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PubMedDate not supplied

Fine needle aspiration cytology of a large cell calcifying Sertoli cell tumor of the testis.

A case of a large cell calcifying Sertoli cell tumor (LCCSCT) of the testis in a 7-year-old boy is presented. Fine needle aspiration (FNA) cytologic smears showed large polygonal tumor cells with abundant finely granular or vacuolated eosinophilic cytoplasm and eccentric nuclei with one distinct nucleolus. A variable amount of amorphous calcification was a constant feature. The light microscopic and ultrastructural features of the tumor cells supported a Sertoli cell origin of the tumor. This tumor is found frequently associated with complex endocrine disorders and usually has a benign course. This case, which appears to be the first such case diagnosed by FNA cytology, shows the efficacy of FNA cytology in the presurgical evaluation of testicular masses.

Biopsy, Needle↗

PubMed2004

Phagocytic removal of apoptotic spermatogenic cells by Sertoli cells: mechanisms and consequences.

More than half of differentiating spermatogenic cells undergo apoptosis before maturing into spermatozoa during mammalian spermatogenesis. These cells are selectively and rapidly eliminated through phagocytosis by Sertoli cells, a testicular somatic cell type possessing phagocytic activity. We have investigated the mechanism by which Sertoli cells specifically recognize and phagocytose apoptotic spermatogenic cells and the consequences of phagocytosis. We showed by in vitro as well as in vivo analyses that Sertoli cells recognize apoptotic spermatogenic cells through the binding of their surface receptor, class B scavenger receptor type I, to phosphatidylserine that is expressed on the surface of spermatogenic cells during apoptosis. The inhibition of phagocytosis in live animals resulted in a decrease in the number of epididymal sperm. These results suggest that phosphatidylserine-mediated phagocytosis of apoptotic spermatogenic cells by Sertoli cells is required for the efficient production of sperm.

Animals↗

PubMedDate not supplied

Growth and characterization of polarized monolayers of epididymal epithelial cells and Sertoli cells in dual environment culture chambers.

Epididymal epithelial cells isolated from mature rats and Sertoli cells isolated from 10-day-old rats were cultured in serum-free defined media on extracellular matrix impregnated filters maintained in dual environment culture chambers. Epididymal epithelial cells had a polarized appearance only when plated at high density (greater than 1 X 10(6) cells/cm2). Confluent monolayers of these cells formed a permeability barrier to inulin. Sertoli cells were columnar and highly polarized when grown on extracellular matrix-impregnated filters, cuboidal when grown on filters alone, and squamous when grown on plastic. Confluent polarized monolayers of these cells excluded the electron-dense tracer lanthanum nitrate by way of basal-tight junctions. Therefore, polarized monolayers of epididymal epithelial cells and Sertoli cells can be obtained by growing the cells at high density on extracellular matrix-impregnated permeable supports. By maintaining the monolayers in specially constructed culture chambers, the cells can develop a permeability barrier, and are able to achieve the separation of apical from basal compartments so important for their function in vivo.

Animals↗

PubMed1995

Changes in lectin binding patterns of chick primordial germ cells and Sertoli cells during sexual differentiation.

The distribution and properties of sugar residues in germ and Sertoli cells of differentiating chick gonads were examined by light microscopy using twelve different lectins. Characteristics binding patterns of ConA, RCA-1, BPA, WGA and STA were observed in germ and Sertoli cells during testicular development. BPA preferentially bound to the cytoplasm and plasma membrane of primordial germ cells (PGCs). BPA reaction appeared prior to stage 29, continued until stage 36, and completely disappeared at stage 37. This finding indicates that dynamic changes in glycoconjugates containing N-acetyl-D-galactosamine residues may occur in the cytoplasm and plasma membrane of PGCs. During the formation of testicular cords (stages 36-39), ConA, WGA, STA and RCA-I also showed a positive reaction on the cell surface of differentiating Sertoli cells. Therefore, these glycoconjugates on Sertoli cell surfaces may play an important role in testicular cord formation.

Animals↗

PubMed1989

Large-cell calcifying Sertoli cell tumor.

