scholarly journals Leydig cell apoptosis in the rat testes after administration of the cytotoxin ethane dimethanesulphonate: role of the Bcl-2 family members

1998 ◽  
Vol 157 (2) ◽  
pp. 317-326 ◽  
Author(s):  
MF Taylor ◽  
I Woolveridge ◽  
AD Metcalfe ◽  
CH Streuli ◽  
JA Hickman ◽  
...  
Keyword(s):  
Cell Death ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Family Members ◽  
Tumour Suppressor Gene ◽  
Male Rats ◽  
Seminiferous Tubules ◽  
Gene Products ◽  
Bax Protein ◽  
Ethane Dimethanesulphonate

Ethane dimethanesulphonate (EDS) is cytotoxic to Leydig cells in the adult rat. To investigate the role and regulation of apoptosis in the Leydig cell, EDS (100 mg/kg i.p.) was administered to adult male rats and the testes examined 6, 12, 18, 24, 48 and 72 h later. Numbers of Leydig cells, identified by 3 beta-hydroxysteroid dehydrogenase immuno-histochemistry started to fall by 12 h after EDS injection and were almost undetectable by 72 h. Apoptotic cells in the interstitium, visualised by in situ end labelling of DNA, increased in number to reach a maximum 24 h after injection of EDS, and were undetectable by 72 h. In many tissues the apoptosis-related gene products act in cohort: Bcl-2 and Bcl-xl promoting survival of a cell, whilst Bax promotes cell death often positively regulated by the tumour-suppressor gene p53. Western blot analysis showed that: (1) Bcl-2 and p53 were absent from interstitial Leydig cells but were expressed in the seminiferous tubules. (2) Bax protein although expressed in the interstitium was not present in the Leydig cells. (3) Bcl-xl in Leydig cells was transiently increased after EDS. In conclusion, EDS kills Leydig cells by apoptosis; however the control of Leydig cell death does not involve p53 or the Bcl-2 family members but may require other gene products yet to be identified.

Effects of recombinant human FSH in immature hypophysectomized male rats: evidence for Leydig cell-mediated action on spermatogenesis

1994 ◽  
Vol 141 (3) ◽  
pp. 449-457 ◽  
Author(s):  
T Matikainen ◽  
J Toppari ◽  
K K Vihko ◽  
I Huhtaniemi
Keyword(s):  
Leydig Cell ◽  
Leydig Cells ◽  
Cell Function ◽  
Serum Testosterone ◽  
Male Rats ◽  
Seminiferous Tubules ◽  
Spermatogenic Cells ◽  
Hypophysectomized Rats ◽  
First Time ◽  
Recombinant Human Fsh

Abstract The mode of FSH actions within the testis was studied in immature hypophysectomized male rats by treatment with recombinant human FSH (recFSH, Org 32489). To elucidate the involvement of Leydig cells and androgens in the maintenance of spermatogenesis in FSH-treated hypophysectomized rats further, the recFSH treatment was given both alone and after destruction of Leydig cells with ethane-1,2-dimethane sulphonate (EDS). Three days after hypophysectomy (at 31 days of age) the rats were given one i.p. injection of vehicle or EDS and, 4 days later, they were implanted with osmotic minipumps releasing either 0·9% (w/v) NaCl or 1 IU recFSH/day. Recombinant FSH alone increased testicular weights 2·5-fold in 7 days (P<0·01). The effect of FSH was similar in EDS-pretreated rats (P<0·01). Testicular testosterone increased from 6·5 ± 1·6 to 16·9 ± 5·3 (s.e.m.) pmol/g tissue (P<0·05) and serum testosterone from 0·12 ± 0·02 to 0·22 ± 0·03 nmol/l (P<0·05) when the rats were treated with recFSH. EDS alone did not affect testicular testosterone but, when combined with recFSH, it totally abolished the stimulatory effect of FSH on testosterone. Testicular binding of 125I-labelled iodo human chorionic gonadotrophin (hCG) and 125I-labelled iodo recFSH was increased 2·5- and 2·1-fold respectively with recFSH treatment (P<0·01). EDS, either alone or with FSH, abolished specific testicular hCG binding (P<0·01), but had no effect on that of recFSH. However, FSH increased its own receptors only in animals not treated with EDS. Histological analysis of the testes revealed that the diameters of the seminiferous tubules increased from 115 ± 6·1 to 160 ± 7·2 μm (P<0·05) with recFSH, and a comparable increase was observed when EDS treatment preceded that of recFSH (143 ± 1·5 μm, P<0·05 vs. controls). Quantification of the spermatogenic cells indicated that recFSH supported the progression of spermatogenesis, as shown by increased number of meiotic and haploid spermatogenic cells (P<0·05). In all EDS-treated animals, spermatogenesis was severely disturbed and only a few spermatids were seen. In conclusion: (1) these results further support the suggestion that FSH has indirect stimulatory effects on Leydig cell function, (2) the completion of meiosis and spermiogenesis are supported by FSH, the effect of which is enhanced by the presence of Leydig cells, suggesting its dependence on androgens, and (3) we show for the first time that FSH is able to stimulate its own receptors only in the presence of Leydig cell-derived factors, probably androgens. Journal of Endocrinology (1994) 141, 449–457

