Biomedical subjects

L D Russell

Publications and source records attributed to L D Russell.

At least 55 records · Page 3Linked to original sources

PubMed1994

The urethral glands of male mice in relation to depletion of secretory granules upon mating.

The present study describes the effects of mating on urethral gland acinar cells in male mice. Histological and morphometric analysis demonstrated that there was a depletion of secretory granules in the urethral glands during mating. However, no change occurred in the rough endoplasmic reticulum containing tubular elements. The results indicate that the urethral glands are functional during mating. The timing of their granule depletion suggests that urethral gland secretions may contribute to the formation of semen or the copulation plug.

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PubMed1993

Ultrastructure and morphometry of the urethral glands in normal, castrated, and testosterone-treated castrated male mice.

Recent studies of the urethral glands in the male mouse and rat have suggested that they are testosterone-dependent glands that may be potential sites for secretory immunity in the male genital tract. In the present study we describe the ultrastructural features of these glands in normal mice and provide quantitative data on the sizes of the acinar cells and their organelles in sham-, oil-, and testosterone-treated castrated mice. Acinar cells in urethral glands from normal mice contain numerous secretory granules, prominent Golgi complexes, elongated mitochondria, and an abundance of rough endoplasmic reticulum (RER) with large and dilated cisternae, all of which are features characteristic of secretory cells. In some acinar cells the cisternae of the RER were filled with closely packed, unbranched, straight, tubular structures that were oriented parallel to one another, that radiated from aggregates of dense material, or that were randomly arranged. In other acinar cells the cisternae of the RER showed a network of branching and anastomosing vesicular-like structures whose limiting membranes were occasionally seen in continuity with the membranes of the RER. Secretory acini showed large, unbranched tubules in the acinar lumen. When cut at right angles the large tubules exhibited a distinct fuzzy outer coat with fine projections radiating outwards. The ultrastructure of the acinar cells and the presence of tubules in the lumen suggests that they are engaged in secretion of a tubular protein. Morphometric analysis of acinar cells in the urethral glands showed that the mean volumes of nuclei, cytoplasm, secretory granules, vacuoles, and mitochondria were significantly reduced in castrated mice in comparison to either normal or testosterone-treated castrated mice. This confirms earlier observations that the urethral glands are targets of testosterone.

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PubMed1993

Sertoli cell cycle: a re-examination of the structural changes during the cycle of the seminiferous epithelium of the rat.

Seminiferous tubules in mammals are composed of cell associations that show a cyclic pattern of renewal and development. The cyclic nature of germ cell development suggests that the cells supporting the spermatogenic process, the Sertoli cells, might also differ structurally during the spermatogenic cycle in terms of the quantity of their constituents. In the present study, cyclic differences in volumes, and surface areas were determined using a sampling technique at the electron microscope level that proportionally samples the Sertoli cell within the seminiferous tubule. Among the many parameters studied, only the surface area of the cell, the volume of lipid, and the volume and surface area of the rough endoplasm reticulum were shown by statistical analysis to vary cyclically. Regarding rough endoplasm reticulum, the volume and surface area of this organelle peaked at mid-cycle and its low was recorded near the end of the cycle, exhibiting an approximate 15-fold difference between extremes. The rough endoplasm reticulum parameters generally correlated with known patterns of protein secretion within the tubule and with the secretion of specific proteins as well as the factors important in controlling protein secretion. Many Sertoli cell structural parameters suggested to be influenced cyclically in the rat in other studies could not be confirmed by the present study. Methodological differences in the present study and past studies are discussed as potential sources of error for these discrepancies.

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PubMed1993

Regulated expression of testis angiotensin-converting enzyme during spermatogenesis in mice.

A unique isozyme of angiotensin-converting enzyme (ACE) is produced in large amounts by developing germ cells and is referred to as testis ACE. This protein results from the transcriptional recognition of a sperm-specific promoter during spermatogenesis. The expression within germ cells of testis ACE mRNA was studied using in situ hybridization, ribonuclease (RNase) protection, and Northern analysis. In parallel, testis ACE protein expression was measured through use of Western blot analysis and immunohistochemistry. Although testis ACE protein is first detected in step 10 spermatids, testis ACE mRNA is first detected in a developmentally younger cell population, late pachytene spermatocytes. Thus, testis ACE mRNA is translationally arrested for a period of several days until late in spermiogenesis.

