Search PubMed⌕ Search

Biomedical subjects

L D Russell

Publications and source records attributed to L D Russell.

At least 73 records · Page 4Linked to original sources

Structural characteristics of immature rat Sertoli cells in vivo and in vitro.

The structural properties of pelleted prepubertal Sertoli cells (pre-culture pelleted cells) from 19-day-old rats and of similar cells cultured for 7 days were compared with Sertoli cells from the intact animal (testis tissue from 19- and 26-day-old rats, the in vivo groups). Sertoli cells from freshly isolated pellets and those cultured for 7 days were similar in cell and nuclear volumes to their in vivo counterparts. Cell volumes, organelle volumes, and organelle volume densities of newly isolated Sertoli cells were similar to those of sectioned cells taken from the 19-day-old in vivo group, indicating that the procedure for isolation does not grossly alter Sertoli cells. Mean height of cells cultured for 7 days was significantly lower than that of cells from intact animals at 19 and 26 days of age. In vivo, Sertoli cells of 26-day-old animals displayed increased organelle volumes and organelle surface areas compared with those from 19-day-old animals; volume densities and surface densities remained relatively constant, indicating that in vivo, organelle growth is in proportion to growth of the cell. Most organelle volume and surface densities were not significantly different when 19-day-old in vivo cells and pre-culture pelleted cells were compared. Many organelle volume and surface density values were significantly less in cells grown in culture for 7 days as compared to freshly isolated pelleted cells. After 7 days of culture, most Sertoli cell organelles were significantly less in both volume density and surface density, as compared to the in vivo cell groups (19 or 26 day). This indicates that in vitro the organelles do not develop in proportion to the growth of the cell. After 7 days in culture, the absolute volumes and surface areas of the organelles remained generally unchanged as compared to cells from 19-day-old animals. The data show that Sertoli cells grow in volume in vitro like their in vivo counterparts; however, their subcellular features, although well maintained, do not develop in proportion to the cell. This suggests that short-term cultures are a more ideal system in which to study biochemical responses. Also, cultured prepubertal Sertoli cells are most appropriately used to study prepubertal Sertoli cell function. This is the first study to quantify developmental changes in Sertoli cell structure in vivo as well as to compare them with cellular changes occurring in vitro.

Aging↗

Reinitiation of spermatogenesis by exogenous gonadotropins in a seasonal breeder, the woodchuck (Marmota monax), during gonadal inactivity.

The present study was undertaken (1) to document structural and functional changes in the testes of seasonally breeding woodchuck during active and inactive states of spermatogenesis and (2) to evaluate the ability of exogenous gonadotropins to reinitiate spermatogenesis outside the breeding season. During seasonal gonadal inactivity, there were significant (P less than 0.05) reductions in volumes of several testicular features (testis, seminiferous tubules, tubular lumen, interstitial tissue, individual Leydig cells, Leydig cell nuclei, and Leydig cell cytoplasm) as compared with gonadally active animals. The diameter of the seminiferous tubules was decreased by 26%, and Leydig cell numbers also declined in the regressed testes. These changes were accompanied by a decline in testosterone (T) levels in both plasma and testis, and reduction in epithelial height of accessory reproductive organs. A hormonal regimen was developed that would reinitiate spermatogenesis in captive, sexually quiescent woodchucks. A combination of PMSG and hCG markedly stimulated testicular growth and function and restored spermatogenesis qualitatively. Quantitatively normal spermatogenesis was restored in 2 of 6 treated males. Morphometric analyses revealed substantial increases in seminiferous tubular diameter and in the volume of seminiferous tubules, tubular lumen, total Leydig cells, and individual Leydig cells in the hormone-treated animals. These increased values corresponded to 99, 75, 68, 51, and 200%, respectively, of the values measured in naturally active woodchucks. Leydig cell numbers, however, remained unchanged and approximated only 31% of the number found in naturally active testes. Hormonal stimulation also resulted in a significant rise in serum T as well as in the total content of testicular T, and a marked increase in epithelial height in various accessory reproductive glands. The most effective hormonal protocol for stimulating spermatogenesis was treatment with 12.5 IU of PMSG twice a week for 4 weeks followed by 12.5 IU of PMSG + 25 IU of hCG twice a week for 4 weeks.

