| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Regular Article |
a Institute of Reproductive Medicine of the University, D-48129 Münster, Germany
b Department of Reproductive Biology, German Primate Centre, D-37077 Göttingen, Germany
ABSTRACT
Spermatogenesis is characterized by the succession in time and space of specific germ cell associations (stages). There can be a single stage (e.g., rodents and some macaques) or more than one stage (e.g., chimpanzee and human) per tubular cross section. We analyzed the organization of the seminiferous epithelium and quantified testicular germ cell production and apoptosis in a New World primate, the common marmoset (Callithrix jacchus). Tubule cross sections contained more than one stage, and the human six-stage system could be applied to marmoset spermatogenesis. Stereological (optical disector) analysis (n = 5) revealed high spermatogenic efficiency during meiosis and no loss of spermatids during spermiogenesis. The conversion of type A to type B spermatogonia was several-fold higher than that reported for other primates. Highest apoptotic rates were found for S-phase cells (20%) and 4C cells (15%) by flow cytometric analysis (n = 6 animals); histological analysis confirmed spermatogonial apoptosis. Haploid germ cell apoptosis was <2%. Marmoset spermatogenesis is very efficient and involves substantial spermatogonial proliferation. The prime determinants of germ cell production in primates appear to be proliferation and survival of spermatogonia rather than the efficiency of meiotic divisions. Based on the organizational similarities, common marmosets could provide a new animal model for experimental studies of human spermatogenesis.
apoptosis, gametogenesis, meiosis, spermatogenesis, testes
INTRODUCTION
Spermatogenesis encompasses mitotic divisions of spermatogonia, meiotic divisions of spermatocytes yielding haploid germ cells, and the morphological differentiation and maturation of round spermatids into elongated spermatids. The complexity of the spermatogenic process mandates tight and well-balanced control mechanisms evidenced by the precise duration of spermatogenesis and the presence of defined germ cell associations. These germ cell associations are referred to as stages of spermatogenesis, and they vary in number and duration in a species-specific manner. The stage classification system is based upon the morphological development of spermatids [1, 2].
Among mammals, two major differences exist in the topographical arrangement of the spermatogenic stages. In rodents, only one specific spermatogenic stage is seen in a round cross section through a seminiferous tubule. An orderly succession of the consecutive stages along the tubules was discovered from the analysis of longitudinal tubular sections (stage I followed by stage II, stage III, etc.) and is referred to as the wave of spermatogenesis [3]. In other species, however, such as chimpanzees (Pan troglodytes) [4] and humans [5, 6], several spermatogenic stages can usually be recognized within the same tubular cross section. In the cynomolgus monkey (Macaca fascicularis) [7] and in the olive baboon (Papio anubis), an intermediate picture has been described. For the baboon, 60% of tubule sections showed the presence of one stage and 40% showed the presence of two or three stages [8]. It has been proposed for the human testis that the presence of several stages results from a helical organization of spermatogenesis [9], but this view has been challenged, suggesting rather that the arrangement of stages is random [10]. This irregular pattern of spermatogenesis [6] along with the absence of germ cell generations has been associated with deficient germ cell production [11]. In humans, a large proportion of germ cells apparently degenerate during spermatogoniogenesis and approximately 50% of spermatocytes are lost during meiosis [12]. However, a more recent study [13] indicated that human spermatogenesis could be more efficient than previously thought. Quantitative studies of spermatogenesis in macaques (cynomolgus monkeys) revealed little or no germ cell loss during meiosis and spermiogenesis [14].
The biological significance of the irregular pattern of spermatogenesis with regard to germ cell production remains unclear, and an easily accessible animal model is lacking. The common marmoset (Callithrix jacchus) is a New World nonhuman primate that has been used in reproductive biology and toxicology investigations for many years [15–17]. In the present investigation, germ cell and Sertoli cell numbers and testicular apoptosis were quantified for the first time in this species. Holt and Moore [18] described nine stages of spermatogenesis, and subsequent work suggested that the distribution of spermatogenic stages in the common marmoset resembles that of humans, with more than one stage per tubule cross section [19]. Therefore, we also examined whether the six-stage system, commonly used for stage-related analysis of human spermatogenesis [5], could also be applied to the marmoset germinal epithelium.
