scholarly journals Androgens and Postmeiotic Germ Cells Regulate Claudin-11 Expression in Rat Sertoli Cells

Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1532-1540 ◽  
Author(s):  
Anne Florin ◽  
Magali Maire ◽  
Aline Bozec ◽  
Ali Hellani ◽  
Sonia Chater ◽  
...  
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Inhibitory Effect ◽  
Positive Control ◽  
Maximum Effect ◽  
Dependent Manner ◽  
Adult Age ◽  
Adult Rat ◽  
Protein Levels ◽  
Negative Effect

In the present study we investigated whether fetal exposure to flutamide affected messenger and protein levels of claudin-11, a key Sertoli cell factor in the establishment of the hemotesticular barrier, at the time of two key events of postnatal testis development: 1) before puberty (postnatal d 14) during the establishment of the hemotesticular barrier, and 2) at the adult age (postnatal d 90) at the time of full spermatogenesis. The data obtained show that claudin-11 expression was inhibited in prepubertal rat testes exposed in utero to 2 and 10 mg/kg·d flutamide. However, in adult testes, the inhibition was observed only with 2, and not with 10, mg/kg·d of the antiandrogen. It is shown here that these differences between prepubertal and adult testes could be related to dual and opposed regulation of claudin-11 expression resulting from positive control by androgens and an inhibitory effect of postmeiotic germ cells. Indeed, testosterone is shown to stimulate claudin-11 expression in cultured Sertoli cells in a dose- and time-dependent manner (maximum effect with 0.06 μm after 72 h of treatment). In contrast, postmeiotic germ cells potentially exert a negative effect on claudin-11 expression, because adult rat testes depleted in spermatids (after local irradiation) displayed increased claudin-11 expression, whereas in a model of cocultured Sertoli and germ cells, spermatids, but not spermatocytes, inhibited claudin-11 expression. The apparent absence of claudin-11 expression changes in adult rat testes exposed to 10 mg/kg·d flutamide therefore could result from the antagonistic effects of 1) the inhibitory action of the antiandrogen and 2) the stimulatory effect of the apoptotic germ cells on claudin-11 expression. Together, due to the key role of claudin-11 in the hemotesticular barrier, the present findings suggest that such regulatory mechanisms may potentially affect this barrier (re)modeling during spermatogenesis.

Expression and localization of androgen receptor-interacting protein-4 in the testis

2007 ◽  
Vol 292 (2) ◽  
pp. E513-E522 ◽  
Author(s):  
Andrii Domanskyi ◽  
Fu-Ping Zhang ◽  
Mirja Nurmio ◽  
Jorma J. Palvimo ◽  
Jorma Toppari ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Sertoli Cell ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Hormone Receptor ◽  
Luteinizing Hormone Receptor ◽  
Dependent Manner ◽  
Cell Nuclei ◽  
Interacting Protein ◽  
Independent Functions

Androgen receptor-interacting protein 4 (ARIP4) belongs to the SNF2 family of proteins involved in chromatin remodeling, DNA excision repair, and homologous recombination. It is a DNA-dependent ATPase, binds to DNA and mononucleosomes, and interacts with androgen receptor (AR) and modulates AR-dependent transactivation. We have examined in this study the expression and cellular localization of ARIP4 during postnatal development of mouse testis. ARIP4 was detected by immunohistochemistry in Sertoli cell nuclei at all ages studied, starting on day 5, and exhibited the highest expression level in adult mice. At the onset of spermatogenesis, ARIP4 expression became evident in spermatogonia, pachytene, and diplotene spermatocytes. Immunoreactive ARIP4 antigen was present in Leydig cell nuclei. In Sertoli cells ARIP4 was expressed in a stage-dependent manner, with high expression levels at stages II–VI and VII–VIII. ARIP4 expression patterns did not differ significantly in testes of wild-type, follicle-stimulating hormone receptor knockout, and luteinizing hormone receptor knockout mice. In testes of hypogonadal mice, ARIP4 was found mainly in interstitial cells and exhibited lower expression in Sertoli and germ cells. In vitro stimulation of rat seminiferous tubule segments with testosterone, FSH, or forskolin did not significantly change stage-specific levels of ARIP4 mRNA. Heterozygous ARIP4+/− mice were haploinsufficient and had reduced levels of Sertoli-cell specific androgen-regulated Rhox5 (also called Pem) mRNA. Collectively, ARIP4 is an AR coregulator in Sertoli cells in vivo, but the expression in the germ cells implies that it has also AR-independent functions in spermatogenesis.

scholarly journals A novel Amh-Treck transgenic mouse line allows toxin-dependent loss of supporting cells in gonads