Inhibition of testicular and somatic development after treatment of the postnatal rat with the Leydig cell cytotoxic ethylene dimethanesulphonate

1988 ◽  
Vol 119 (3) ◽  
pp. 467-NP ◽  
Author(s):  
I. D. Morris ◽  
R. G. Lendon ◽  
A. Zaidi
Keyword(s):  
Leydig Cell ◽  
Leydig Cells ◽  
Serum Testosterone ◽  
Male Rats ◽  
Seminiferous Tubules ◽  
Testicular Development ◽  
Interstitial Tissue ◽  
Somatic Development ◽  
Serum Lh ◽  
Loss Of Weight

ABSTRACT The Leydig cell cytotoxic ethylene dimethanesulphonate (EDS) was administered s.c. daily (50 mg/kg) to male rats aged 5–16 days. Apart from loss of weight and that the eyelids unfused earlier, no gross toxicity was observed during treatment. On day 17 testis weights, serum testosterone concentrations, testicular serum testosterone content and 125I-labelled human chorionic gonadotrophin (hCG) binding to testicular homogenates were reduced. Serum LH and FSH concentrations were elevated. The testes did not recover from EDS treatment and at 63 and 120 days were minute (<2% of control), and the prostate and seminal vesicles were small although not completely atrophied. In addition, body weights were substantially reduced. Serum and testicular testosterone and 125I-labelled hCG binding to testicular homogenates were reduced but not absent. Serum LH and FSH concentrations were increased. Light microscopy of the adult testes showed that EDS treatment inhibited the development of the seminiferous tubules. Most of the tubules were devoid of germ cells and Sertoli cells were rare. Occasionally tubules also contained spermatogonia and spermatocytes but no signs of spermiogenesis. The testes were composed mainly of closely packed interstitial tissue with no lymphatic space. The interstitial cells resembled Leydig cells and stained for 3β-hydroxysteroid dehydrogenase. Histochemically identified Leydig cells were absent during treatment but reappeared when treatment was withdrawn. Testicular Leydig cell numbers were only 7% of control values in the 63-day-old EDS-treated rat. The effect on the testis of EDS treatment administered at a crucial time of testicular development may be explained by withdrawal of androgen; however, the systemic effects indicate non-specific toxicity so any explanation of these changes must be viewed with caution. J. Endocr. (1988) 119, 467–474

A switch in the cellular localization of macrophage migration inhibitory factor in the rat testis after ethane dimethane sulfonate treatment

1999 ◽  
Vol 112 (9) ◽  
pp. 1337-1344
Author(s):  
A. Meinhardt ◽  
M. Bacher ◽  
M.K. O'Bryan ◽  
J.R. McFarlane ◽  
C. Mallidis ◽  
...  
Keyword(s):  
Western Blot ◽  
Leydig Cell ◽  
Migration Inhibitory Factor ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Macrophage Migration Inhibitory Factor ◽  
Inhibitory Factor ◽  
Male Rats ◽  
Seminiferous Tubules ◽  
Macrophage Migration