MATERIALS AND METHODS
Tissues and Processing
Testes from 11 intact adult normal male common marmosets were used. The testicular weight was 0.3–0.6 g. One testis each from five animals was immersion fixed in Bouin's solution and stored in 70% ethanol at 4°C until preparation for stereological analysis. Testes from six animals were used for analysis of apoptotic cells. Testicular tissue was fixed in Carnoy's solution for histological analysis of cells for TUNEL, and parts were freshly prepared for flow cytometric analysis of cell populations and quantitative anaysis using TUNEL.
Stereological Analysis
Testes were sliced into four to six equal pieces at right angles to the long axis. Following dehydration, all pieces were embedded in resin (hydroxethyl-methacrylate) according to the manufacturer's protocol (Technovit 7100; Heraeus Kulzer GmbH, Wehrheim, Germany). Three slices per testis were selected using the systematic uniform random sampling approach [20]. Sections were cut at 25 µm and stained with periodic acid and hematoxylin. Oxidation was carried out in 1% periodic acid for 30 min and in Schiff's reagent for 45 min. Counterstaining with Mayer's hematoxylin lasted for 35 min. To enhance staining intensity, sections were placed in Scott's tap water (Sigma Diagnostics, St. Louis, MO) for 5 min prior to mounting in Vitro-Clud (Fa. Langenbrinck, Emmendingen, Germany).
The number of germ cells per testis was determined using the optical disector method as previously described [14, 20]. Nuclear number was assumed to equal cell number. Cell counts were not performed according to spermatogenic stages. Sections were analyzed using an 100x oil immersion lens with a numerical aperture of 1.3 on an axioscopic microscope (Zeiss, Oberkochen, Germany) equipped with an ocular net grid and a device to measure section thickness. Microscopic fields for counting were selected using a systematic uniform random sampling scheme [21]. The upper surface of the section was brought into focus, and the first 3 µm were ignored to avoid possible surface imperfections. The next 10–18 µm (depth) were then examined, focusing through the cell, and the nuclei were counted as they came into focus according to the disector principle [22]. Sixty frames corresponding to 6400 µm2 were evaluated per animal.
The numerical density (NV) of each cell type was calculated by dividing the number of cells counted by the volume of all disectors (NV = no. cells counted/area of frame x no. frames x depth). The number of cells per testis was calculated based upon Nv (NV x testis weight). A near 1:1 ratio was assumed between testis weight and volume [23]. The germ cells were grouped into A and B spermatogonia, preleptotene, leptotene, and zygotene (PL/L/Z) spermatocytes, pachytene spermatocytes (PS), round spermatids (RS), and elongated spermatids (ES), irrespective of the spermatogenic stage. Sertoli cell numbers were determined as described for the germ cells.
Spermatogenic Stages
Sections (3–4 µm) were prepared to analyze the germ cell associations. For spermatogonia, the nomenclature provided by Holt and Moore [18] for the marmoset testis was used. The seminiferous epithelium was categorized into different stages on the basis of the six cellular associations described for the human testis [24]. One hundred seminiferous tubules were analyzed per testis to determine the frequency of the six stages. If one tubule cross section contained more than one spermatogenic stage, each stage was counted as a separate tubule. This approach enabled the determination of the incidence of each of the six stages. The percentage of stage frequencies and the cumulative stage frequencies were calculated. Based on these values, germ cell numbers per testis were adjusted to the presence in all stages for calculation of the conversion ratios for the various germ cell types and the germ cell:Sertoli cell ratios.