Reproduction ◽  
2014 ◽  
Vol 148 (6) ◽  
pp. H1-H9 ◽  
Author(s):  
Mai Shinomura ◽  
Kasane Kishi ◽  
Ayako Tomita ◽  
Miyuri Kawasumi ◽  
Hiromi Kanezashi ◽  
...  
Keyword(s):  
Germ Cells ◽  
Granulosa Cells ◽  
Sertoli Cells ◽  
Seminiferous Tubules ◽  
Specific Cell ◽  
Partial Recovery ◽  
Dependent Manner ◽  
Mouse Line ◽  
Cell Degeneration

Cell ablation technology is useful for studying specific cell lineages in a developing organ in vivo. Herein, we established a novel anti-Müllerian hormone (AMH)-toxin receptor-mediated cell knockout (Treck) mouse line, in which the diphtheria toxin (DT) receptor was specifically activated in Sertoli and granulosa cells in postnatal testes and ovaries respectively. In the postnatal testes of Amh-Treck transgenic (Tg) male mice, DT injection induced a specific loss of the Sertoli cells in a dose-dependent manner, as well as the specific degeneration of granulosa cells in the primary and secondary follicles caused by DT injection in Tg females. In the testes with depletion of Sertoli cell, germ cells appeared to survive for only several days after DT treatment and rapidly underwent cell degeneration, which led to the accumulation of a large amount of cell debris within the seminiferous tubules by day 10 after DT treatment. Transplantation of exogenous healthy Sertoli cells following DT treatment rescued the germ cell loss in the transplantation sites of the seminiferous epithelia, leading to a partial recovery of the spermatogenesis. These results provide not only in vivo evidence of the crucial role of Sertoli cells in the maintenance of germ cells, but also show that the Amh-Treck Tg line is a useful in vivo model of the function of the supporting cell lineage in developing mammalian gonads.

The inhibitory effect of celecoxib on mouse hepatoma H22 cell line on the arachidonic acid metabolic pathwayThis paper is one of a selection of papers published in this special issue entitled “Second International Symposium on Recent Advances in Basic, Clinical, and Social Medicine” and has undergone the Journal's usual peer review process.

2010 ◽  
Vol 88 (4) ◽  
pp. 603-609 ◽  
Author(s):  
Zhigang Xu ◽  
Ming Zhang ◽  
Xiaoyan Lv ◽  
Dan Xiang ◽  
Xuewen Zhang ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Peer Review Process ◽  
Inhibitory Effect ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Important Indicator ◽  
Protein Levels ◽  
Mouse Hepatoma ◽  
Cox 2 ◽  
Risk Of Cancer

Celecoxib is a selective inhibitor of cyclooxygenase-2 (COX-2). It may reduce the risk of cancer formation by affecting the metabolism of arachidonic acid (AA), which has been implicated in the development of cancer. Accordingly, this study was designed to determine the effects of celecoxib on the AA pathway in mouse hepatoma H22 cells. Celecoxib was found to inhibit the proliferation of H22 cells in a dose- and time-dependent manner. Low doses (50 and 100 µmol·L–1) of celecoxib caused an increase in the expression of cytosolic phospholipase A2 (cPLA2), but did not affect the expression of COX-2 in terms of the mRNA and protein levels. Surprisingly, the amount of AA was elevated and the level of prostaglandin E2 (PGE2) was unaltered in the culture supernatant. At higher celecoxib doses (200 and 400 µmol·L–1), the mRNA and protein of both COX-2 and cPLA2 were inhibited. The concentration of AA was increased, and PGE2 level was depressed in H22 cells. The ratio of AA to PGE2 was increased in a dose-dependent manner. Our findings suggest that the imbalance between AA and PGE2, characterized by increased AA at a low dosage and decreased PGE2 at a high dosage of celecoxib, was an important indicator of cytotoxicity of celecoxib on H22 cells.

scholarly journals Heat Treatment Induces Liver Receptor Homolog-1 Expression in Monkey and Rat Sertoli Cells

Endocrinology ◽  
2007 ◽  
Vol 148 (3) ◽  
pp. 1255-1265 ◽  
Author(s):  
Jian Guo ◽  
Shi-Xin Tao ◽  
Min Chen ◽  
Yu-Qiang Shi ◽  
Zhu-Qiang Zhang ◽  
...  
Keyword(s):  
Heat Treatment ◽  
Sertoli Cells ◽  
Dependent Manner ◽  
Positive Signal ◽  
Cytokeratin 18 ◽  
Adult Rat ◽  
Normal Monkey ◽  
Local Warming ◽  
Mature Spermatozoa