Macrophage migration inhibitory factor (MIF), one of the first cytokines to be discovered, has recently been localized to the Leydig cells in adult rat testes. In the following study, the response of MIF to Leydig cell ablation by the Leydig cell-specific toxin ethane dimethane sulfonate (EDS) was examined in adult male rats. Testicular MIF mRNA and protein in testicular interstitial fluid measured by ELISA and western blot were only marginally reduced by EDS treatment, in spite of the fact that the Leydig cells were completely destroyed within 7 days. Immunohistochemistry using an affinity-purified anti-mouse MIF antibody localized MIF exclusively to the Leydig cells in control testes. At 7 days post-EDS treatment, there were no MIF immunopositive Leydig cells in the interstitium, although distinct MIF immunostaining was observed in the seminiferous tubules, principally in Sertoli cells and residual cytoplasm, and some spermatogonia. A few peritubular and perivascular cells were also labelled at this time, which possibly represented mesenchymal Leydig cell precursors. At 14 and 21 days, Sertoli cell MIF immunoreactivity was observed in only a few tubule cross-sections, while some peritubular and perivascular mesenchymal cells and the re-populating immature Leydig cells were intensely labeled. At 28 days after EDS-treatment, the MIF immunostaining pattern was identical to that of untreated and control testes. The switch in the compartmentalization of MIF protein at 7 days after EDS-treatment was confirmed by western blot analysis of interstitial tissue and seminiferous tubules separated by mechanical dissection. These data establish that Leydig cell-depleted testes continue to produce MIF, and suggest the existence of a mechanism of compensatory cytokine production involving the Sertoli cells. This represents the first demonstration of a hitherto unsuspected pattern of cellular interaction between the Leydig cells and the seminiferous tubules which is consistent with an essential role for MIF in male testicular function.

scholarly journals Quantitation of Leydig Cell in Testicular Biopsies of Gossypol Treated rats

2005 ◽  
Vol 29 (1) ◽  
pp. 179-189
Author(s):  
Muhannad A. A. Al Bayaty
Keyword(s):  
Cell Density ◽  
Leydig Cell ◽  
Seminiferous Tubule ◽  
Leydig Cells ◽  
Histological Section ◽  
Treated Group ◽  
Male Rats ◽  
Male Rat ◽  
Seminiferous Tubules ◽  
Cell Clusters

Leydig cell density was evaluated quantitatively in bilateral testicularbiopsies from twenty male rats of two equal groups Gossypol treated andcontrol. The method utilized for this quantitation is based on the determinationof total number of Leydig cells, Leydig cell clusters and seminiferous tubules inthe entire histological section of each biopsy and the calculation of the followingindices: mean Leydig cells per seminiferous tubule, mean Leydig cell clustersper seminiferous tubule and mean Leydig cells per cluster. A significant positivecorrelation between Leydig cells per tubule and Leydig cell clusters per tubulewas demonstrated. The results of indices curve showed shifted all the curves tothe right in Gossypol treated group, a significant reduction in plasmatestosterone levels of Gossypol treatment group as compared to control groupwhich is due to decrease in Leydig cells number, suggesting that determinationof Leydig cell clusters per seminiferous tubule in testicular biopsies is anobjective and clinically applicable method for quantitative evaluation of Leydigcell density and indirectly evaluated the secretary activity of the testicularLeydig cells. The results are attributed to the direct effect of Gossypol onsecretary site of testosterone in Leydig cells or presumably indirect disturbanceof hypothalamic – pituitary gland – Leydig cells axis. An Association ofGossypol treatment with Leydig cell hypo-function and decrease number of cellswas noticed for the male rat testosterone level. To our knowledge this is the firstreport of quantitative analysis of Leydig cell density in rat with Gossypoltreatment and it is suitable for clinical evaluation of testicular dysfunction.التأثر

scholarly journals Influence of long-term dietary administration of procymidone, a fungicide with anti-androgenic effects, or the phytoestrogen genistein to rats on the pituitary–gonadal axis and Leydig cell steroidogenesis

2005 ◽  
Vol 187 (1) ◽  
pp. 117-124 ◽  
Author(s):  
K Svechnikov ◽  
V Supornsilchai ◽  
M-L Strand ◽  
A Wahlgren ◽  
D Seidlova-Wuttke ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Serum Level ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Ex Vivo ◽  
Elevated Serum ◽  
Seminiferous Tubules ◽  
Dibutyryl Camp

