scholarly journals Correlation between inhibin secretion and damage of seminiferous tubules in a model of experimental autoimmune orchitis

2001 ◽  
Vol 170 (1) ◽  
pp. 113-120 ◽  
Author(s):  
MO Suescun ◽  
MO Suescun ◽  
L Lustig ◽  
RS Calandra ◽  
RS Calandra ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Inverse Correlation ◽  
Inhibin B ◽  
Alpha Subunit ◽  
Germinal Epithelium ◽  
Seminiferous Tubules ◽  
Positive Staining ◽  
Testis Weight ◽  
Autoimmune Orchitis ◽  
Experimental Autoimmune

The aim of the present study was to evaluate inhibin secretion in rats with autoimmune orchitis. As we have previously described, experimental autoimmune orchitis (EAO) induced in rats by active immunization with testis homogenate and adjuvants is characterized by an interstitial mononuclear cell infiltrate and sloughing of the germinal epithelium. At 120 days after the first immunization 60% of the rats exhibited a severe orchitis with large areas of aspermatogenic seminiferous tubules in which only spermatogonia and Sertoli cells with cytoplasmic vacuolization remained attached to the tubular wall. None of the untreated (N) or control (C) rats revealed pathological alterations. Sixty percent decrease in testis weight was observed in rats with EAO compared with N or C groups. A 3-fold increase in serum FSH levels was observed in rats with EAO compared with N or C groups (19.8+/-3.7 vs 5.6+/-0.3 and 5.9+/-0.1 ng/ml respectively). A significant decrease in inhibin B levels was observed in rats with EAO when compared with N or C groups (40+/-4.6 vs 207+/-38.8 and 221.4+/-28.6 pg/ml respectively). An inverse correlation between inhibin B and FSH serum levels and a direct correlation between inhibin B and testis weight were found. Strong expression of the inhibin alpha-subunit in Sertoli cells of untreated and control rats was observed; this subunit was undetectable or poorly detectable in rats with orchitis. Positive staining for the inhibin alpha-subunit was also observed in Leydig cells of all groups studied. In conclusion, using a model of autoimmune orchitis our results show that circulating inhibin B levels and inhibin alpha-subunit expression in Sertoli cell cytoplasm closely correlate with the degree of damage of the germinal epithelium.

scholarly journals Pachytene spermatocytes in co-culture inhibit rat Sertoli cell synthesis of inhibin beta B-subunit and inhibin B but not the inhibin alpha-subunit

2002 ◽  
Vol 172 (3) ◽  
pp. 565-574 ◽  
Author(s):  
RJ Clifton ◽  
L O'Donnell ◽  
DM Robertson
Keyword(s):  
Mrna Expression ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Inhibin B ◽  
Alpha Subunit ◽  
Subunit Mrna ◽  
B Subunit ◽  
Subunit Expression ◽  
Pachytene Spermatocytes