We report on a 20-year-old man with a left testicular mass clinically believed to be a malignant neoplasm but subsequently identified as a large-cell calcifying Sertoli cell tumor. This is a rare form of Sertoli cell tumor with unique clinical and pathological features only recently described in the literature. The neoplasm has a low malignant potential with only 1 patient known to have had metastasis. The tumor occurs primarily during the first 2 decades of life and has been associated with endocrine disorders and cardiac myxoma. The clinician should be mindful of this tumor because of its low malignant potential and the necessity to evaluate individuals for endocrine and cardiac abnormalities.

Adult↗

PubMed1989

Distribution and function of organized concentrations of actin filaments in mammalian spermatogenic cells and Sertoli cells.

Actin filaments are concentrated in specific regions of spermatogenic cells and Sertoli cells. In spermatogenic cells they occur in intercellular bridges and in the subacrosomal space. In Sertoli cells they are abundant in ectoplasmic specializations and in regions adjacent to tubulobulbar processes of spermatogenic cells. At all of these sites, the filaments are morphologically related to the plasma membrane and+or intercellular membranes, and, as in many other cell types, are arranged in either bundles or networks. In at least two of the locations just indicated (ectoplasmic specializations and intercellular bridges), elements of the ER are closely related to the actin filaments. In tubulobulbar complexes, ER is present but is more distantly related to the filaments. Elements of the ER, when present, may serve a regulatory function. The filaments in ectoplasmic specializations and in regions adjacent to tubulobulbar processes of spermatogenic cells are suspected to be involved with the mechanism by which intercellular junctions are established, maintained, and degraded. In intercellular bridges, actin filaments may serve to reinforce and perhaps regulate the size of the cytoplasmic connections between differentiating germ cells. Filaments in the subacrosomal space may serve as a linking network between the acrosome and nucleus and may also be involved in the capping process. Because of the possibility that the actin filaments discussed before may be related to specific membrane domains involved with intercellular or interorganelle attachment, and that changes in these membrane domains are prerequisite to processes such as sperm release, turnover of the blood-testis barrier, formation of the acrosome, and coordination of spermatogenic cell differentiation, an understanding of exactly how these actin filaments are related to elements in the membrane and how this interaction is controlled is fundamental to our understanding, and perhaps our manipulating, of male fertility. I suspect that working out the molecular organization of these actin filament-containing sites and determining how their organization is controlled will be the major focus of research in this field over the next few years.

Actins↗

PubMed1992

Large cell calcifying Sertoli cell tumor of the testis.

We report on a patient with a large cell calcifying Sertoli cell tumor of the testis and review the literature of this recently described rare subtype of Sertoli cell tumor. Twenty-one cases, including ours, have been reported in the literature. Six of twenty cases (28%) had clinically evident endocrine abnormalities and eight of twenty-one cases (38%) were bilateral. This tumor has a low malignant potential with only one patient known to have metastatic disease.

Calcinosis↗

PubMed2006

Prepubertal testis development relies on retinoic acid but not rexinoid receptors in Sertoli cells.

Sertoli cells (SC) are instrumental to stem spermatogonia differentiation, a process that critically depends on retinoic acid (RA). We show here that selective ablation of RA receptor alpha (RARalpha) gene in mouse SC, singly (Rara(Ser-/-) mutation) or in combination with RARbeta and RARgamma genes (Rara/b/g(Ser-/-) mutation), abolishes cyclical gene expression in these cells. It additionally induces testis degeneration and delays spermatogonial expression of Stra8, two hallmarks of RA deficiency. As identical defects are generated upon inactivation of RARalpha in the whole organism, our data demonstrate that all the functions exerted by RARalpha in male reproduction are Sertoli cell-autonomous. They further indicate that RARalpha is a master regulator of the cyclical activity of SC and controls paracrine pathways required for spermatogonia differentiation and germ cell survival. Most importantly, we show that the ablation of all RXR (alpha, beta and gamma isotypes) in SC does not recapitulate the phenotype generated upon ablation of all three RARs, thereby providing the first evidence that RARs exert functions in vivo independently of RXRs.

Aging↗

PubMed1991

Large cell calcifying Sertoli cell tumor of the testis. A clinicopathologic, immunohistochemical, and ultrastructural study of two cases.

