androgen resistance syndrome. Klinefelter-syndrome). PRL, T, free T, and E2 gave no conclusion of occurrence of disturbed or preserved spermatogenesis. For indication of performing testis biopsy because of diagnosis and therapeutic considerations further factors of spermatogenesis are required.

Adult↗
PubMed2000

Gossypol blood levels and inhibition of spermatogenesis in men taking gossypol as a contraceptive. A multicenter, international, dose-finding study.

The safety and efficacy of gossypol continues to be controversial. The aim of this study was to evaluate gossypol as a contraceptive pill for men at doses lower than those previously prescribed and in men from various ethnic origin. A total of 151 men from Brazil, Nigeria, Kenya, and China were divided into two groups. Both groups received 15 mg gossypol/day for 12 or 16 weeks to reach spermatogenesis suppression. Subjects were then randomized to either 7.5 or 10 mg/day for 40 weeks. In addition, 51 men were enrolled as a control group. In all, 81 subjects attained spermatogenesis suppression. Only one man discontinued treatment because of tiredness. Potassium levels fluctuated within the normal range. FSH increased consistently. Testicular volume decreased, but after discontinuation, values returned to levels not statistically different from admission. Of 19 subjects on the 7.5 mg/day dose group, 12 recovered sperm counts >20 million/mL within 12 months of discontinuing gossypol. In the 10 mg/day group, sperm counts recovered in only 10 of 24 subjects. Eight of the 43 patients remained azoospermic 1 year after stopping gossypol. All men diagnosed with varicocele failed to reverse spermatogenesis suppression. Gossypol blood levels indicated that sperm suppression occurs independently of concentration, whereas spermatogenesis recovery appears to be concentration-dependent. Gossypol may become a medical alternative to surgical vasectomy when the delay in onset of infertility is acceptable. When taken for 1 year, gossypol causes no reduction in sexual desire or frequency of intercourse. The possibility of reversal, occurring in 51% of the men on this regimen within 1 year after stopping gossypol, is an advantage of this compound as compared with surgical sterilization in many parts of the world.

Adult↗
PubMed1996

Biochemical markers of early and late spermatogenesis: relationship between the lactate dehydrogenase-X and creatine kinase-M isoform concentrations in human spermatozoa.

As part of our research program on biochemical markers of sperm maturity, we have studied sperm creatine kinase (CK) and lactate dehydrogenase (LDH) concentrations and the isoform ratios of the CK-M [% CK-M/(CK-M + CK-B)] and LDH-X [% LDH-X/(LDH-X + LDH-a)] in 50 oligospermic and 95 normospermic men [corrected]. Because the synthesis of LDH-X is initiated in early spermatogenesis, and that of CK-M commences in late spermiogenesis simultaneously with cytoplasmic extrusion, we proposed two working hypotheses:(1) LDH and CK concentrations reflect the retained cytoplasm in sperm, thus the activities of both enzymes will be related and will be higher in oligospermic specimens, which have a higher incidence of immature spermatozoa; and (2) because in normally developed sperm both LDH-X and CK-M are present, there will be a correlation between LDH-X and CK-M ratios in the mature sperm populations. However, among men with immature sperm samples with late spermiogenetic defect and diminished CK-M ratios, there will be two groups: one which completed spermatogenesis prior to spermiogenetic failure (normal LDH-X and diminished CK-M ratios), and another group with defects in both spermatogenesis and spermiogenesis (low LDH-X and diminished CK-M ratios). Because of this heterogeneity, LDH-X ratios will be a poor predictor of sperm maturity. The data support the hypotheses: (1) LDH and CK concentrations were higher in oligospermic vs. normospermic men (P < 0.001). (2) The LDH and CK concentrations were related (r = 0.65, P < 0.001, N = 145), and there were inverse correlations between CK, LDH, LDH-X, or CK-M ratios vs. sperm concentrations (P < 0.001 in all four). (3) The CK-M and LDH-X ratios were different between the oligospermic and normospermic groups (P < 0.001), although the means of the LDH-X ratios were narrower (LDH-X:1:1.3; CK-M:1:1.9). (4) Dividing the 145 samples by the cut-off value of mean minus 1 SD of the CK-M and LDH-X ratios (11% and 32%, respectively) demonstrated that the CK-M ratios discriminated better than LDH-X ratios between the samples with mature and immature sperm. These data on the biochemical markers of early and late spermatogenesis support the studies in which CK better reflected sperm quality than LDH or LDH-X (Orlando et al., 1994: Int J Androl 17:13-18) and the > 10% sperm CK-M ratio predicted with a rate of 30.4% per cycle in the occurrence of pregnancies in a blinded study of 84 IVF couples (Huszar et al., 1992: Fertil Steril 57:882-888).