Flow Cytometry
Testicular cells were stained with propidium iodide (PI) as previously described [25]. The PI-stained cells were analyzed using a flow cytometer (EPICS XL; Coulter, Krefeld, Germany) equipped with 15-mW argon ion laser at an excitation wavelength of 488 nm. The fluorescence signals of the PI-stained germ cells were collected with a 620 band pass filter (605–635 nm). For determination of the proportion of TUNEL cells, a protocol reported previously was used [25]. About 1–2 x 106 ethanol-fixed testicular cells/ml were washed in PBS, treated with 0.5% pepsin solution, and resuspended in terminal deoxynucleotidyl transferase (TdT) buffer (Promega, Madison, WI; Serva, Heidelberg, Germany) and biotinylated deoxyuridine triphosphate (Boehringer-Mannheim GmbH, Mannheim, Germany). Following incubation at 37°C for 30 min, cells were resuspended in buffer containing fluoresceinated avidin (Boehringer-Mannheim) and then incubated for another 30 min in the dark. Control cells were processed as described but without TdT. The intensity of the green fluorescence of avidin-fluorescein isothiocyanate (FITC) and the red fluorescence of PI-stained cells was measured on a flow cytometer (EPICS XL; Coulter) equipped with a 15-mW argon ion laser at an excitation wave length of 488 mm. The fluorescence signals of FITC were collected with a 525 band pass filter (505–545 nm) and those of PI were collected with a 620 band pass filter (605–635 nm). The setting of markers in the TUNEL histograms for the cutoff between background signal and positive staining was determined from the control samples and was applied to analyis of treated samples to quantify TUNEL-positive cells.
Histological Analysis of Apoptotic Cells
TUNEL analysis was performed on testicular tissue that was fixed in Carnoy's fluid, dehydrated, embedded in paraffin according to routine procedures, and sectioned at 5 µm. The protocol for TUNEL has been described [25, 26]. Sections (3 µm) were deparaffinized, rehydrated, washed for 10 min in running water, and rinsed in TdT buffer. The sections were incubated with reaction mixture containing TdT buffer, 0.5 nM of biotin-16-deoxyuridine triphosphate (Boehringer-Mannheim) and 5 units of TdT (Promega; Serva) in a moist chamber for 1 h at 37°C. The reaction was terminated by rinsing the slides thoroughly in Tris buffer. Extravidin-peroxidase complex and diaminobenzidine (Sigma, Diesenhofen, Germany) were used to visualize the biotinylation, and hematoxylin was used as a counterstain when appropriate. Control slides were processed in an identical manner except for the omission of TdT.
RESULTS
Organization of the Seminiferous Epithelium
Testis weights ranged from 0.3 to 0.6 g, and spermatogenesis was complete in all animals. The cellular association pattern described for the human testis could be applied to describe marmoset spermatogenesis. The nine stages described by Holt and Moore [18] were redefined as follow: stage I remains stage I, stages II and III are combined to make up stage II, stage IV becomes stage III, stages V and VI are combined to make up stage IV, stages VII and VIII are combined to make up stage V, and stage IX becomes stage VI. The germ cell composition of the six stages is provided in Table 1, and histological pictures are provided in Figure 1, C–H. Cellular organization of the germinal epithelium was characterized by the presence of more than one spermatogenic stage per tubular cross section (Fig. 1A). Few tubules contained a single stage (mainly stage III). Tubules with many stages were seen occasionally, including repetition of the same stage and germ cell associations (Fig. 1B). Although the different stages could easily be recognized, the boundaries between the different stages could not be delineated precisely in all instances. Stage frequencies (mean ± SEM) were 27.6% ± 1.5% for stage I, 7.8% ± 1.2% for stage II, 41.0% ± 2.0% for stage III, 13.8% ± 1.4% for stage IV, 19.2% ± 1.6% for stage V, and 4.2% ± 0.7% for stage VI.