This study investigates the effects of spermatogenic germ cells on inhibin alpha-subunit and beta B-subunit expression, and inhibin alpha-subunit and inhibin B production by rat Sertoli cells in vitro. Sertoli cells isolated from 19-day-old rats were cultured for 48 h at 32 degrees C, in the presence or absence of FSH (2.3-2350 mIU/ml), and in the presence of pachytene spermatocytes, round spermatids or cytoplasts of elongated spermatids purified from adult rat testis by elutriation and density gradient separation. Sertoli cell secretion of inhibin alpha-subunit and inhibin B, as measured by immunoassay, was dose-dependently stimulated by FSH (maximal stimulation 13- and 2-fold, respectively). Round spermatids or cytoplasts co-cultured with Sertoli cells had no effect on basal or FSH-induced secretion of inhibin alpha-subunit or inhibin B. When Sertoli cells were co-cultured with pachytene spermatocytes, inhibin alpha-subunit secretion was unaltered, while inhibin B secretion was suppressed in a cell concentration-dependent manner to reach a maximal suppression of 45% compared with Sertoli cells alone (P<0.01). A similar suppression in inhibin B was still observed (64% of Sertoli cells alone) when the pachytene spermatocytes were separated from Sertoli cells by a 0.45 microm pore membrane barrier in bicameral chambers. Pachytene spermatocytes also suppressed FSH-induced inhibin B levels in Sertoli cell co-cultures and this suppression was attributed to a decrease in basal inhibin B production rather than a change in FSH responsiveness. Quantitation of Sertoli cell inhibin alpha- and beta B-subunit mRNA by quantitative (real-time) PCR demonstrated that pachytene spermatocytes did not alter Sertoli cell alpha-subunit mRNA expression, but significantly (P<0.01) suppressed basal and FSH-induced beta B-subunit mRNA expression to a similar degree to that seen with inhibin B protein levels. It is concluded that pachytene spermatocytes in vitro suppress Sertoli cell inhibin B secretion via factor-mediated suppression of inhibin beta B-subunit expression. These findings support the hypothesis that specific germ cell types can influence inhibin B secretion by the testis independent of FSH regulation.

Secretion of transferrin in ovine seminiferous tubule cell cultures in response to FSH: influence of breed, season of birth and age of lambs

1993 ◽  
Vol 5 (1) ◽  
pp. 83 ◽  
Author(s):  
C Monet-Kuntz ◽  
I Fontaine
Keyword(s):  
Cell Cultures ◽  
Dose Response ◽  
Sertoli Cells ◽  
Seminiferous Tubule ◽  
Seminiferous Tubules ◽  
Testis Weight ◽  
Season Of Birth ◽  
Tubule Cell ◽  
Response Curves ◽  
Testicular Weight

The response of lamb Sertoli cells to follicle stimulating hormone (FSH) was investigated by measuring transferrin secretion in seminiferous tubule cell cultures throughout the non-pubertal and the prepubertal periods. Cells could be cultured from birth until they attained a testicular weight of 19 g. The characteristics of individual dose-response curves were compared according to the breed, season of birth and testicular weight of the lambs. At the same season of birth and within a given testis weight range, dose-response curves of Romanov and Ile-de-France lambs were similar. Within a given testis weight range, spring-born animals exhibited a higher maximal transferrin secretion than autumn-born lambs, but the ED50 was similar. The main factor of variation of the dose-response curve parameters was the testicular weight of the lambs: the amplitude of FSH response increased 3-fold from a testicular weight of 6 g onwards, i.e. from the appearance of spermatogonia in seminiferous tubules. The ED50 increased 5-fold from 11 g onwards, i.e. from the beginning of the prepubertal period. Thus, Sertoli cells become less sensitive to FSH as spermatogenesis develops in seminiferous tubules. This phenomenon is largely the result of higher phosphodiesterase activity and is greatly reduced by 1-methyl-3-isobutyl-xanthine (MIX).

scholarly journals Involvement of CD44 in leukocyte recruitment to the rat testis in experimental autoimmune orchitis

Reproduction ◽  
2005 ◽  
Vol 129 (5) ◽  
pp. 603-609 ◽  
Author(s):  
V A Guazzone ◽  
B Denduchis ◽  
L Lustig
Keyword(s):  
Fluorescence Intensity ◽  
Mean Fluorescence Intensity ◽  
Mononuclear Cells ◽  
Leukocyte Recruitment ◽  
Seminiferous Tubules ◽  
Sprague Dawley ◽  
Adult Rats ◽  
Peripheral Blood Mononuclear ◽  
Autoimmune Orchitis ◽  
Experimental Autoimmune