Biomarkers↗
PubMed2000

Expression of lactate dehydrogenases A and B during chicken spermatogenesis: characterization of testis specific transcripts.

The substrates required for glycolysis change markedly at successive stages of spermatogenesis suggesting a considerable plasticity in the expression of glycolytic enzymes. Lactate dehydrogenase (LDH) isoenzymes, LDH-A and LDH-B, are expressed in premeiotic, meiotic cells, and early spermatids, both in avian and mammalian spermatogenesis. Highly polyadenylated forms, particularly of LDH-A, were detected in chicken testis. While mammals and columbid birds express the testis specific LDH-C gene in meiotic and postmeiotic cells, several LDH-B testis specific transcripts were detected in the corresponding cells during chicken spermatogenesis. These testis specific transcripts and the mRNA of mammalian LDH-C show several properties in common, such as temporal correlation of expression, mRNA stability, and repression of premature translation. These observations suggest that the testis specific transcripts could perform during chicken spermatogenesis the functions of the LDH-C mRNA in mammalian testis.

5' Untranslated Regions↗
PubMed1986

Impaired spermatogenesis in testes at risk of torsion.

The oligospermia observed after unilateral torsion of the spermatic cord could reflect immunological damage to the opposite testis. An alternative explanation, that there may be a pre-existing defect in spermatogenesis, was tested in 20 post-pubertal males with acute torsion. In a prospective study the contralateral testis was biopsied at operation and the histological appearances were related to subsequent testicular function as assessed by seminal analysis 3 months later. Thirteen patients had biopsy evidence of partial maturation arrest in spermatogenesis which was either mild (6), moderate (4) or severe (3), and ten of these were oligospermic (less than 20 X 10(6)/ml). By contrast all seven patients with normal histology had a sperm concentration greater than 25 X 10(6)/ml. Histological grading of spermatogenesis by the Johnsen technique gave a higher score in patients with a normal biopsy (median 9.01, semi-quartile range 8.96-9.21) than in those with abnormal histology (median 8.28, semi-quartile range 7.98-8.45, P less than 0.001) and correlated with the log of the sperm concentration 3 months later (r = 0.79, P less than 0.001). There was minimal anti-sperm and no anti-testis antibody formation following torsion. Serum FSH levels were raised in 6 of 10 oligospermic patients, while all those with a normal sperm count had FSH concentrations within the normal range. Thus many patients who develop testicular torsion have an underlying defect in spermatogenesis, which correlates closely with poor postoperative exocrine function.

Adult↗
PubMed2005

Flow cytometric characterization of viable meiotic and postmeiotic cells by Hoechst 33342 in mouse spermatogenesis.

BACKGROUND: Spermatogenesis in adult is a complex stepwise process leading to terminally differentiated spermatozoa. The cellular heterogeneity of testis renders complex the studies on molecular aspects of this differentiation process. Analysis of the regulation of adult spermatogenesis would undoubtedly benefit from the development of techniques to characterize each germinal differentiation step. METHODS: Hoechst 33342 staining of mouse testicular cells allows characterization of an enriched population in germinal stem cell and spermatogonia, called side population. In this study, we examined the definition of the various germinal populations stained by Hoechst 33342, notably meiotic and postmeiotic cells. RESULTS: Preleptotene spermatocytes, spermatocyte I, spermatocyte II, and round and elongated spermatids were discriminated by Hoechst 33342 staining. In addition, we associated differentiation of spermatocyte I through leptotene to diplotene with changes in Hoechst 33342 red fluorescence pattern. CONCLUSIONS: Hoechst 33342 staining of viable germinal cells constitutes a valuable tool to study normal and impaired mouse adult spermatogenesis or to isolate viable cells from various differentiation stages for studies of molecular mechanisms regulating spermatogenesis.

Animals↗
PubMedDate not supplied

Male hormonal contraception: suppression of spermatogenesis by injectable testosterone undecanoate alone or with levonorgestrel implants in chinese men.