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PubMed1993

Surface and surface-to-volume relationships of the Sertoli cell during the cycle of the seminiferous epithelium in the rat.

The surface relationships of the Sertoli cell and the surface relationships of the Sertoli cell in comparison to the changing volumes of developing germ cells were studied using morphometric techniques at periods representing nine groupings of the fourteen defined periods in the cycle of the seminiferous epithelium of the adult rat. No cyclic variation in the total Sertoli plasma membrane surface area was noted. Cyclic variations were noted in the area of the Sertoli cell surface that faces the basal compartment germ cells, but not the basal lamina. No cyclic variations were noted in the amount of contact of the Sertoli cells with each other at the level of the Sertoli cell barrier. However, when areas in the adluminal compartment were studied, significantly less Sertoli-Sertoli contact was seen in stages V through VII than in other stages with the exception of stages II-IV. Surface contact of germ cells with Sertoli cells increased progressively as germ cells entered the intermediate compartment and progressed to late spermatids. However, a calculation of the surface-to-volume ratio showed that surface increases of the Sertoli cell in relation to the volume of germ cells were greatest in elongating spermatids past step 12 of spermiogenesis. The area in which Sertoli ectoplasmic specializations faced germ cells was determined throughout spermatogenesis, and these data demonstrated that the first appearance of ectoplasmic specialization was at the mid-pachytene phase. They also showed that stage VIII was a period when ectoplasmic specialization loss from the cell surface was evident. Less Sertoli ectoplasmic specialization face step 8 and step 19 spermatids than comparable germ cell types at other stages. In addition to Sertoli cell surface area changes during the cycle, volumes of individual germ cell types were determined for the first time. The data presented allow an objective understanding of the complex structure and relationships of the Sertoli cell and provide a basis for understanding functional changes and interpreting biochemical data.

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PubMed1993

Sentinels of Leydig cell structural and functional changes in golden hamsters in early testicular regression and recrudescence.

The seasonally breeding hamster model was used to assess changes associated with Leydig cell activity and inactivity. Specifically, parameters of Leydig cell structure and function were studied to determine the early changes seen in seasonally breeding golden hamsters in photoperiod-induced gonadal regression and photoperiod-induced gonadal recrudescence. Time intervals used to characterize early regression and recrudescence were selected with the objective of determining the most sensitive parameters characterizing functional transitional states. In early regression, plasma levels of follicle-stimulating hormone (FSH) but not luteinizing hormone (LH) or testosterone were reduced significantly. Regressive structural changes included decreases in volume of the interstitium, total number of Leydig cells, blood vessels, and the seminiferous tubules and tubular lumen. A decrease in volume, but not numbers of Leydig cells, was accompanied by decreases in volume of Leydig cell tubular smooth endoplasmic reticulum (t-ER), Golgi complex, and the peroxisomes and decreases in surface area of the inner mitochondrial membrane and t-ER, suggesting that early Leydig cell changes are restricted primarily to organelles associated with steroid biosynthesis. In early recrudescence, at a time when there was an increase in the number of germ cells in the basal compartment, blood levels of LH, FSH and testosterone were all increased. There were increases in testicular weight, volume, seminiferous tubular lumen, blood vessel and interstitial volumes. Leydig cells increased in size as a result of increases in nuclear, nucleolar and cytoplasmic volumes, while Leydig cell numbers did not increase. At the subcellular level there were increases in the surface areas of the cell, mitochondrial membranes and cisternal endoplasmic reticulum (sparsely populated with ribosomes). Unlike the changes seen in early degeneration when steroid synthetic organelles were initially affected, the changes in early recrudescence indicate that Leydig cells must first rebuild their synthetic machinery (nucleus, nucleolus and rough endoplasmic reticulum) that, at a later time, will reconstitute the cell's steroidogenic machinery. Correlation of hormonal parameters with structural parameters did indicate a relationship between hormonal parameters and steroid secreting organelles. Correlations were strongest with testosterone but, surprisingly, plasma FSH levels correlated more strongly with many structural parameters of the Leydig cell than did the levels of LH. Since FSH receptors are not present on Leydig cells, these data add to the growing data suggesting a role for factors originating from the seminiferous tubule in modulation of Leydig cell function.