Experimental autoimmune orchitis (EAO) is characterized by an interstitial mononuclear cell infiltrate and a severe lesion of the seminiferous tubules with germ cells that undergo apoptosis and sloughing. The aim of this study was to determine the role of CD44 in testicular leukocyte recruitment in EAO. The biological functions of CD44 have been attributed to the generation of a functionally active hyaluronan-binding phenotype. Orchitis was induced in Sprague–Dawley adult rats by active immunization with an emulsion of testicular homogenate and complete Freund’s adjuvant using Bordetella pertussis as co-adjuvant. Control rats (C) injected with saline and adjuvants and normal (N) untreated rats were also studied. CD44 expression was analyzed by flow cytometry in peripheral blood mononuclear cells (PBMC) and lymph node cells isolated from rats at different times after the first immunization. We observed an increase in the mean fluorescence intensity of both samples in the C and experimental (E) groups only after the immunization period. A significant decrease in percentage of CD44 + PBMC and in mean fluorescence intensity was observed in rats with orchitis compared with the C group. By in vitro hyaluronic acid-binding assay we demonstrated that the percentage of PBMC adhesion was higher in the E group compared with the C and N groups. By immunohistochemistry, we observed a significant increase in the number of CD44 + cells in the testicular interstitium of rats with severe orchitis compared with the N and C groups. These results suggested that the CD44 molecule is involved in the homing of lymphomonocytes into the testes of rats with autoimmune orchitis.

scholarly journals Serum inhibin B, FSH, LH and testosterone levels before and after human chorionic gonadotropin stimulation in prepubertal boys with cryptorchidism

2002 ◽  
Vol 147 (1) ◽  
pp. 95-101 ◽  
Author(s):  
P Christiansen ◽  
AM Andersson ◽  
NE Skakkebaek ◽  
A Juul
Keyword(s):  
Chorionic Gonadotropin ◽  
Human Chorionic Gonadotropin ◽  
Sertoli Cells ◽  
Cell Function ◽  
Serum Levels ◽  
Inhibin B ◽  
Seminiferous Tubules ◽  
Bilateral Cryptorchidism ◽  
Prepubertal Boys ◽  
Baseline Levels

BACKGROUND: Several studies have indicated that cryptorchidism is associated with degenerative changes in both Sertoli cells and germ cells. The gonadal peptide hormone inhibin B reflects Sertoli cell function. Low inhibin B levels are found in a large portion of formerly cryptorchid men who show compromised seminiferous tubule function. It is not known if inhibin B can be used to demonstrate early damage of seminiferous tubules in prepubertal boys with cryptorchidism. METHODS: We investigated the relationship between serum levels of inhibin B, testosterone, FSH and LH in 62 prepubertal boys with uni- and bilateral cryptorchidism. Furthermore, we investigated the changes in serum levels of inhibin B and the corresponding changes in serum levels of FSH, LH and testosterone during a short course (3 weeks) of human chorionic gonadotropin (hCG) injections in 18 of these cryptorchid boys. RESULTS: In the 62 prepubertal boys with uni- or bilateral cryptorchidism there were no significant differences in baseline levels (median and range) of inhibin B (88 (20-195) pg/ml vs 78 (35-182) pg/ml; not significant), LH (0.08 (<0.05-0.99) IU/l vs 0.06 (<0.05-1.61) IU/l; not significant) and FSH (0.60 (0.08-3.73) IU/l vs 0.85 (0.25-2.55); not significant) compared with 156 healthy prepubertal boys, and there were no differences in hormonal levels between boys with uni- or bilateral cryptorchidism. There was no correlation between baseline levels of inhibin B and FSH. In boys younger than 9 years, we found no correlation between baseline levels of inhibin B and LH whereas, in boys older than 9 years, baseline levels of inhibin B were positively correlated to baseline LH (Spearman rank correlation coefficient ((R(s))=0.58, P=0.03). Treatment with hCG (1500 IU intramuscularly twice weekly for 3 weeks) resulted in descensus of testes in 9 out of 18 patients. In all boys but one, irrespective of age, hCG induced a marked increase in testosterone into the adult range (from undetectable to 21.8 (7.0-35.4) nmol/l; P<0.001) and completely suppressed FSH and LH levels. Serum levels of inhibin B increased significantly from 116 (50-195) pg/ml to 147 (94-248) pg/ml (P<0.05), but not uniformly. The increase in serum levels of inhibin B was inversely correlated to baseline inhibin B (Rs=-0.52, P=0.03) and baseline FSH (R(s)=-0.59, P<0.01). CONCLUSIONS: We therefore suggest that, in the prepubertal testes, inhibin B is secreted from the prepubertal Sertoli cells following hCG, whereas early pubertal testes with more differentiated Sertoli cells are not able to secrete inhibin B in response to hCG stimulation, perhaps due to lack of germ cell-derived betaB-subunits. We found (a) normal inhibin B levels in prepubertal boys with uni- or bilateral cryptorchidism, (b) that hCG stimulated testosterone markedly and suppressed FSH and LH levels and (c) that hCG treatment stimulated inhibin B levels in the youngest cryptorchid boys. In the oldest prepubertal boys no hCG-induced changes in inhibin B were shown.