|
|
Testicular Cell Numbers and Germ Cell Conversion Ratios
The testes contained 192.2–434.5 x 106 cells. Germ cell numbers (mean ± SEM; x106 cells/testis) were 3.5 ± 0.5 for type A spermatogonia, 8.3 ± 1.7 for type B spermatogonia, 27.2 ± 3.7 for PL, 48.0 ± 6.1 for PS, 102 ± 19 for RS, and 115 ± 20 for ES (Table 2). A mean (± SEM) of 18.3 ± 1.9 x 106 Sertoli cells were present per testis. On average, 1 Sertoli cell was associated with 16.5 germ cells (all cell types) and 11.7 haploid germ cells (Table 2). To determine germ cell conversion ratios, the expected number of daughter cells resulting from division of the parent cell was compared with the values actually obtained. To account for the life span of the parent and daughter cells, the cell numbers were adjusted based on stage frequencies by the formula described previously [27]. The ratio of B:A spermatogonia was close to 8 and the PL/L/Z:B ratio was around 2, suggesting four spermatogonial divisions prior to entry into meiosis (Table 3). RS:PS ratio was >3, indicating only slight loss of germ cells during meiosis. No germ cells were found to be lost during spermatid maturation (ratio of 1.1).
|
|
By histological analysis, dividing cells in the basal part of the seminiferous epithelium were considered to be spermatogonia and were observed in stages I, III, IV (rarely), and VI (Table 1). A1 spermatogonia were not abundant and had ovoid nuclei, frequently with two nucleoli (Fig. 1E). A2 spermatogonia were generally larger than A1 spermatogonia, and their nuclei contained one or two nucleoli (Fig. 1F). The nuclear morphology of A1 and A2 spermatogonia was variable but could not be related to specific spermatogenic stages. B spermatogonia showed variable nuclear morphology and size, comprising large round nuclei with a prominent nucleolus (Fig. 1D) and sometimes heterochromatin near or at the nuclear periphery or smaller nuclei with several crustlike chromatin structures (Fig. 1C). However, as seen for A spermatogonia, the occurrence of morphologically distinct B spermatogonia did not always correlate with a particular spermatogenic stage.
Apoptosis
Based on the DNA content distribution, flow cytometric analysis of testicular germ cells of the marmoset showed five main peaks: HC (ES; H = hypostainability of the compacted DNA during spermiogenesis), 1C (RS), 2C (mainly spermatogonia and somatic cells), S-ph (cells in the S-phase of the cell cycle), and 4C (tetraploid cells comprising mainly of primary spermatocytes and G2-spermatogonia cells). Testes contained (mean ± SEM) 18% ± 1% HC cells, 55% ± 1.5% 1C cells, 14% ± 1 2% C cells, 3% ± 0.4% S-ph cells, and 10% ± 0.7% 4C cells (Fig. 2). The percentage of TUNEL cells in each category is depicted in Figure 2. No specific signals could be detected in HC cells, and the percentage of apoptotic 1C cells was low (1.5% ± 0.5%). In contrast, 15–20% of dividing cells, on average, were apoptotic, with highest values among S-ph cells. Histologically, TUNEL cells could be identified mainly as spermatogonia and some early spermatocytes (Fig. 1, I and J). Overall, the majority of apoptotic cells were considered spermatogonia based upon the relative position in the seminiferous epithelium and upon nuclear size/shape. The occurrence of these apoptotic cells was spread across all stages of spermatogenesis.
|
DISCUSSION
In this investigation, we aimed to characterize for the first time spermatogenesis through quantitative data on testicular germ cell production and apoptosis in a New World nonhuman primate species. The unbiased optical disector method was used for quantification of testicular germ cells, and flow cytometry was used to determine quantitatively the incidence of apoptosis. The marmoset testis produces high numbers of type B spermatogonia. Analysis of the conversion of type A into type B yielded a value of 7.7. This ratio exceeds that reported for the cynomolgus monkey by 5-fold [27] and that for normal humans by 20-fold [13]. Because the conversion ratio of type B spermatogonia into early spermatocytes was 2.5, we might assume that marmoset spermatogenesis encompasses four spermatogonial divisions. Histological analysis supports this view, and dividing cells in the basal part of the seminiferous epithelium that were considered spermatogonia were observed in stages I, III, IV, and VI. Kinetic studies, however, are required to ultimately clarify the number of mitoses in the marmoset testis.