The clinicopathologic, immunohistochemical, and electron microscopic study of two patients with large cell calcifying Sertoli cell tumors (LCCSCT) of the testis is reported to elucidate the histogenesis of this rare tumor. Both tumors occurred in young individuals (16 and 32 years); case 1 was found incidentally, and the patient in case 2 presented with a 3-4-week history of testicular pain. Evidence of testosterone production was demonstrated in one case. In the same case, at the ultrastructural level Charcot-Böttcher crystalloids were observed. These data support previous reports that LCCSCT shows Sertoli cell differentiation.

Adolescent↗

PubMed1999

mRNAs encoding a von Ebner's-like protein and the Huntington disease protein are induced in rat male germ cells by Sertoli cells.

The success of spermatogenesis is dependent upon closely coordinated interactions between Sertoli cells and germ cells. To identify specific molecules that mediate interactions between somatic cells and germ cells in the rat testis, Sertoli cell-germ cell co-cultures and mRNA differential display were used. Two cDNAs, clone 1 (660 nucleotides) and clone 2 (390 nucleotides) were up-regulated when Sertoli cells were co-cultured with pachytene spermatocytes or round spermatids. Northern blot analyses confirmed the differential display expression patterns. Sequence analyses indicated that clone 1 was similar to a von Ebner's gland protein (87% at the nucleotide level and 80% at the amino acid level) and clone 2 was identical to a region of the Huntington disease protein. The von Ebner's-like protein mRNA was induced after 4 h of co-culture, while the Huntington disease protein required 18 h of co-culture for expression. The von Ebner's-like protein was induced in germ cells by a secreted Sertoli cell factor(s) smaller than 10 kDa that is sensitive to freezing and thawing or boiling. The Huntington disease protein was induced in germ cells by a Sertoli cell secreted factor(s) larger than 10 kDa which survives freezing and thawing, but is inactivated by boiling.

Amino Acid Sequence↗

PubMed1999

Malignant large cell calcifying Sertoli cell tumor of the testis (LCCSCTT). Report of a case in an elderly man and review of the literature.

Malignant Large Cell Calcifying Sertoli Cell Tumor of the Testis (LCCSCTT) is a rare histological variant of sex cordstromal tumors. It usually arises in young males, sometimes is associated with endocrine abnormalities and has a benign course. It is exceptional in elderly men and the outcome is rarely fatal. We report a case of LCCSCTT in a 73 year-old man with fatal outcome. The tumor involved the right testis and several areas of the tunica albuginea were grossly invaded. Serum levels of HCG, LH and testosterone were normal. Lymphoangiography performed after orchiectomy showed an involvement of the iliac and preaortic lymph nodes. X-ray of the chest showed no lung metastases. A thorough study of the light microscopic, immunohistochemical and ultrastructural appearances was performed. Immunohistochemistry revealed positivity to vimentin, S-100 and NSE. Our observations confirm the previous findings concerning malignant LCCSCTT and point out the histogenesis of the tumor from Sertoli cells.

Age of Onset↗

PubMed2005

In vivo analysis of phagocytosis of apoptotic cells by testicular Sertoli cells.

Sertoli cells, a somatic cell type present within the seminiferous tubules of testes, are responsible for the phagocytic elimination of apoptotic spermatogenic cells. We here established an in vivo assay system that enables us to quantitatively analyze Sertoli cell phagocytosis of apoptotic cells in testes of live mice. Apoptotic cells were injected into the seminiferous tubules of spermatogenic cell-depleted mice, and the occurrence of phagocytosis by Sertoli cells was examined by histochemically analyzing testis sections or dispersed testicular cells. We reproducibly observed similar levels of phagocytosis in either examination, and the ratio of Sertoli cells that engulfed injected apoptotic cells was almost the same between the two examinations. These results indicated that a quantitative in vivo assay system was established using the seminiferous tubules of live mice as 'test tubes.' We then determined the requirements for Sertoli cell phagocytosis of apoptotic cells using this assay. For this purpose, apoptotic cells were injected together with various phagocytosis inhibitors, and the extent of phagocytosis by Sertoli cells was determined. The results revealed that Sertoli cells phagocytose apoptotic cells in a manner dependent on class B scavenger receptor type I (SR-BI) of Sertoli cells and phosphatidylserine exposed at the surface of target cells, as previously observed in vitro using primary cultures of dispersed rat testicular cells. Furthermore, the amount of SR-BI in Sertoli cells increased after injection of apoptotic cells into the seminiferous tubules, suggesting a positive feedback regulation of the expression of this phagocytosis receptor.