Morphological study of the effects of an GnRH agonist on the canine testis after 4 months of treatment and recovery

1987 ◽  
Vol 116 (3) ◽  
pp. 413-417 ◽  
Author(s):  
D. Dubé ◽  
A. Assaf ◽  
G. Pelletier ◽  
F. Labrie
Keyword(s):  
Gnrh Agonist ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Lipid Droplets ◽  
Seminiferous Tubules ◽  
Testis Weight ◽  
Electron Microscope Level ◽  
Reversible Method ◽  
Normal Spermatogenesis ◽  
Cessation Of Treatment

Abstract. After 4 months of treatment of adult male dogs with the GnRH agonist (GnRH-A) [D-Trp6]GnRH ethylamide, the seminiferous tubules contained only type A and B spermatogonia, Sertoli cells, and rare primary spermatocytes, thus causing a 64% decrease in testis weight. At the electron microscope level, Sertoli cells showed an increase in phagosomes and lipid droplets. Leydig cells were markedly atrophied with the accumulation of lipid droplets and showed a pre-dominance of mitochondria with lamellar instead of vesicular cristae. Four months after cessation of treatment with GnRH-A, a complete return to normal spermatogenesis and Leydig cell morphology was observed. The full reversibility of spermatogenesis in the dog after chronic GnRH-A treatment suggests that this well-tolerated peptide could be used as a reversible method of male contraception.

Ontogeny of inhibin secretion in the rat testis: secretion of inhibin-related proteins from fetal Leydig cells and of bioactive inhibin from Sertoli cells

1997 ◽  
Vol 155 (1) ◽  
pp. 27-34 ◽  
Author(s):  
J Noguchi ◽  
H Hikono ◽  
S Sato ◽  
G Watanabe ◽  
K Taya ◽  
...  
Keyword(s):  
Molecular Mass ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Molecular Size ◽  
Interstitial Cells ◽  
Alpha Subunit ◽  
Seminiferous Tubules ◽  
Fetal Life ◽  
Neonatal Rats ◽  
Related Proteins