On average, 6% of 2C cells, 15% of 4C cells, and 20% of S-ph cells were apoptotic in the marmoset testis, as revealed by flow cytometric analysis. Histological analysis confirmed that these cells were mainly spermatogonia. Generally, around 30% of cells in the marmoset testis belonged to the 2C, S-ph, and 4C cell populations, which contain, aside from somatic cells and spermatocytes, the spermatogonia. This value is slightly higher than that reported for macaques (approximately 25%) [28, 29] but is markedly higher than that reported for rodents (approximately 15%) [25, 28]. We are not aware of quantitative flow cytometrical data on testicular apoptosis in other primate species. In the mouse model, however, spermatogonium/spermatocyte apoptosis is much less frequent, amounting to 2% for 2C cells, 3% for 4C cells, and 6% for S-ph cells [25]. Thus, marmoset spermatogenesis appears to be characterized by a particularly high spermatogonial/spermatocyte turnover. Whether this situation is specific for marmosets or whether it holds true for other primate species remains to be seen.
Holt and Moore [18] reported that the marmoset spermatogonial system resembles that described for other primates. This system comprises reserve stem cells (A1 spermatogonia), renewing stem cells (A2 spermatogonia), and B spermatogonia [1, 30, 31]. Our data also suggest the presence of mainly two types of A spermatogonia. Other researchers have also reported that morphologically different B spermatogonia are present in the marmoset testis [18]. However, because the appearance of morphologically different spermatogonia did not follow a stage-related pattern and because we lack kinetic data for marmoset spermatogonia, it was not possible to reliably determine the respective spermatogonial numbers and their renewal patterns for the various spermatogenic stages. Clearly, further studies including 3H-thymidine or 5-bromodeoxyuridine incorporation and analysis of whole mount tubules are required to unravel the marmoset spermatogonial (renewal) system. The presence of several stage per cross section further complicates the analysis, but the reduction from nine to six stages might become useful in that regard.
Because the optical disector approach has previously also been utilized for testicular cell quantification in other primates, including normal humans [13, 14, 27], direct comparisons of the spermatogenic efficacy in marmosets, macaques, and humans can be made. In the marmoset, only a few germ cells were lost during spermatid maturation, and similar data have been collected for macaques and humans. Our flow cytometric data also confirm that the rate of spermatid apoptosis is very low (1.5%). In terms of the production of haploid germ cells from PS during meiotic divisions, the three species were similar, with conversion ratios of 3.0–3.5. These data also indicate that germ cell loss during primate meiosis is clearly lower than previously thought. Stereological analysis of semithin sections of human testis tissue suggested a 50% cell loss during the meiotic divisions [12, 32]. The reason for the discrepant findings in humans is unclear at present. However, our recent data and those reported earlier suggest that primate spermatogenesis is quite efficient and that the meiotic germ cell loss is not related to the arrangement of spermatogenic stages. The major difference among macaques, marmosets, and humans resides in the spermatogonial system of divisions as discussed above. Hence, germ cell production in the primate testis appears to be primarily determined by spermatogonial proliferation and survival rather than meiotic divisions. Once a primate spermatogonium has entered meiosis, the likelihood for development of this germ cell into an ES is at least 75%.