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PubMed1993

Recombinant human follicle-stimulating hormone is capable of exerting a biological effect in the adult hypophysectomized rat by reducing the numbers of degenerating germ cells.

There is considerable controversy as to whether FSH can, under normal circumstances, exert an effect to promote spermatogenesis in the adult rat. Recombinant human FSH (rhFSH) was used to answer a more limited question relating to whether FSH is capable of exerting a biological effect in promoting adult spermatogenesis. Can a pure preparation of FSH prevent the regressive changes seen after hypophysectomy (Hx) in a short term experiment? To answer this question, five groups of adult rats were used as follows: pituitary-intact animals, 3-day hypophysectomized (Hx), 3-day Hx given 3 mg testosterone propionate (T)/day for 7 days, 3-day Hx given 22 IU rhFSH for 7 days, and 3-day Hx given saline vehicle for 7 days. Testis weight, seminiferous tubule diameter, analysis of four degenerating germ cell types, the relative amount of lipid, and the levels of FSH receptors showed that FSH could, in a significant manner, prevent the regressive changes accompanying Hx. FSH was not as effective as T in doing so, because the FSH values were always intermediate between T-maintained animals and those after long term Hx. The Leydig cell was eliminated as a possible source of FSH-stimulated T promotion of spermatogenesis, given that morphometry and tissue T assays indicated that no additional production of T was elicited by rhFSH. The assay system used to enumerate degenerating germ cells proved a very sensitive indicator of the ability of hormones to maintain cell viability in short term experiments. The data not only show that FSH can exert a biological effect, but that this effect is qualitatively similar to that seen after the administration of T in terms of the maintenance of viability of specific germ cell types. A hypothesis is presented whereby FSH and T, although the former acting by a second messenger system and the latter by binding to nuclear receptors, can stimulate the genome to exert similar qualitative effects promoting the viability of germ cells.

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PubMed1992

Structural response of the hamster Sertoli cell to hypophysectomy: a correlative morphometric and endocrine study.

Reproductively active hamsters were hypophysectomized and examined 6 or 20 days later in a combined morphometric and endocrine study of the Sertoli cell to determine 1) the morphological and endocrine effects of hypophysectomy of both short- and long-term duration, 2) if regression of Sertoli cells after hypophysectomy in a seasonal breeder resembles regression due to seasonal changes, and 3) if effects of hypophysectomy in a seasonal breeder are equivalent to the effects of hypophysectomy in a nonseasonal breeder. Six days after hypophysectomy, at a period when germ cell degeneration is first noted, there was a significant decrease in testis weight, interstitial space, tubule diameter and length, volume of seminiferous tubule, and tubular lumen. There were no significant changes in Sertoli cell nuclear and cytoplasmic volume although cell surface area was decreased significantly. Most organelles exhibited no significant change in volume or surface area except for secondary lysosomes which expectedly increased in volume as the result of phagocytosis of germinal cells. Thus at an early time period when functional changes in germ cells and Leydig cells are clearly evident (Russell et al. [1992] Endocrinology), the Sertoli cell shows minimal changes. Twenty days after hypophysectomy, the cell, nuclear and cytoplasmic volumes and surface area of the Sertoli cells, and volumes and surface areas of nearly all organelles were significantly decreased from values measured in normal and in short-term hypophysectomized hamsters. The exceptions were the total volumes of lipid which increased significantly and lysosomes which were similar to normal but significantly lower than short-term hypophysectomized animals. The long-term hypophysectomized hamster Sertoli cell, like that of the short-day hamster (Sinha Hikim et al. [1989b] Endocrinology, 125:1829-1843) is structurally regressed as a whole rather than exhibiting selective decreases in cellular and subcellular components. The size of the Sertoli cell in pituitary-intact, long- and short-term hypophysectomized animals showed positive and significant correlations with the volumes and surface areas of all its cytoplasmic organelles except the volume of lipid which showed a negative, significant correlation. Comparisons of long-term hypophysectomized hamsters (in long-day light exposure) and short-day exposed animals (Sinha Hikim et al. [1989b] (Endocrinology, 125:1829-1843) suggested that hypophysectomy, in general, resulted in similar, but slightly more severe regressive changes in the testis and germ cell population than those seen during seasonal regression.(ABSTRACT TRUNCATED AT 400 WORDS)

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PubMed1992

Quantitation of Sertoli cell-germ cell desmosome gap junctions in relation to meiotic divisions in the male rat.