Animals↗

Further observations of stage-specific effects seen after short-term hypophysectomy in the rat.

Although hypophysectomy has been a popular tool to study the effects of hormone deprivation as well as concomitant or subsequent hormone supplementation, there is relatively little morphological information available on the structural manifestation of pituitary removal on the testis. In the report, changes, in addition to those previously reported after short-term (6 days) hypophysectomy in the rat (Russell and Clermont, 1977), are described. Membrane-bound vacuoles (primarily) appeared within the basal region of the Sertoli cell at approximately the level of Sertoli-Sertoli junctions. In stages VIII through XI elongating spermatids were abnormal and manifested manchette indentation of the nucleus, a variety of other abnormal head shapes, acrosomal breaks and enlargement of the subacrosomal space. These defects were interpreted as the effect of declining hormonal levels in stage VII on spermatids that had survived the stage VII hormone sensitivity known to occur with severe hormone depletion. Abnormalities in the flagellum involving the mitochondrial sheath and fibrous sheath were detected. Preleptotene spermatocytes degenerated and could be identified in the process of doing so near the base of the seminiferous epithelium. The contact of preleptotene spermatocytes with the basal lamina was also significantly reduced. The results show that both Sertoli cell and germ cell abnormalities were present although germ cell abnormalities could be a secondary consequence of lack of appropriate stimulation of the Sertoli cell. Degeneration of basal compartment germ cells shows that germ cells other than those located in the adluminal compartment are vulnerable to hormonal withdrawal. The question of how hormone effects are mediated in the testis at midcycle to produce these effects is discussed.

Animals↗

Presence and localization of a 30-kDa basic fibroblast growth factor-like protein in rodent testes.

We have used a recently characterized rabbit antiserum against basic fibroblast growth factor (bFGF), which recognizes various forms of bFGF, to examine the presence and localization of bFGF in the testes of adult rats and mice and the 5-day-old rat. In Western blots of testicular homogenates of adult rats and mice and immature rats, immunoreactive single bands at approximately 30 kDa were detected. Immunocytochemistry revealed specific staining restricted to the tubular compartment. In 5-day-old rat testes, prespermatogonia were immunoreactive. The cytoplasm of pachytene spermatocytes was heavily stained in the adult testes of both species. Staining of these cells became evident around stage IV/V, was prominent in stage VII through IX and declined about stage XII/XIII (rat) or X-XI (mouse). Staining was seen in type A spermatogonia and in elongating spermatids in their cytoplasmatic lobes and along their flagellae. Sertoli cells were unstained. We propose that the pluripotential growth factor bFGF could be involved in the regulation of germ cell proliferation and differentiation in the adult and immature testis.

Aging↗

A comparative study in twelve mammalian species of volume densities, volumes, and numerical densities of selected testis components, emphasizing those related to the Sertoli cell.