We attempted to apply the human spermatogenic classification system (six stages) introduced by Clermont [24] to the marmoset testis because others researchers [19] have suggested that the organization of the seminiferous epithelium in marmosets is comparable to that of humans, i.e., several spermatogenic stages per tubular cross section. The presence of several stages per cross section was very obvious, and it remains unclear why this finding had not been noted in the initial morphological description of marmoset spermatogenesis [18]. The human six-stage system [5] is based on the presence of typical cellular associations and morphological changes of spermatid nuclei in the seminiferous tubules rather than on the development of the acrosome, and the six stages could easily and conveniently be assigned to marmoset spermatogenesis. The nine spermatogenic stages described by Holt and Moore [18] correspond to the six stages as follows: stage I remains stage I, stages II and III are combined into stage II, stage IV becomes stage III, stages V and VI are combined into stage IV, stages VII and VIII are combined into stage V, and stage IX becomes stage VI. These observations further corroborate the similarity between human and marmoset seminiferous epithelial architecture [19]. It had been noticed previously [18] that in the marmoset testis, spermatogenic stages could be described better on the basis of cellular associations rather than acrosome development. The staging scheme for human spermatogenesis could also be successfully applied to a proportion of tubules in the cynomolgus monkey [7].
Human spermatogenic stage arrangement has been described as irregular [6], helical [9], or random [33], and it is unclear whether a complete spematogenic wave exists in the human testis. We did not set out to determine whether a partial or complete spermatogenic wave exists in the marmoset testis. However, because marmosets diverged from the human line more than 35 x 106 yr ago, it is tempting to speculate that the pattern of human spermatogenesis either has evolved on at least two occasions or has been (partially) lost in other primate species. In rhesus macaque (Macaca mulatta) and stumptailed macaque (M. arctoides) testes, one stage per tubular cross section is predominant [1, 34], and olive baboons are intermediate [8]. Regardless of which of these two evolutionary scenarios is correct, the organizational principle of the human and chimpanzee [35] seminiferous epithelium in all likelhood is neither particular nor specific to these species but might be more common among primates than previously thought.
Despite the organizational similarities of the spermatogenic stages, the frequency of these stages differs substantially between human and marmoset. Stage III was clearly the most frequent stage (41%) in the marmoset, and when only one stage was present in a tubule, it was usually stage III. The high frequency of this stage suggests that it may have the longest duration [1]. In contrast, for humans the average frequency (based on four specimens) for stage III was only 6.4% (range, 2.5–11.5%) [24]. In the chimpanzee, the frequency of stage III was also highest (31%) [24, 35]. Other substantial although smaller differences were present for stages IV and V, whereas the frequency of stages I and VI was nearly identical.
In summary, marmoset spermatogenesis shares organizational similarities with that of humans but is highly efficient. Thus, the irregular/helical/random arrangement of spermatogenic stages is not necessarily disadvantageous with regard to quantitative germ cell yields. Among the primates studied so far, the marmoset shows the highest spermatogonia conversion of type A to type B. Hence, the marmoset should be a useful model for germ cell transplantation studies [36]. Marmoset spermatogonia frequently undergo apoptosis, indicating a high spermatogonial turnover in this species. In contrast to previous suggestions, we propose that the prime determinant of germ cell yields in the primate testis is the proliferation and survival of spermatogonia rather than meiotic divisions.
NOTE ADDED IN PROOF
A recent publication based upon analysis of spermatogenesis from semithin sections using the 9-stage classification system also concluded that marmosets could provide a suitable model for the study of human spermatogenesis.Millar MR, Sharpe RM, Weinbauer GF, Fraser HM, Saunders PT. Marmoset spermatogenesis: organizational similarities to the human. Int J Androl 2000; 23:266–277.
ACKNOWLEDGMENTS
We are grateful to Dr. E. Nieschlag, Institute of Reproductive Medicine, for his continued support and critical comments. The technical assistance of R. Sandhowe-Klaverkamp, M. Heuermann, and G. Stelke is gratefully acknowledged.