Desmosome-gap (D-G) junctions were quantified in relation to germ cell meiosis in the male, specifically to test the hypothesis that the loss of these junctions is related to successful passage of cells through diplotene phase of Meiosis I and the two cytokineses that follow. Such a hypothesis has been proposed as the cause for the resumption of meiosis that occurs prior to ovulation in the female. D-G junctions were quantified in pachytene spermatocytes (stage XII), diplotene spermatocytes (stage XII), secondary spermatocytes (stage XIV) and step 1 spermatids (stage I). These were referred to as the cells of interest as compared with spermatocytes (zygotene spermatocytes, zygotene spermatocytes, pachytene spermatocytes, pachytene spermatocytes) in the same stages, respectively, that served as controls termed control cells. Since gap junctions are not easily recognized in the average sectioned profile of a desmosome-gap junction, only the desmosomal component was quantified. The data were expressed as both numbers and length of junctions per tubule, per cell profile and per unit lineal membrane length to overcome errors inherent in the methodologies utilized. There was no indication that numbers of junctions changed specifically in the cells of interest after passage through diplotene suggesting that these junctions do not have a comparable role in meiotic continuance in the male as proposed for the female. Interestingly, the control cells always showed greater numbers and length of junctions than the cells of interest suggesting that junction may relate more to the period of initiation of meiosis than to its continuance.

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PubMed1992

Reproductive toxicity of theobromine and cocoa extract in male rats.

The toxicities of theobromine and cocoa extract on the reproductive tract of male rats were compared in the present study. A cocoa powder extract containing 117 mg theobromine/g extract was prepared using 85% boiling methanol. Sprague-Dawley rats were weighed and dosed daily for 31 days with vehicle, 250 mg/kg theobromine, 2.14 g/kg cocoa extract (117 mg theobromine/g extract), or 0.43 g/kg cocoa extract by oral gavage. The animals were sacrificed on day 32. One testis and epididymis were removed and weighed. The epididymis was saved for the determination of epididymal sperm reserves. The remaining testis was fixed by whole body glutaraldehyde perfusion and processed for morphologic examination. A decrease in body weight gain and epididymal weights were observed in theobromine and high-dose cocoa-extract-treated groups. Theobromine and high-dose cocoa extract caused vacuolation within the Sertoli cell, abnormally shaped spermatids, and failed release of late spermatids in treated animals. Most of the vacuolations were found in the earlier and middle stage seminiferous tubules (stages I to VIII). However, the frequency of some parameters of testis alterations were significantly lower in the high-dose cocoa-extract-treated group compared to the theobromine-treated group. These data demonstrate the ability of a cocoa extract containing theobromine to alter testis structure in a similar pattern but with reduced intensity compared to that observed after oral exposure to pure theobromine.

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PubMed1992

Urethral glands of the male mouse contain secretory component and immunoglobulin A plasma cells and are targets of testosterone.

The occurrence and possible functions of mucosal immunity in the male urogenital tract have not been extensively investigated. In this study we used immunolabeling to localize secretory component (SC) and immunoglobulin (Ig) A in the urogenital tract of the male mouse. SC was located in the ventral prostate, while SC and IgA plasma cells were both detected in the urethral glands in the pelvic and bulbous portions of the urethra. SC and IgA were not observed elsewhere in the urogenital tract. We also examined the ventral prostate and urethral glands of sham-castrated, oil-treated castrated, and testosterone-treated castrated mice. There was a striking reduction in the size of the ventral prostate and urethral glands in oil-treated castrates compared to the other two groups, based on gross and histological morphology. Morphometric analysis showed that the cell and nuclear sizes of the urethral gland acinar cells were reduced after castration and restored to normal size by testosterone treatment. Androgen receptors (AR) were localized in the nuclei of urethral gland cells by immunocytochemistry using anti-AR antibodies. Labeling of SC and IgA plasma cells was similar in the urethral glands and ventral prostates of sham- and testosterone-treated castrates, but was reduced or absent at these sites in oil-treated castrates. These studies show that the ventral prostate and urethral glands may be sites for secretory immunity in the male murine urogenital tract, and that the urethral glands are targets for testosterone.