Morphometric studies were performed on 12 mammalian species (degu, dog, guinea pig, hamster, human, monkey, mouse, opossum, rabbit, rat, stallion, and woodchuck) to determine volume density percentage (Vv%), volume (V), and numerical density (Nv) of seminiferous tubule components, especially those related to the Sertoli cell, and to make species comparisons. For most species, measurements were taken both from stages where elongate spermatids were deeply embedded within the Sertoli cell and from stages near sperm release where elongate spermatids were in shallow crypts within the Sertoli cell. Montages, prepared from electron micrographs, were used to determine Vv% of Sertoli cell components in seminiferous tubules. Excluding the tubular lumen, the Sertoli cell occupied from a high of 43.1% (woodchuck) to a low of 14.0% (mouse) of the tubular epithelium. There was a strong negative correlation (r = -0.83; P less than 0.005) of volume occupancy of Sertoli cells with sperm production. Nuclear volume, as determined by serial reconstruction using serial thick sections, ranged from a high of 848.4 microns 3 (opossum) to a low of 273.8 microns 3 (degu). There was no correlation (r = 0.02) of nuclear volume with volume occupancy (Vv%) in the tubule. Sertoli cell volume was determined by point-counting morphometry at the electron-microscope level as the product of the nuclear size and points determined over the entire cell divided by points over the nucleus. Sertoli cell V ranged from 2,035.3 microns 3 (degu) to 7,011.6 microns 3 (opossum) and was highly correlated (r = 0.85; P less than 0.001) with nuclear size. However, there was no significant correlation between the Sertoli cell size (V) and volume occupancy (Vv%; r = 0.13) or sperm production (r = -0.21). Stereological estimates of the numerical density (Nv) of Sertoli cells ranged from a high of 101.9 x 10(6) (monkey) to a low of 24.9 x 10(6) (rabbit) cells per cm3 of testicular tissue. There was no correlation of numerical density of Sertoli cells with sperm production (r = 0.002). A negative correlation was, however, observed between the numerical density of the Sertoli cells and the Sertoli cell size (r = -0.79; P less than 0.002). Data from the present study are compared with those previously published. This is the first study to compare Sertoli cell morphological measurements using unbiased sampling techniques. Morphometric data are provided which will serve as a basis for other morphometric studies.

Animals↗

Abnormal manchette development in spermatids of azh/azh mutant mice.

A study of manchette development during spermiogenesis in azh/azh mutant mice was carried out by thin-section transmission electron microscopy with the goal of determining which of the initial steps in spermatid development are aberrant. In the homozygous mutant, spermatogenesis was quantitatively normal; but 100% of the sperm nuclei produced had abnormal shapes. The first defect, observed in steps 8-9, was the abnormal positioning of many manchette microtubules. These microtubules were directed towards regions of the plasma membrane not normally associated with manchette formation, in addition to being located at the caudal rim of the acrosome in the normal region of manchette formation. At steps 10-12, sheets of manchette microtubules were often in ectopic positions along the plasma membrane, rather than in association with the nuclear membrane as well. The fine structural appearance of the manchette was generally normal; the defect appeared to be in its positioning within the cell. In many step 8-10 spermatids nuclear invaginations and evaginations were observed, always associated with irregularities in the position of some of the manchette microtubules; these illustrate the capacity of manchette microtubules to deform nuclear shape. The nuclear irregularities remained throughout spermiogenesis. These observations are consistent with the hypothesis that the manchette is involved in at least some aspects of sperm nuclear shaping and that the improper positioning of manchette formation is a likely candidate for the primary abnormality resulting from a defective allele at the azh locus.

Animals↗

Golden hamster myoid cells during active and inactive states of spermatogenesis: correlation of testosterone levels with structure.

Myoid cells were examined quantitatively in adult golden hamsters with active spermatogenesis and compared with hamsters in which the testes were regressed due to a modification in the light-dark cycle. A detailed morphometric study was undertaken utilizing animals previously examined. The cell-surface area and volumes of most organelles were not significantly different in animals which were gonadally active as compared with regressed animals. A slight, but significant, increase in nuclear volume (31%) and a slight, but significant, decrease (28%) in cell volume were recorded for regressed animals. The total volume of pinocytotic vesicles was increased dramatically (approximately threefold) in active animals in comparison with inactive animals (P less than 0.01), indicating that an increase in non-specific transport across the myoid cell is associated with spermatogenic activity. Intravascularly injected horseradish peroxidase was capable of entering pinocytotic vesicles in both active and inactive animals. Plasma luteinizing hormone (LH) as well as plasma and testicular testosterone levels were weakly (r = 0.64, 0.68, and 0.65, respectively), but significantly (P less than 0.05), correlated with cell size. Plasma and testicular testosterone were correlated with the total volume of pinocytotic vesicles (r = 0.74 and 0.68, respectively). The data indicate that although the rat myoid cell possesses receptors for testosterone, there are few structural manifestations of the hamster myoid cell that correlate well with testosterone levels. Thus, the hamster myoid cell differs from two other hormone-responsive somatic cells in the testis, the Sertoli cell and the Leydig cell, that show dramatic structural alterations with changes in gonadal activity and striking correlations of structural features with functional measures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The effect of submandibular gland removal on testicular and epididymal parameters.