The ontogeny of inhibin secretion in the testis of rats was investigated. Testicular localization, content of immunoactive and bioactive inhibin and its molecular size in fetal and neonatal rats (from 16 days of gestation to 5 days of age) were determined. Strong immunostaining with an antiserum against a polypeptide of porcine inhibin alpha-subunit was noted in testicular interstitial cells from 16 days of gestation. Co-localization of inhibin alpha-subunit and 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) was observed in the interstitial cells until 2 days of age. Immunoreactive inhibin alpha-subunit in the interstitial tissue had disappeared by 5 days of age, although 3 beta HSD-positive cells were still detected. Weak immunostaining for the inhibin alpha-subunit was detected in the seminiferous tubules, probably in the cytoplasm of Sertoli cells, from 20 days of gestation onward. No inhibin alpha-subunit immunostaining was observed in germ cells throughout the experimental period. Testicular inhibin was detected at 16 days of gestation (49.5 +/- 6.7 pg per testis) by RIA. Testicular immunoreactive inhibin showed a tendency to increase during fetal life and levels were maintained at a similar value after birth (697.0 +/- 46.9 pg per testis at 5 days of age). Inhibin bioactivity and its molecular size in testicular homogenate was examined at 17 days of gestation and 0 and 5 days of age. Although no bioactivity was detected at 17 days of gestation, bioactivity was noted at 0 and 5 days of age (177.7 and 1303.9 pg per testis respectively). Immunoblot analysis with antiserum against inhibin alpha-subunit revealed only approximately 40 kDa molecular masses in the testis at 17 days of gestation, probably inhibin-related proteins, but not inhibin. At 0 and 5 days of age, a protein of 30 kDa molecular mass, possibly inhibin, was detected as well as material of approximately 40 kDa molecular mass. FSH in the plasma was first detected at 19 days of gestation (1197.0 ng/l), increased towards birth, and thereafter decreased (4588.5 +/- 572.3 ng/l at 21 days of gestation and 2400.0 +/- 179.6 ng/l at 5 days of age). These results indicate that Leydig cells in fetal and neonatal rats produce inhibin-related substances with no inhibin bioactivity, whereas Sertoli cells begin to produce inhibin during the perinatal period as a possible regulator of FSH secretion.

scholarly journals High Throughput scRNA-Seq Provides Insights Into Leydig Cell Senescence Induced by Experimental Autoimmune Orchitis: A Prominent Role of Interstitial Fibrosis and Complement Activation

2022 ◽  
Vol 12 ◽  
Author(s):  
Yinchuan Li ◽  
Panpan Mi ◽  
Jiabao Wu ◽  
Yunge Tang ◽  
Xiaohua Liu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
High Throughput ◽  
Interstitial Fibrosis ◽  
Glutathione Metabolism ◽  
Seminiferous Tubules ◽  
Sex Characteristics ◽  
Androgen Synthesis ◽  
Chemokine Signaling ◽  
Autoimmune Orchitis ◽  
Experimental Autoimmune

Leydig cells (Lc), located in the interstitial space of the testis between seminiferous tubules, produce 95% of testosterone in male individuals, which is pivotal for male sexual differentiation, spermatogenesis, and maintenance of the male secondary sex characteristics. Lc are prone to senescence in aging testes, resulting in compromised androgen synthesis capability upon aging. However, little is known about whether Lc undergo senescence in a chronic inflammatory environment. To investigate this question, mouse models of experimental autoimmune orchitis (EAO) were used, and Lc were analyzed by high throughput scRNA-Seq. Data were screened and analyzed by correlating signaling pathways with senescence, apoptosis, androgen synthesis, and cytokine/chemokine signaling pathways. EAO did induce Lc senescence, and Lc senescence in turn antagonized androgen synthesis. Based on the correlation screening of pathways inducing Lc senescence, a plethora of pathways were found to play potential roles in triggering Lc senescence during EAO, among which the Arf6 and angiopoietin receptor pathways were highly correlated with senescence signature. Notably, complement and interstitial fibrosis activated by EAO worsened Lc senescence and strongly antagonized androgen synthesis. Furthermore, most proinflammatory cytokines enhanced both senescence and apoptosis in Lc and spermatogonia (Sg) during EAO, and proinflammatory cytokine antagonism of the glutathione metabolism pathway may be key in inducing cellular senescence during EAO.