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PubMed1992

Structural manifestations of the rat Sertoli cell to hypophysectomy: a correlative morphometric and endocrine study.

Although the Sertoli cell is a key cell mediating the actions of FSH- and LH-stimulated testosterone (T) in the testis, there is little information to indicate how this cell responds structurally to hormonal insufficiency. The present study used morphometric techniques to study the structural manifestations of the Sertoli cell in adult rats hypophysectomized for 6 and 28 days. Six days posthypophysectomy, a period when germ cell degeneration is first evident, tubular diameter and length, testis weights, volume of the interstitium, and volume of most parameters that comprise the interstitium (except blood vessels) showed significant regressive features. However, virtually no parameter relating to the volume and surface area of the Sertoli cell or its subcellular components was significantly reduced compared with that in the normal animal. Thus, at a time when germ cell degeneration is seen in the testis, the Sertoli cell showed no significant structural response to the changing endocrine status of the animal. In contrast, 28 days after hypophysectomy, virtually all parameters relating to the Sertoli cell and its organelles were significantly decreased compared with those in normal animals. Plasma and tissue testosterone, PRL, and FSH showed a very significant decrease 6 days after hypophysectomy compared with intact animals, but at 28 days there was no further significant decrease in the levels of these hormones. There was no correlation of most organelle volumes and surface areas with endocrine parameters. The size of the Sertoli cell showed positive and significant correlations with the volumes and surface areas of all of its cytoplasmic organelles, except the lipid volume. Short term hypophysectomy resulted in no significant change in either the concentration (femtomoles per mg protein) or the content (femtomoles per testis) of FSH receptors, nor was there a significant change in the number of FSH receptors per cell. However, 28 days after hypophysectomy only the content, not the concentration, of FSH receptors decreased significantly along with a decrease in the number of FSH receptors per cell. Although the marked degenerative changes that are seen in the testis 6 days after hypophysectomy parallel endocrine decline, the Sertoli cell responded slowly from a structural standpoint compared with the Leydig cell. After long term hypophysectomy, significant morphometric changes were observed in all of its structural parameters.

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PubMed1992

Structural changes in rat Leydig cells posthypophysectomy: a morphometric and endocrine study.

Short and long term responses of the rat Leydig cell were studied posthypophysectomy, at times when germ cell degeneration was first prominent (6 days) and after long term regression of the testis (28 days). In the short term, virtually all structural parameters relating to the volume and surface area of the Leydig cell and its subcellular organelles were significantly lowered compared with those in control animals. Exceptions were the volumes of the nucleolus, heterochromatin, and lysosomes and the surface areas of the nucleus. Structural decreases were generally on the order of 2- to 5-fold in the 6-day period. A statistical analysis of the percent decreases in the short term was performed to determine whether any particular structural features were more sensitive to hypophysectomy than any others. In most instances, no particular organelles were decreased compared to others. However, lipid, although not commonly seen in rat Leydig cells, showed significantly greater percent decreases compared with several other organelles, indicating that the small amount of lipid present is rapidly lost (used) in the short term. After long term hypophysectomy, all structural parameters of the Leydig cell were significantly lowered compared with those in pituitary-intact animals. Only a few parameters (mitochondrial volume, cell surface area, and the surface areas of inner and outer mitochondrial membranes and smooth endoplasmic reticulum) showed more significant decreases in the long term compared with the short term hypophysectomized animals. Most organelle volumes and surface areas correlated positively and significantly with serum and tissue testosterone levels; the exceptions were the volumes of the nucleolus, heterochromatin, lipid, and lysosomes. Compared with the pituitary-intact animal, the content of LH receptors expressed per testis and per Leydig cell was significantly lower in both hypophysectomized groups; however, the number of receptors per given area of individual Leydig cell plasma membrane remained unchanged. Overall, data show that the Leydig cell manifests marked structural changes during early spermatogenic dysfunction.