Procymidone is a fungicide with anti-androgenic properties, widely used to protect fruits from fungal infection. Thereby it contaminates fruit products prepared for human consumption. Genistein-containing soy products are increasingly used as food additives with health-promoting properties. Therefore we examined the effects of long-term dietary administration (3 months) of the anti-androgen procymidone (26.4 mg/animal per day) or the phytoestrogen genistein (21.1 mg/animal per day) to rats on the pituitary-gonadal axis in vivo, as well as on Leydig cell steroidogenesis and on spermatogenesis ex vivo. The procymidone-containing diet elevated serum levels of LH and testosterone and, furthermore, Leydig cells isolated from procymidone-treated animals displayed an enhanced capacity for producing testosterone in response to stimulation by hCG or dibutyryl cAMP, as well as elevated expression of steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage (P450 scc) and cytochrome P450 17α (P450c17). In contrast, the rate of DNA synthesis during stages VIII and IX of spermatogenesis in segments of seminiferous tubules isolated from genistein-treated rats was decreased without accompanying changes in the serum level of either LH or testosterone. Nonetheless, genistein did suppress the ex vivo steroidogenic response of Leydig cells to hCG or dibutyryl cAMP by down-regulating their expression of P450 scc. Considered together, our present findings demonstrate that long-term dietary administration of procymidone or genistein to rats exerts different effects on the pituitary–gonadal axis in vivo and on Leydig cell steroidogenesis ex vivo. Possibly as a result of disruption of hormonal feedback control due to its anti-androgenic action, procymidone activates this endocrine axis, thereby causing hyper-gonadotropic activation of testicular steroidogenesis. In contrast, genistein influences spermatogenesis and significantly inhibits Leydig cell steroidogenesis ex vivo without altering the serum level of either LH or testosterone.

TESTICULAR HISTO-MORPHOLOGY OF YOUNG RATS TREATED WITH OESTRADIOL-17β BENZOATE

1964 ◽  
Vol 46 (1) ◽  
pp. 25-30 ◽  
Author(s):  
Manuel Maqueo ◽  
Fred A. Kind
Keyword(s):  
Leydig Cells ◽  
Post Treatment ◽  
Seminiferous Epithelium ◽  
Male Rats ◽  
Seminiferous Tubules ◽  
Pathological Changes ◽  
Testicular Damage ◽  
Oestrogen Treatment ◽  
Histological Studies ◽  
Oestradiol Benzoate

ABSTRACT Oestradiol-17β benzoate, 120 βg, injected into five-day old male rats inhibited maturation of the seminiferous epithelium as demonstrated by histological studies performed 40–55 days post-treatment. The oestrogen treatment was ineffective when administered at the age of 20 days. The degree of testicular damage appeared to be correlated with the amount of steroid used. A dose of 240 μg of oestradiol benzoate led to severe pathological changes in almost 100 per cent of the seminiferous tubules and atrophy of the Leydig cells.

Interstitial fluid volume in the rat testis: androgen-dependent regulation by the seminiferous tubules?

1989 ◽  
Vol 120 (2) ◽  
pp. 215-NP ◽  
Author(s):  
S. Maddocks ◽  
R. M. Sharpe
Keyword(s):  
Leydig Cells ◽  
Interstitial Fluid ◽  
Single Injection ◽  
Fluid Volume ◽  
Male Rats ◽  
Seminiferous Tubules ◽  
Rat Testis ◽  
Adult Rat ◽  
Interstitial Fluid Volume ◽  
Dependent Mechanism

ABSTRACT Regulation of testicular interstitial fluid (IF) volume has been investigated in adult male rats in which the Leydig cells were selectively destroyed with a single i.p. injection of ethane dimethane sulphonate (EDS). Following this treatment, some animals also received testosterone supplementation by s.c. injection every 3 days, beginning either from the time of EDS injection, or 3–12 days afterwards. The volume of IF obtained by drip collection was determined, and testosterone and gonadotrophin concentrations measured in blood and in IF. Testosterone levels in IF and serum became undetectable by 3 days after EDS treatment. IF volume was reduced by 50% (P < 0·01) to reach a minimum level between 6 and 9 days after treatment. However, this decline was prevented in the absence of Leydig cells by supplementation with testosterone from the time of EDS injection, a treatment which also kept gonadotrophins at minimum or undetectable levels. Furthermore, the reduced IF volume seen up to 9 days after treatment with EDS alone could be restored to control levels within 3 days by a single injection of testosterone. The results obtained demonstrate that androgens, but not Leydig cells or gonadotrophins, are required for the maintenance of interstitial fluid volume in the adult rat testis. It is suggested that the seminiferous tubules may mediate this response, through an androgen-dependent mechanism. Journal of Endocrinology (1989) 120, 215–222

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