The effect of sialoadenectomy (submandibular gland removal) for four weeks duration was studied in five C3H mice and four sham-operated controls. This preliminary experiment using small numbers of animals indicated that sperm production parameters were lowered in sialoadenectomized animals although there were no significant differences between the sialodenectomized and sham-operated group. In a second experiment using larger numbers of animals, significant differences in testicular weights, epididymal weights, and testis weights were noted. These parameters were reduced only 10-14% from control levels. Epididymal sperm head counts were reduced 10% after sialoadenectomy but the two groups were not significantly different (P less than 0.05). No difference in testicular histology was observed. The present report contrasts to that of Tsutsumi et al. (1986) who indicate that submandibular removal with subsequent depletion of epidermal growth factor (EGF), is extremely deleterious (40-55% decreases in spermatid and sperm content) to the progress spermatogenesis.

Animals↗

Symplastic spermatids (sys): a recessive insertional mutation in mice causing a defect in spermatogenesis.

A line of transgenic mice that carries an insertional mutation in a gene essential for spermatogenesis is described. Males homozygous for the transgenic insert are sterile, while female homozygotes and both male and female heterozygotes exhibit normal fertility. Developing spermatids in homozygous males form prominent abnormal multinucleated syncytia (symplasts) and do not complete maturation. In addition, abnormal cytoplasmic vacuolation is commonly seen in Sertoli cells. One flank of the transgenic integration site within the genome has been cloned and used to show linkage between homozygosity for the transgene and the mutant phenotype. The flank maps to mouse chromosome 14 approximately 4 centimorgans proximal to the gene encoding esterase-10 (Es-10). As no other gene that is known to be essential for spermatogenesis has been mapped to this region of the genome and as the mutant phenotype is unique, the transgenic insert appears to affect a previously unidentified gene. We have named the mutation "symplastic spermatids" (sys).

Alleles↗

Postnatal development of the Sertoli cell barrier, tubular lumen, and cytoskeleton of Sertoli and myoid cells in the rat, and their relationship to tubular fluid secretion and flow.

The postnatal development of the Sertoli cell barrier, tubular lumen, fluid flow, and cytoskeletal elements in Sertoli and myoid cells was investigated in the Sprague-Dawley rat. With the aid of hypertonic fixatives, a barrier to the rapid entry of fluid was noted in the majority of tubules on the 15th and 16th postnatal (p.n.) days and was completely formed in all tubules prior to p.n. day 18. The actin forming the ectoplasmic specialization (ES), a cytoskeletal complex related to the occluding junctions composing the barrier, began its development during the period of initial barrier formation (16 p.n. day) and progressively attained its adult prominence. The ES developed its characteristic adult pattern and adult fluorescent intensity at about p.n. day 22. Some seminiferous tubules showed very small lumina as early as p.n. day 10. All tubules were not open until p.n. day 30. The size (diameter) of the lumen increased slowly from p.n. day 10 until p.n. day 30 when it started to increase rapidly until about p.n. day 50. Fluid flow in seminiferous tubules was detected as early as p.n. day 20 and increased in amount thereafter. Myoid cell actin filament bundles, running in parallel, were present at p.n. day 10. Actin formed a meshwork pattern characteristic of the adult on, or slightly prior to, p.n. day 22. These data indicate that there is a temporal relationship between the development of the actin cytoskeleton within the Sertoli cell and initial formation of the Sertoli cell barrier. Similarly, there is a temporal relationship between the development of the actin cytoskeleton of myoid cells and tubular fluid flow. The rapid increase in tubular lumen diameter, however, does not correlate with the initial development of Sertoli and myoid cytoskeletal elements.

Actin Cytoskeleton↗

Changes in the testicular microvasculature during photoperiod-related seasonal transition from reproductive quiescence to reproductive activity in the adult golden hamster.