Animals↗

PubMed1997

Human Leydig cells and Sertoli cells are producers of interleukins-1 and -6.

Interleukins (IL)-1 and -6 have been shown to be produced by several categories of cells in the rat testis and involved in the paracrine control of testicular function. Evidence of high amounts of IL-1 have been shown in the human testis, but nothing is known about its cellular origin. Furthermore, to our knowledge, the presence of IL-6 in the human testis has not yet been investigated. Therefore, the present study was aimed at identifying IL-1 and -6 expression and production within the human testis, using RT-PCR, bioassays, and enzyme linked immunosorbent assays. We demonstrated that IL-1 and -6 messenger RNA and proteins were produced constitutively in vitro by human Leydig cell- and Sertoli cell-enriched preparations. FSH only stimulated IL-6 production by Sertoli cell-enriched preparations, but increased the release of both IL-1 and -6 in germ cell-depleted Sertoli cell cultures. In addition, lipopolysaccharides and latex beads enhanced the production of both cytokines by Sertoli cell cultures, whereas human chorionic gonadotropin and lipopolysaccharides enhanced the release of both cytokines by Leydig cells. Enzyme linked immunosorbent assays and neutralization experiments revealed that human Sertoli cells produce essentially the alpha form of IL-1, whereas both forms, alpha and beta, are present in Leydig cells. The demonstration that human Leydig and Sertoli cells produce IL-1 and -6 under the control of gonadotropin hormones and exogenous factors, opens the possibility to study the involvement of these cytokines in the control of testis function, in normal and pathological conditions in men.

Adult↗

PubMed2005

Follicular cells acquire sertoli cell characteristics after oocyte loss.

Although it has been suggested that in mammals the loss of female germ cells may induce the masculinization of the ovarian compartment, there has been as yet no conclusive demonstration. To directly address that question, the present study has been designed to determine the fate of follicular cells after oocyte loss. Using gamma-irradiation to selectively deplete oocytes in nongrowing follicles in female rats, we show that follicular cells in oocyte-depleted follicles survive, proliferate, and subsequently acquire morphological characteristics of Sertoli cells: elongated cytoplasm, basal location of the nucleus, and specific Sertoli cell junctions, the ectoplasmic specializations. These Sertoli-like cells express, however, the female-specific marker FOXL2 (Forkhead L2) but not the male sex-specific marker SOX-9 (Sry-type high-mobility-group box transcription factor-9) underlying the maintenance of molecular characteristics of granulosa cells. Before transdifferentiating into Sertoli-like cells, follicular cells of oocyte-depleted follicles initiate the expression of anti-Mullerian hormone and inhibin alpha-subunit that are typically synthesized by granulosa cells from the onset of follicular growth. Experimental modifications of the endocrine balance of the irradiated females show that there is a close relationship between plasma FSH levels and the occurrence of Sertoli-like cells. In addition to providing experimental evidence for the crucial role of the oocyte in granulosa cell phenotype maintenance, these results emphasize that the transdifferentiation of granulosa cells into Sertoli cells occurs in a multistep fashion, requiring the maturation of granulosa cells and depending on the endocrine milieu.

Animals↗

PubMed2002

In situ demonstration of both TUNEL-labeled germ cell and Sertoli cell in the cimetidine-treated rats.