Monthly injections of testosterone undecanoate (TU) act as a male contraceptive by reversibly suppressing spermatogenesis to azoospermia or severe oligoazoospermia in 95% of Chinese men. In 5% of Chinese men, however, monthly TU administered alone fails to suppress spermatogenesis into contraceptive ranges, or sperm "rebound," leading to occurrences of pregnancy during treatment. Since combinations of progestins and androgens are associated with greater degrees of sperm suppression in white men, we hypothesized that the combination of TU and the progestin levonorgestrel (LNG) would result in improved spermatogenic suppression in Chinese men. Sixty-two healthy Chinese men were randomly assigned to one of the following 3 regimens: group I (n = 21) received 4 LNG rods (75 mg each), which were followed 4 weeks later by 500 mg of TU by intra-muscular (IM) injection every 8 weeks for 24 weeks; group II (n = 20) received 4 LNG implants, which were followed 4 weeks later by 1000 mg of TU by IM injection every 8 weeks for 24 weeks; and group III (n = 21) received TU 1000 mg by IM injection every 8 weeks for 24 weeks. Sperm counts, serum testosterone (T), luteinizing hormone, follicle-stimulating hormone, and LNG were measured every 2 weeks before, during, and after treatment. During treatment, group II demonstrated a trend toward a greater attainment of azoospermia than groups I and III (90% vs 62% [group I] vs 67% [group III]; P =.09). Attainments of either azoospermia or oligozoospermia (sperm density, <3 x 10(6)/mL) were 95%, 100%, and 86% for groups I, II, and III, respectively (P >.05 for comparisons between groups). Spermatogenesis in all subjects returned to the normal range after the implants were removed. No serious adverse events and no significant changes in serum chemistry occurred during the study. These results demonstrate that the combination of IM injections of high-dose TU every 2 months and LNG implants is associated with marked suppression of spermatogenesis in Chinese men. The combination of high-dose TU every 2 months and LNG implants is a promising candidate for future large-scale efficacy studies of hormonal male contraception in Chinese men.

Absorbable Implants↗
PubMed1975

Gene activation during spermatogenesis.

Cell differentiation during spermatogenesis in the rat has been analyzed in terms of the formation of specific "marker" enzymes. Hyaluronidase and other acrosomal enzymes are formed in spermatids according to a highly predictable time schedule which may be termed a "molecular biological clock". The acrosomal enzymes beta-galactosidase and N-acetyl-beta-glucosaminidase exist as isoenzyme forms distinct from enzymes with similar substrate specificities in the lysosomes of precursor cells. Differentiation of spermatids thus involves the loss of gene expression for lysosomal enzymes and the activation of genes for acrosomal isoenzymes. Spermatogenesis is characterized by the sequential loss of expression of many genes, as evidenced by the loss of beta-glucuronidase in the differentiation of spermatogonia to spermatocytes, and the loss of uridine diphosphatase activity in the differentiation of spermatocytes to spermatids. The apparent absence of ornithine decarboxylase activity from spermatids suggests a dependence of these cells upon Sertoli cells for the provision of putrescine and/or spermidine. Such biochemical cooperativity among germinal cells may be necessary as the genes of spermatids are repressed and late spermatids become metabolically inactive. Spermatogenesis is also characterized by changes in the cellular content and rates of synthesis and phosphorylation of specific acidic chromatin proteins. It is hypothesized that these proteins may participate in the activation or repression of genes during spermatogenesis.

Acetylglucosaminidase↗
PubMed2005

Germ cell death in the testis and its relation to spermatogenesis in the wax moth, Galleria mellonella (Lepidoptera: Pyralidae), effects of facultative diapause.

The dichotomous spermatogenesis of many Lepidopterans results in the production of two types of sperm: eupyrene sperm possessing a cell nucleus which participates in fertilisation, and apyrene ones, which lose their nuclei during development and whose function remains a mystery. The goal of our study was to analyse spermatogenesis at the end of the larval development of the wax moth, Galleria mellonella, at an optimal temperature of 30 degrees C as well as to describe how they are affected by diapause brought on by a reduction of temperature to 18 degrees C. Spermatogenesis in non-diapausing insects did not differ significantly from that described in other species of Lepidoptera, and any differences found were compared against available literature. Based on the results presented, it may be unequivocally stated that changes in spermatogenesis occur in diapause caused by a suboptimal temperature of 18 degrees C. The main effect of diapause observed in the testes is the degeneration of germ cells, immediately following their differentiation from bipotential spermatocytes. Eupyrene cells seem to reach a more advanced stage of development. Due to the absence of secondary eupyrene spermatocytes in the testis of diapausing insects, it may be surmised that the meiotic divisions, which lead to the formation of secondary spermatocytes and eventually spermatids, do not occur, or are somehow altered. Lastly, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling (TUNEL) analyses we performed show that the degenerative changes of eupyrene cells are apoptotic in character.