The structure and permeability of the testicular microvasculature in the adult golden hamster during different phases of gonadal activity was examined. After 12 weeks of exposure to a short photoperiod (SD; 6L:18D), maximal testicular regression with over tenfold reduction in size was achieved as compared with active testes of animals maintained in long photoperiod (LD; 16L:8D). Testes weights and volumes in regressed testes were not significantly different from the values measured in animals undergoing early recrudescence (transfer from SD to LD for 1 or 2 weeks). The volume density of testicular blood vessels and their lumina did not differ significantly between fully gonadally active, fully regressed animals or those transferred from SD to LD for 2 weeks. However, in animals transferred for 1 week from SD to the stimulatory LD, the density of testicular blood vessels and vascular permeability to the endothelial tracer horseradish peroxidase were significantly increased, as compared to all other groups. An angiogenic process was observed by electron microscopy, which was initiated in the regressed gonad and which was prominent 1 week after transfer from SD to LD, but it was less conspicuous 2 weeks after transfer from SD to LD. The angiogenic process was characterized by activated developing blood vessels with a basal lamina and a lumen, which was formed by dilatation of an interendothelial space. There were two types of endothelial sprouts: the first with one layer of basal lamina, indicating true neovascularization, and the second with additional layers of basal lamina. In the latter, the presence of a superfluous basal lamina indicates that regeneration takes place along the path of old vessels. In fully regressed animals isolated basal-lamina-like structures were observed. Basal laminae are known to survive endothelial cell death, and these basal laminae later appear to serve as a scaffold for regeneration of new vessels. The rapid renewal of the testicular microvasculature under physiological stimuli suggests that the recrudescing testis of the golden hamster can be viewed as a physiological model of angiogenesis.

Animals↗

Cytoskeletal involvement in spermiation and sperm transport.

The process of spermiation and sperm transport was studied using specific inhibitors of cytoskeletal elements. Within 12-24 hr after the intratesticular injection of taxol, a compound that acts to stabilize microtubules and inhibit microtubule-related processes, an unusually large number of microtubules was seen within the body of the Sertoli cell. At the same time, transport of elements within the seminiferous epithelium was affected. At the end of stage VI of the cycle, step 19 spermatids were maintained in the deep recesses of the Sertoli cell and not transported to the rim of the seminiferous tubule lumen. At stage VIII, residual bodies remained at, or near, the rim of the tubule and were not transported to the base of the tubule. They underwent only partial degradation at this site, indicating that there may have been two phases involved in their dissolution--one autophagic and one phagocytic, but the latter did not occur since the residual bodies were not transported to Sertoli lysosomes at the base of the tubule. The observations suggest that microtubules are involved in transport processes within the seminiferous epithelium. Within 1-12 hr after the intratesticular injection of 500 microM cytochalasin D, a compound which interferes with actin-related processes, normal appearing tubulobulbar complexes were not present. The tubular portion (distal tube) of the complex did not initiate development. It was assumed that filaments (which were identified as such using NBD-phallacidin and the S-1 fragment of myosin) played an important role in the development of this portion of the complex. Cells did not eliminate cytoplasm normally, as evidenced by an enlarged cytoplasmic droplet, further emphasizing the published role for tubulobulbar complexes in cytoplasmic elimination. Although sperm were released normally from stage VIII tubules, many remained within the tubular lumen and did not traverse the duct system. Cytochalasin did not inhibit fluid secretion by the Sertoli cell, as demonstrated by efferent duct ligation, but did alter myoid cell actin cytoskeletal organization, suggesting that myoid cell contractility is primarily responsible for transport of sperm. Overall, the observations suggest that cytoskeletal activity of the Sertoli cell is important for several aspects of the spermiation process as well as sperm transport.

Actins↗

Biochemical and structural evidence for ethanol-induced impairment of testicular development: apparent lack of Leydig cell involvement.