Cimetidine has caused dysfunction in the male reproductive system. In the rat testis, intratubular alterations and loss of peritubular tissue due to peritubular myoid cell death by apoptosis have been recently shown. Thus, the aim of this study is to evaluate which cells of the seminiferous epithelium have been affected and/or died by apoptosis after the treatment with cimetidine. For this purpose, an experimental group containing five male albino Wistar rats received intraperitoneal injections of cimetidine (50 mg/kg body weight) during 52 days. The testes were fixed with 4% buffered formaldehyde and were embedded in paraffin. For detection of DNA breaks (apoptosis) in the cells of the seminiferous epithelium, the testicular sections were treated by the TUNEL method (Apop-Tag Plus Peroxidase Kit). In the tubules affected by cimetidine, altered peritubular tissue, including the presence of TUNEL labeling in the myoid peritubular cells, were usually found. In these tubules, the seminiferous epithelium exhibited low density of germ cells and TUNEL-positive labeling in the germ cells of the basal compartment. The concomitant staining in both germ cells of the basal compartment and late spermatids suggest a sensitivity of these cells in the damaged tubules. Besides germ cells, TUNEL-positive Sertoli cells were also found in the injured seminiferous tubules. Thus, a relationship between dying germ cells and Sertoli cell damage and/or death must be considered in tubules where peritubular tissue has been affected by toxicants.

Animals↗

PubMed1994

[Utilization of linoleate and alpha-linolenate in peritubular cells and Sertoli cells in culture].

The capacity of cultured peritubular cells to synthesize long-chain polyunsaturated fatty acids (PUFA) from the essential fatty acid (EFA) precursors 18:2n-6 and 18:3n-3 was tested, and compared to the PUFA biosynthesis in Sertoli cells. The concentrations of each EFA required to obtain maximal incorporation into membrane lipids were determined. The two EFA were added to the culture medium as free fatty acids complexed to albumin in a molar ratio of 12:1. When the substrates were added individually, the maximal levels of biosynthesis in peritubular cells were obtained with 0.70 microgram/ml of 18:2n-6 or 18:3n-3 in culture medium. With Sertoli cells, the concentration of 0.70 micrograms/ml linoleate or of 2.00 micrograms/ml alpha-linolenate in culture medium appeared to correspond to levels required for maximal incorporation and utilization of the n-6 PUFA or n-3 PUFA. Incorporation and metabolic utilization were always more important in cultured Sertoli cells than in cultured peritubular cells. The peritubular cell appeared to incorporate linoleate les efficiently than alpha-linolenate at identical concentrations. In agreement with observations in other cell systems (15), we found a preferential utilization of 18:3n-3 over 18:2n-6 by the delta 6 desaturase in the peritubular cell and in the Sertoli cell.

Animals↗

PubMed1987

Peritubular cells influence Sertoli cells at the level of translation.

Conditioned medium from cultured peritubular cells (PTCM) was capable of increasing the incorporation of amino acids into acid-precipitable material in cultured Sertoli cells, while the incorporation of uridine into acid-precipitable material was unaffected. PTCM did not influence intracellular cAMP accumulation in a manner similar to follicle-stimulating hormone (FSH). PTCM was able to stimulate androgen-binding protein (ABP) secretion by Sertoli cells even in the presence of a maximal dose of FSH. PTCM increased the rate at which peptides are elongated 5-fold over control medium or medium from control fibroblasts. These studies indicate that peritubular cells influence Sertoli cells through different mechanisms than FSH and exert their influence, at least in part, at the level of translation by increasing the rate of peptide elongation.

Androgen-Binding Protein↗

PubMed2001

Evidence that Sry is expressed in pre-Sertoli cells and Sertoli and granulosa cells have a common precursor.

The expression of Sry in the undifferentiated, bipotential genital ridges of mammalian XY fetuses initiates testis development and is hypothesized to do so by directing supporting cell precursors to develop as Sertoli cells and not as granulosa cells. To directly test this hypothesis, transgenic mice expressing EGFP under the control of the Sry promoter were produced. After establishing that the transgene was expressed in fetal gonads similarly to endogenous Sry, the spatial and temporal expression of the Sry-EGFP transgene was investigated in developing gonads by using confocal microscopy and immunofluorescent histochemistry. This analysis indicated: (1) Sry is first expressed in cells located centrally in the genital ridge and then later in cells located at the cranial and caudal poles, (2) Sry is expressed exclusively in pre-Sertoli cells in the urogenital ridge, and (3) Sertoli and granulosa cells develop from a common precursor. These results support the hypothesis that Sry initiates testis differentiation by directing the development of supporting cell precursors as Sertoli rather than granulosa cells. Furthermore, the Sry expression pattern explains the nonrandom distribution of testicular and ovarian tissue in mammalian ovotestes.

Animals↗