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PubMed1991

Linkage of manchette microtubules to the nuclear envelope and observations of the role of the manchette in nuclear shaping during spermiogenesis in rodents.

Structural features of the mouse and rat manchette and the role of the manchette in shaping the spermatid nucleus were investigated. Rod-like elements about 10 nm in diameter and 40-70 nm in length were seen linking the innermost microtubules of the manchette and the outer leaflet of the nuclear envelope in step 8 through step 11 rat and mouse spermatids that either had been routinely fixed for electron microscopy or had been isolated and detergent extracted. Rod-like linkers were also seen joining the nuclear ring to the plasma membrane and nuclear envelope. These linkers may ensure that under normal conditions the manchette remains in a defined position relative to these membranous components. A variety of compounds (taxol, cytoxan, and 5-fluorouracil) were found to perturb the manchette and to affect nuclear shaping. In addition, sys and azh mutant mice were used to determine the consequences of defective manchette formation. These genetic conditions and chemical treatments either produced manchettes that were not in their normal position (azh, sys, and taxol) and/or caused the manchette to appear abnormal (azh, sys, cytoxan, 5-fluorouracil, and taxol), and all resulted in a deformation of the step 9-11 spermatid nucleus. In all instances where the manchette was present, either in normal or ectopic locations, the sectioned nuclear envelope was parallel to the long axis of the microtubules of the manchette. In general, areas of the nuclear envelope where the manchette was not present, or where it was expected to be present but was not, were rounded (normal animals, sys, cytoxan). In addition, there are indications using certain compounds (cytoxan and 5-fluorouracil) as well as in the azh and sys mouse that the manchette may exert pressure to deform the nucleus. It is suggested that the rod-like linkages of the manchette ensure that the nuclear envelope remains at a constant distance from the manchette microtubules and that this is a major factor acting to impart nuclear shape changes on a region of the head caudal to the acrosome during the early elongation phase of spermiogenesis. The manchette microtubules, which are also known to be linked together, may act as a scaffold to deform this part of the nucleus from its spherical shape, perhaps in concert with forces initiated by other structural elements. Evidence from sys animals indicates that structural elements, such as the acrosomal complex over the anterior head (acrosome-actin-nuclear envelope), may affect nuclear shaping over the acrosome-covered portion of the spermatid head.(ABSTRACT TRUNCATED AT 400 WORDS)

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PubMed1991

Clonal development of interconnected germ cells in the rat and its relationship to the segmental and subsegmental organization of spermatogenesis.

Segments and subsegments are the smallest unit of synchrony thus far described within longitudinal sections of seminiferous tubules. It is known that cells in a clone joined by intercellular bridges are at the same phase of development and are also thought to be units of synchrony. This study was designed to determine if it is possible that the synchrony seen in cells joined by intercellular bridges is the same as that cataloged along the long axis of the seminiferous tubule. In the present study, the maximum number of rat spermatids joined by intercellular bridges (a clone) was obtained. It was hypothesized that if the clone size were larger than the smallest known units of synchrony (segments or subsegments) in the long axis of the seminiferous tubule, then intercellular bridges would most likely govern the synchronous development of segments or subsegments (or finer subdivisions thereof). If the clone size is smaller than the number of cells present in a segment or subsegment, then other factors must govern synchrony in the longitudinal aspect of the tubule. In the determination of spermatid clone size, rat testes were injected with cytochalasin D which opens intercellular bridges of a spermatid clone to produce large symplasts. The number of nuclei in the symplasts was determined from serially sectioned tissue, by drawing nuclei with a camera-lucida, and by counting nuclei. After extensive examination of tubules, the number of spermatids found in the suspected five largest clones observed was determined to be 650, 607, 338, 240, and 177.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1991

Localization of boar sperm proacrosin during spermatogenesis and during sperm maturation in the epididymis.