The present study was conducted to provide biochemical and morphological evidence for ethanol-induced impairment of testicular development. The specific activities of testicular postmeiotic enzyme markers--sorbitol dehydrogenase (SDH), lactate dehydrogenase (LDH), and alpha-glycerophosphate dehydrogenase (GDH)--increased with age in CFW mice from ages 23 to 60 days, providing a biochemical measure of testicular development during puberty. Chronic ethanol treatment via liquid diets from ages 20 to 55 days resulted in decreased activities of SDH and LDH at ages 40 and 44 days, and of GDH at ages 34, 40, and 44 days. These decreases were consistent with an arrest in the developmental increase in SDH, LDH, and GDH at ages 31 +/- 0.6, 31 +/- 2.6, and 24 +/- 0.5 days, respectively. After 29 days of ethanol treatment (age 50 days), testicular weights, epididymal sperm content, and sperm motility were reduced, relative to controls, by 37, 83, and 60%, respectively (p less than 0.05). Epididymal weights were unaffected. Light microscopic evaluation of testes revealed disorganization of spermatogenesis, germ cell degeneration, decreased tubular luminal diameter, and vacuolation of Sertoli cells in ethanol-treated mice at age 50 days. Electron microscopic analysis showed that germ cell degeneration was not restricted to a specific cell type. Stage IX-XI tubules were observed in which spermatids had been retained and underwent phagocytosis within the Sertoli cell. Sertoli cells showed evidence of atypical nuclear invaginations. Sertoli cells underwent degenerative changes and were sloughed into the rete testis. However, relative Leydig cell size, as well as fractional volume occupied by the nucleus, mitochondria, and endoplasmic reticulum were unaffected by ethanol. The data (1) confirm previous findings suggesting ethanol-induced delayed testicular development; (2) suggest that certain aspects of testicular development are arrested relatively early in ethanol treatment (4-11 days); and (3) indicate that the Sertoli cell, rather than the Leydig cell, is the primary target with regard to the deleterious effect of chronic ethanol treatment on testicular maturation.

Administration, Oral↗

Sertoli cells in culture: views from the perspectives of an in vivoist and an in vitroist.

Culturing Sertoli cells has proven to be a valuable technique to study the responses of these cells under a variety of conditions. This minireview focuses on the culture system and how it has contributed to our knowledge of the capabilities of isolated Sertoli cells. In addition, it focuses on the limitations of the system and the gaps in our knowledge about Sertoli cells in culture and what the results of in vitro studies mean in the intact animal. Caution is urged in interpreting in vitro results to the intact animal without their validation in vivo.

Animals↗

Correlative morphology and endocrinology of Sertoli cells in hamster testes in active and inactive states of spermatogenesis.

The seasonally breeding golden (Syrian) hamster, which exhibits photoperiod-dependent transitions between active and inactive states of spermatogenesis, was used as a model to study Sertoli cell structure in the two extreme phases of gonadal activity. The structural parameters of the Sertoli cell and its subcellular organelles were assessed using accepted stereological procedures during active and inactive states of spermatogenesis, and the results correlated with a battery of endocrine parameters obtained from the same animals. Short photoperiod-induced testicular involution was associated with a significant decrease in virtually all morphological parameters of the Sertoli cell, including a dramatic decrease in the volumes and surface areas of the Sertoli cells and their major subcellular organelles. Sertoli cell size and surface area were significantly and positively correlated with the testicular weight, volume of the seminiferous tubule, tubular lumena, tubule diameter, and germ cell numbers. Similar correlations were recorded between the number of germ cells and nearly all subcellular parameters of the Sertoli cell. Only those structural elements that are related to degredative processes (lysosomes and lipid) did not show significant volumetric differences between gonadally active and inactive animals. The observed changes in the structural parameters of the Sertoli cells were significantly correlated with the reduction in plasma levels of FSH, LH, and testosterone and intratesticular levels of testosterone. Exposure of hamsters to a short photoperiod was also associated with an increase in concentration (femtomoles per mg protein), but a decrease in the total content (femtomoles per testis) of testicular FSH receptors. The dissociation of changes in the content and concentration of FSH receptors appears to be related to changes in basal compartment plasma membrane surface areas of the Sertoli cells during testicular regression. The striking changes in Sertoli cell morphology between active and inactive states of spermatogenesis are structural manifestations of alterations in the function of these cells in response to the concomitant endocrine changes in the testis and indicate a virtual shut-down of Sertoli cell function during short photoperiod-induced testicular regression.