FOOTNOTES
First decision: 23 February 2000.
1 Supported by the Deutsche Forschungsgemeinschaft (G.F.W., H.A., A.E., J.K.H.) and by the Bundesministerium fuer Bildung und Forschung (M.H.B.). Preliminary data from this investigation were presented at the 32nd Annual Meeting of the Society for the Study of Reproduction, Pullman, WA, 1999. 
2 Correspondence: G.F. Weinbauer, Covance Laboratories GmbH, Kesselfeld 29, D-48163, Münster, Germany. FAX: 49 251 784697; gerhard.weinbauer{at}covance.com
3 Current address: Molecular Reproduction Research Laboratory, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada.
4 Current address: Department of Biomedical Sciences, University of Bradford, Bradford, West Yorkshire BD7 1DP, United Kingdom.
Accepted: August 15, 2000.
Received: January 19, 2000.
REFERENCES
This article has been cited by other articles:
|
|
 |
|
  R.T. Mitchell, G. Cowan, K.D. Morris, R.A. Anderson, H.M. Fraser, K.J. Mckenzie, W.H.B. Wallace, C.J.H. Kelnar, P.T.K. Saunders, and R.M. Sharpe Germ cell differentiation in the marmoset (Callithrix jacchus) during fetal and neonatal life closely parallels that in the human Hum. Reprod., August 11, 2008; (2008) den295v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Godmann, V. Auger, V. Ferraroni-Aguiar, A. D. Sauro, C. Sette, R. Behr, and S. Kimmins Dynamic Regulation of Histone H3 Methylation at Lysine 4 in Mammalian Spermatogenesis Biol Reprod, November 1, 2007; 77(5): 754 - 764. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. H. Volle, K. Mouzat, R. Duggavathi, B. Siddeek, P. Dechelotte, B. Sion, G. Veyssiere, M. Benahmed, and J.-M. A. Lobaccaro Multiple Roles of the Nuclear Receptors for Oxysterols Liver X Receptor to Maintain Male Fertility Mol. Endocrinol., May 1, 2007; 21(5): 1014 - 1027. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. H. Volle, R. Duggavathi, B. C. Magnier, S. M. Houten, C. L. Cummins, J.-M. A. Lobaccaro, G. Verhoeven, K. Schoonjans, and J. Auwerx The small heterodimer partner is a gonadal gatekeeper of sexual maturation in male mice Genes & Dev., February 1, 2007; 21(3): 303 - 315. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. K Chandolia, C. M. Luetjens, J. Wistuba, C.-H. Yeung, E. Nieschlag, and M. Simoni Changes in endocrine profile and reproductive organs during puberty in the male marmoset monkey (Callithrix jacchus). Reproduction, August 1, 2006; 132(2): 355 - 363. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Leal and L. R. Franca The Seminiferous Epithelium Cycle Length in the Black Tufted-Ear Marmoset (Callithrix penicillata) Is Similar to Humans Biol Reprod, April 1, 2006; 74(4): 616 - 624. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Segatelli, L. R. Franca, P. F. F. Pinheiro, C. C. D. Alemida, M. Martinez, and F. E. Martinez Spermatogenic Cycle Length and Spermatogenic Efficiency in the Gerbil (Meriones unguiculatus) J Androl, November 1, 2004; 25(6): 872 - 880. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wistuba, A. Schrod, B. Greve, J. K. Hodges, H. Aslam, G. F. Weinbauer, and C. M. Luetjens Organization of Seminiferous Epithelium in Primates: Relationship to Spermatogenic Efficiency, Phylogeny, and Mating System Biol Reprod, August 1, 2003; 69(2): 582 - 591. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Zuhlke and G. Weinbauer The Common Marmoset (Callithrix jacchus) as a Model in Toxicology Toxicol Pathol, January 1, 2003; 31(1_suppl): 123 - 127. [Abstract] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