Testicular Degeneration and Necrosis Induced by Dietary Cobalt

1985 ◽  
Vol 22 (6) ◽  
pp. 610-616 ◽  
Author(s):  
D. E. Corrier ◽  
H. H. Mollenhauer ◽  
D. E. Clark ◽  
M. F. Hare ◽  
M. H. Elissalde
Keyword(s):  
Sertoli Cells ◽  
Leydig Cells ◽  
Giant Cells ◽  
Seminal Vesicles ◽  
Germinal Epithelium ◽  
Seminiferous Tubules ◽  
Multinucleated Giant Cells ◽  
Necrotic Debris ◽  
Testicular Degeneration

Dietary cobalt (265 ppm Co) induced polycythemia and consistent degenerative and necrotic lesions in the seminiferous tubules of rats. Cyanosis and engorgement of testicular vasculature on day 35 and thereafter was followed on day 70 by degenerative and necrotic changes in the germinal epithelium and Sertoli cells. Spermatogonia, primary spermatocytes and round spermatids were markedly affected, while elongated spermatids, spermatozoa, and Sertoli cells were more resistant. Damaged tubules, often present side by side with normal tubules, contained multinucleated giant cells composed of degenerated and necrotic spermatocytes and/or spermatids, sloughed germinal and Sertoli cells, and calcified necrotic debris. Necrotic tubules were frequently collapsed and devoid of epithelium except for occasional spermatogonia and surviving Sertoli cells. Lesions were not observed in the Leydig cells, cauda epididymis or seminal vesicles.

1509: Adeno-Associated Virus-Mediated Human IL-10 Gene Transfer Suppresses the Development of Experimental Autoimmune Orchitis

2005 ◽  
Vol 173 (4S) ◽  
pp. 409-409
Author(s):  
Masami Watanabe ◽  
Atsushi Nagai ◽  
Norihiro Kusumi ◽  
Yasutomo Nasu ◽  
Hiromi Kumon ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Adeno Associated Virus ◽  
Autoimmune Orchitis ◽  
Experimental Autoimmune

Defects in the regulatory clearance mechanisms favor the breakdown of self-tolerance during spontaneous autoimmune orchitis

2009 ◽  
Vol 296 (3) ◽  
pp. R743-R762 ◽  
Author(s):  
R.-Marc Pelletier ◽  
Suk Ran Yoon ◽  
Casimir D. Akpovi ◽  
Emil Silvas ◽  
María Leiza Vitale
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Plasma Membranes ◽  
Fas Ligand ◽  
Inflammatory Responses ◽  
Apoptotic Cell ◽  
Self Tolerance ◽  
Tnf Α ◽  
Fas L ◽  
Autoimmune Orchitis

We identified aberrations leading to spontaneous autoimmune orchitis (AIO) in mink, a seasonal breeder and natural model for autoimmunity. This study provides evidence favoring the view that a malfunction of the clearance mechanisms for apoptotic cell debris arising from imbalances in phagocyte receptors or cytokines acting on Sertoli cells constitutes a major factor leading to breakdown of self-tolerance during spontaneous AIO. Serum anti-sperm antibody titers measured by ELISA reflected spermatogenic activity without causing immune inflammatory responses. Orchitic mink showed excess antibody production accompanied by spermatogenic arrest, testicular leukocyte infiltration, and infertility. AIO serum labeled the postacrosomal region, the mid and end piece of mink sperm, whereas normal mink serum did not. Normal serum labeled plasma membranes, whereas AIO serum reacted with germ cell nuclei. Western blot analyses revealed that AIO serum reacted specifically to a 23- and 50-kDa protein. The number of apostain-labeled apoptotic cells was significantly higher in orchitic compared with normal tubules. However, apoptosis levels measured by ELISA in seminiferous tubular fractions (STf) were not significantly different in normal and orchitic tubules. The levels of CD36, TNF-α, TNF-α RI, IL-6, and Fas but not Fas-ligand (L), and ATP-binding cassette transporter ABCA1 were changed in AIO STf. TNF-α and IL-6 serum levels were increased during AIO. Fas localized to germ cells, Sertoli cells, and the lamina propria of the tubules and Fas-L, to germ cells. Fas colocalized with Fas-L in residual bodies in normal testis and in giant cells and infiltrating leukocytes in orchitic tubules.

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