Adaptation, Physiological↗
PubMed2004

Stages in spermatogenesis of two species of caecilians, Ichthyophis tricolor and Uraeotyphlus cf. narayani (Amphibia: Gymnophiona): Light and electron microscopic study.

The sequential changes during spermatogenesis in the testis of two species of caecilians, Ichthyophis tricolor (Ichthyophiidae) and Uraeotyphlus cf. narayani (Uraeotyphliidae), of Western Ghats of Kerala, India, were traced using both histological techniques and transmission electron microscopy. The cell nests were assigned to stages in spermatogenesis based on the classification of van Oordt (1956, Thesis, Utrecht University). To the best of our knowledge, this is the first identification and ultrastructural description of stages in spermatogenesis in caecilians. The article illustrates not only the stages, but also the cell divisions, mitotic and meiotic, as specified. The observations indicate that, although caecilians have undergone considerable modifications in morphology and anatomy, including reproductive anatomy, in the context of a subterranean and concealed life, they appear to have conserved the typical amphibian pattern of spermatogenesis for the events of development of spermatids.

Amphibians↗
PubMed2001

Stage-dependent and alternative splicing of sGnRH messengers in rainbow trout testis during spermatogenesis.

The gonadotropin releasing hormone (GnRH) has long been considered as a neuropeptide involved in the control of the reproductive cycle. However, the presence of GnRH and its receptors in various tissues, including ovary and testis, suggests a role as autocrine/paracrine factor. In the present study, we report the expression of the sGnRH-1 and sGnRH-2 genes encoding salmon GnRH in rainbow trout testis throughout testicular development and spermatogenesis. We demonstrate that both sGnRH mRNA are expressed prior of sexual differentiation. In adult, northern blot analysis indicates that sGnRH-2 transcripts are expressed in the testis at higher levels than sGnRH-1 messengers. Moreover, we observed that the expression of sGnRH-2, and not sGnRH-1, messengers was stage-dependent. sGnRH-2 mRNA expression decreases at the onset and progressively rebounds at the end of spermatogenesis. In addition, we demonstrate that a complex stage-dependent and differential splicing of the sGnRH-2 messengers occurs throughout spermatogenesis. We isolated five transcripts corresponding to sGnRH-2 messengers. Two of them may encode a novel and shortened GnRH-associated peptide containing 18 residues instead of 46. Our data provide new insight in the putative role of GnRH and GAP peptides as autocrine/paracrine factors of spermatogenesis.

Alternative Splicing↗
PubMed2002

Effects of the aromatase inhibitor fadrozole on plasma sex steroid secretion, spermatogenesis and epididymis morphology in the lizard, Podarcis sicula.

Recently, increasing importance has been attached to the role of estrogens and their receptors in male reproduction, since they have been found to be abundant in the male reproductive tract. In the lizard, Podarcis sicula, a seasonal breeder, estrogens seem to be involved in the regulation of testicular activity. Particularly, it has been hypothesized that the block of spermatogenesis and the complete regression of the epididymis and other secondary sexual characters (SSCs) in autumn might be due to high estrogen levels. To investigate the role of estrogens in the reproductive process of male lizards, we utilized Fadrozole ((AI) [4-(5,6,7,8-tetrahydroimidazole [1,5-a] pyridin-5-yl)-benzonitrile monohydrochloride] (CGS 16949A)), a nonsteroidal inhibitor of aromatase, the enzyme involved in the aromatization of androgens to estrogens, evaluating its effects on plasma sex-hormone release, spermatogenesis and epididymis morphology. For this purpose, adult male lizards, captured during the autumnal recrudescence, were intraperitoneally injected with 0.5 microg and 5 microg/g/body weight of AI for 15 and 30 days. In the animals treated with the higher AI dose, estrogen levels decreased if compared to the control groups, whereas androgen levels increased. Furthermore, histologic sections of testes and epididymes showed that the 30-day treatment with AI-induced spermatogenesis resumption with release of sperms into the large lumen of the seminiferous tubules, and the epididymes appeared more developed with moderately secreting columnar canal cells. Therefore, it is proposed that failure of spermatogenesis in autumn might be due to high estrogen levels.

Animals↗
PubMed2003

Gamma-ray exposure accelerates spermatogenesis of medaka fish, Oryzias latipes.