Animals↗

Structure/function relationships in active and inactive hamster Leydig cells: a correlative morphometric and endocrine study.

Spermatogenesis can be turned on or off in the seasonally breeding golden (Syrian) hamster in a laboratory setting by exposure of animals to different photoperiod regimens. The present study provides the first detailed quantitative analysis of the subcellular features of hamster Leydig cells during active and inactive phases of spermatogenesis and correlates these features with the endocrine activity of the same animals. Conventional stereological principles and accepted morphometric techniques were used to determine changes in a variety of subcellular constituents of Leydig cells at the extreme phases of gonadal activity produced by maintaining adult hamsters in a long photoperiod (16 h of light, 8 h of darkness) or by exposing them to a short photoperiod (6 h of light, 18 h of darkness) for 12-13 weeks. Compared with Leydig cells from gonadally active animals, Leydig cells obtained from the regressed testis showed a significant reduction in the absolute volume of nearly all of its organelles, including nucleolus (77.0%), mitochondria (50.0%), total endoplasmic reticulum (ER) (86.4%; cisternal ER, 87.0%; tubular ER, 85.5%), lipid (84.2%), peroxisomes (82.5%), multi-vesicular bodies (71.9%), filament-rich area (95.5%), and Golgi complex (69.4%). There was also a significant reduction in organelle surface area, namely outer (76.5%) and inner (72.7%) mitochondrial membrane, total ER (85.0%), cisternal (85.3%) and tubular (84.4%) forms of ER, and Golgi complex (70.0%). The surface areas of the plasma membrane and nuclear membrane were also decreased by 58.3% and 33.7%, respectively. These results demonstrate that the short photoperiod-induced cellular inactivity of Leydig cells is associated with an overall diminution in the volume and surface area of all major organelles, not only those specifically associated with steroid biosynthesis. Virtually every structural parameter of the Leydig cell was significantly and positively correlated with plasma LH levels and with both plasma and testicular concentrations of testosterone. The total content of LH receptors per testis and per Leydig cell was reduced, but the concentration of receptors per unit area of the Leydig cell surface remained unchanged. Correlation of changes in hormonal status with alterations of all Leydig cell organelles suggests a general shut-down of cellular activity in the gonadally regressed animals, rather than a specific effect of pituitary hormones on selected cellular constituents.

Animals↗

Autoantigenic germ cells exist outside the blood testis barrier.

Preleptotene spermatocytes and spermatogonia are germ cells located outside the blood-testis barrier provided by the Sertoli cells. These cells have been found to express autoantigens accessible to circulating antibodies. Mice immunized with syngeneic testis with or without bacterial adjuvant had detectable IgG on cells at the periphery of seminiferous tubules. Sera from orchiectomized but not from testes-intact mice immunized with testis and adjuvants readily transferred similar IgG deposits to testes of normal recipients. When testis-specific antisera from orchiectomized mice and testis-intact mice were compared for their reactivity on prepuberal testicular cells, serum from orchiectomized donors had significantly higher reactivity. Ig was eluted from IgG-positive testes with acid buffer and was shown to be highly enriched in antibody to prepuberal testicular cells, confirming the Ag-specific nature of the IgG deposits. The testis IgG deposits reacted with antisera to IgG1 and IgG3 but not IgG2a or IgG2b. This finding can explain lack of association of C3 in the deposits. Only 30 to 40% of seminiferous tubules had IgG deposits and they coincided with stages 7 to 12 of the spermatogenic cycle. Thus, the expression of the autoantigens is stage specific. The in situ formation of immune complexes by circulating autoantibodies demonstrates conclusively that testis autoantigens are not completely sequestered, and the blood-testis barrier as an immunologic barrier is incomplete.

Aging↗