The localization of proacrosin was determined by using colloidal gold labeling and electron microscopy of boar germ cells during spermiogenesis to post-ejaculation. Proacrosin was first localized in round spermatids during the Golgi phase of spermiogenesis; it was associated with the electron-dense granule, or acrosomal granule that was conspicuous within the acrosome. It remained within the acrosomal granule during the cap and acrosome phases of spermiogenesis. At these stages, there was no apparent association of the proacrosin molecule with the acrosomal membranes. During the maturation phase of spermiogenesis, proacrosin was seen to become dispersed into all regions of the acrosome except the equatorial segment. When sperm from different segments of the epididymis and ejaculated sperm were examined, localization was observed throughout the acrosome except for the equatorial segment. Here proacrosin appeared to be localized on both the inner and outer acrosomal membranes as well as with the acrosomal matrix, although further studies are required to verify the membrane localization. No labeling was seen on the plasma membrane. These data suggest that the synthesis and movement of proacrosin to sites in the acrosome are controlled by an as yet unknown process. The absence of proacrosin on the plasma membrane of mature ejaculated sperm makes it unlikely that this enzyme plays a role in sperm-zona adhesion prior to capacitation.

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PubMed1991

Short-term morphological response of the rat testis to administration of five chemotherapeutic agents.

As cancer survival rates improve, there is increasing concern about the adverse effects of chemotherapeutic agents on male fertility. Five chemotherapeutic agents (amethopterin, AP or methotrexate; doxorubicin, DX; cytoxan or cyclophosphamide, CP; cisplatinum, CDDP; and 5-fluorouracil, 5-FU) which belong to three different categories of chemotherapeutic agents (antimetabolite, antibiotic, alkylating agent, alkylating agent, antimetabolite, respectively) were given systemically to adult rats to determine the short-term morphological patterns of response in the testis, and the testes were examined by light microscopy. Morphological patterns of response were found to be highly characteristic for each agent, and some shared morphological responses were evident. All except one chemotherapeutic agent (5-FU) caused spermatogonial damage. Among the defects seen were probable degenerating meiotic spermatocytes (CDDP), presence of micronuclei (DX), "arrested" spermatid development (5-FU), and abnormally shaped step 15 spermatids (5-FU). Damage that could be due to the effect of an agent on the Sertoli cell was failure of sperm release (5-FU, CDDP, DX, and AP), increase in the Sertoli cell lipid (5-FU), and malorientation of step 8 spermatids (5-FU, DX). The varied patterns of damage observed are a possible explanation of why the reproductive recovery potential in cancer patients undergoing chemotherapy is variable and drug-specific.

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PubMed1991

Testis structure in the sys (symplastic spermatids) mouse.

Testes of mice with the recessive insertional mutation termed symplastic spermatids (sys) were assessed for structural and developmental abnormalities. Homozygous (sys/sys) males are infertile due to an abnormality in spermatogenesis leading to azoospermia. The major interruption to spermatogenesis occurs when the intercellular bridges that connect round spermatids open prematurely resulting in the formation of symplasts. Symplasts contain as many as 285 nuclei. Development of spermatids within symplasts is arrested just before, or just after, elongation of the spermatid nuclei begins. Symplasts degenerate and appear to be phagocytized by Sertoli cells and by intratubular macrophages. In addition, degeneration of young round spermatids and also spermatocytes occasionally is observed. Spermatocyte degeneration is substantial in some tubules and leaves them depleted of cells other than basal compartment cells. Sertoli cell abnormalities are prominent and include intracellular vacuolation, absence of apical processes surrounding round spermatids, degeneration, and occasional sloughing. Although reduplication and infolding of the basal lamina is also seen, this does not appear as a common phenomenon. The sys phenotype is first manifest in animals between 19 days and 22 days of age. Considerable variability is seen in testis histology of prepubertal animals; some display degenerating pachytene spermatocytes and virtually no Sertoli cell vacuoles, while others display vacuoles without apparent elevated numbers of degenerating spermatocytes. Although this study has not revealed the primary cell type(s) affected by the insertional inactivation event, it is possible that the abnormalities in the Sertoli cells are responsible for germ cell degeneration as it is generally recognized that deficits in the Sertoli cell can result in major germ cell abnormalities but not vice versa.

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