To examine the spermatogenesis (and spermiogenesis) cell population kinetics after gamma-irradiation, the frequency and fate of BrdU-labeled pre-meiotic spermatogenic cells (spermatogonia and pre-leptotene spermatocytes) and spermatogonial stem cells (SSCs) of the medaka fish (Oryzias latipes) were examined immunohistochemically and by BrdU-labeling. After 4.75 Gy of gamma-irradiation, a statistically significant decrease in the frequency of BrdU-labeled cells was detected in the SSCs, but not in pre-meiotic spermatogenic cells. The time necessary for differentiation of surviving pre-meiotic spermatogenic cells without delay of germ cell development was shortened. More than 90% of surviving pre-meiotic spermatogenic cells differentiated into haploid cells within 5 days after irradiation, followed by a temporal spermatozoa exhaust in the testis. Next, spermatogenesis began in the surviving SSCs. However, the outcome was abnormal spermatozoa, indicating that accelerated maturation process led to morphological abnormalities. Moreover, 35% of the morphologically normal spermatozoa were dead at day 6. Based on these results, we suggest a reset system; after irradiation most surviving spermatogenic cells, except for the SSCs, are prematurely eliminated from the testis by spermatogenesis (and spermiogenesis) acceleration, and subsequent spermatogenesis begins with the surviving SSCs, a possible safeguard against male germ cell mutagenesis.

Animals↗
PubMed2003

Apoptosis during spermatogenesis in the spotted ray Torpedo marmorata.

This article is a cytological and molecular investigation on the occurrence of apoptosis during spermatogenesis in Torpedo, a cartilaginous fish characterised by a typical cystic testis. Using DNA fragmentation and Bak gene expression, it demonstrated that germ cells undergo apoptosis only at the stages of spermatocyte and spermatid, and degeneration also involves Sertoli but not Leydig cells. In immature cysts, this cellular process probably occurs when the ratio of germ cells to the only Sertoli cell (SC) forming the spermatoblast changes. Apoptosis also takes place in mature cysts after sperm release to eliminate most of the SCs. Few of them, however, become cytoplasts and probably continue secreting androgens so as to control the final events of spermatogenesis, i.e., passage of spermatozoa through the ductus deferentes. Finally, the present investigation demonstrated that, in Torpedo testis, Bak mRNA is expressed during spermatogenesis, thus suggesting that the mitochondrial pathway might be active. This observation in one of the oldest vertebrate classes indicates that, in all vertebrates, the apoptotic process during spermatogenesis is conserved, contributing to testicular homeostasis.

Animals↗
PubMed2006

Tyrosine protein kinases and spermatogenesis: truncation matters.

Protein phosphorylation on serine/threonine or tyrosine residues represents a significant regulatory mechanism in signal transduction during spermatogenesis, oogenesis, and fertilization. There are several families of tyrosine protein kinases operating during spermatogenesis: the Src family of tyrosine protein kinases; the Fujinami poultry sarcoma/feline sarcoma (Fps/Fes) and Fes-related protein (Fer) subfamily of non-receptor proteins; and c-kit, the transmembrane tyrosine kinase receptor that belongs to the family of the PDGF receptor. A remarkable characteristic is the coexistence of full-length and truncated tyrosine kinases in testis. Most of the truncated forms are present during spermiogenesis. Examples include the truncated forms of Src tyrosine kinase hematopoietic cell kinase (Hck), FerT, and tr-kit. A feature of FerT and tr-kit is the kinase domain that ensures the functional properties of the truncated protein. FerT, a regulator of actin assembly/disassembly mediated by cortactin phosphorylation, is present in the acroplaxome, a cytoskeletal plate containing an F-actin network and linking the acrosome to the spermatid nuclear envelope. This finding suggests that Fer kinase represents one of the tyrosine protein kinases that may contribute to spermatid head shaping. The c-kit ligand, stem cell factor (SCF), which induces c-kit dimerization and autophosphorylation, exists as both membrane-associated and soluble. Although tyrosine protein kinases are prominent in spermatogenesis, a remarkable observation is the paucity of phenotypic alterations in spermatogenic cells in male mice targeted with Fer kinase-inactivating mutation. It is possible that the redundant functions of the tyrosine protein kinase pool present during spermatogenesis may explain the limited phenotypes of single mutant mice. The production of compound and viable mutant mice, lacking the expression of two or more tyrosine kinases, may shed light on this intriguing issue.

Animals↗
PubMed2003

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.

Adolescent↗