We demonstrated in this study that liver receptor homolog-1 (LRH-1) was expressed in the round spermatids in normal monkey testis, and no LRH-1 signal was observed in the Sertoli cells. After local warming (43 C) the monkey testis, however, LRH-1 expression was induced in the Sertoli cells in coincidence with activation of cytokeratin 18 (CK-18), a Sertoli cell dedifferentiated marker. Furthermore, we isolated rat primary Sertoli cells from testes at various stages of development and treated with 43 C water in vitro. The changes in LRH-1 as well as CK-18 expression were analyzed by confocal immunohistochemistry and Western blot. The results showed that LRH-1 was stage-dependently expressed in the Sertoli cells; no LRH-1-positive signal was detected in the cells obtained from the testes of adult rat on d 60 after birth when mature spermatozoa in the testis was completed. However, the mature Sertoli cells were warmed at the 43 C water bath for 15 min, and the LRH-1 signal was remarkably induced in a time-dependent manner, just like the changes of CK-18 expression in the Sertoli cells, suggesting that the heat-induced dedifferentiation of the mature Sertoli cells might be related to LRH-1 regulation. LRH-1 expression induced by the heat treatment was completely inhibited by the addition of ERK inhibitor U0126 in the culture, indicating that the heat-induced LRH-1 expression in the Sertoli cells may be regulated via ERK1/2 activation pathway. Testosterone was found to have no such effect on LRH-1 expression in the monkey and rat Sertoli cells.

scholarly journals Oleanolic Acid Induces Differentiation of Neural Stem Cells to Neurons: An Involvement of Transcription Factor Nkx-2.5

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
You Ning ◽  
Jianhua Huang ◽  
Bill Kalionis ◽  
Qin Bian ◽  
Jingcheng Dong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Neural Stem Cells ◽  
Oleanolic Acid ◽  
Maximum Effect ◽  
Regulatory Sequences ◽  
Specific Marker ◽  
Dependent Manner ◽  
Protein Levels ◽  
Pentacyclic Triterpenoid

Neural stem cells (NSCs) harbor the potential to differentiate into neurons, astrocytes, and oligodendrocytes under normal conditions and/or in response to tissue damage. NSCs open a new way of treatment of the injured central nervous system and neurodegenerative disorders. Thus far, few drugs have been developed for controlling NSC functions. Here, the effect as well as mechanism of oleanolic acid (OA), a pentacyclic triterpenoid, on NSC function was investigated. We found OA significantly inhibited neurosphere formation in a dose-dependent manner and achieved a maximum effect at 10 nM. OA also reduced 5-ethynyl-2′-deoxyuridine (EdU) incorporation into NSCs, which was indicative of inhibited NSC proliferation. Western blotting analysis revealed the protein levels of neuron-specific marker tubulin-βIII (TuJ1) and Mash1 were increased whilst the astrocyte-specific marker glial fibrillary acidic protein (GFAP) decreased. Immunofluorescence analysis showed OA significantly elevated the percentage of TuJ1-positive cells and reduced GFAP-positive cells. Using DNA microarray analysis, 183 genes were differentially regulated by OA. Through transcription factor binding site analyses of the upstream regulatory sequences of these genes, 87 genes were predicted to share a common motif for Nkx-2.5 binding. Finally, small interfering RNA (siRNA) methodology was used to silence Nkx-2.5 expression and found silence of Nkx-2.5 alone did not change the expression of TuJ-1 and the percentage of TuJ-1-positive cells. But in combination of OA treatment and silence of Nkx-2.5, most effects of OA on NSCs were abolished. These results indicated that OA is an effective inducer for NSCs differentiation into neurons at least partially by Nkx-2.5-dependent mechanism.

scholarly journals Formation of organotypic testicular organoids in microwell culture†

2019 ◽  
Vol 100 (6) ◽  
pp. 1648-1660 ◽  
Author(s):  
Sadman Sakib ◽  
Aya Uchida ◽  
Paula Valenzuela-Leon ◽  
Yang Yu ◽  
Hanna Valli-Pulaski ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Germ Cell ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Cell Interactions ◽  
Dependent Manner ◽  
Tissue Architecture ◽  
Cell Cell

Abstract Three-dimensional (3D) organoids can serve as an in vitro platform to study cell–cell interactions, tissue development, and toxicology. Development of organoids with tissue architecture similar to testis in vivo has remained a challenge. Here, we present a microwell aggregation approach to establish multicellular 3D testicular organoids from pig, mouse, macaque, and human. The organoids consist of germ cells, Sertoli cells, Leydig cells, and peritubular myoid cells forming a distinct seminiferous epithelium and interstitial compartment separated by a basement membrane. Sertoli cells in the organoids express tight junction proteins claudin 11 and occludin. Germ cells in organoids showed an attenuated response to retinoic acid compared to germ cells in 2D culture indicating that the tissue architecture of the organoid modulates response to retinoic acid similar to in vivo. Germ cells maintaining physiological cell–cell interactions in organoids also had lower levels of autophagy indicating lower levels of cellular stress. When organoids were treated with mono(2-ethylhexyl) phthalate (MEHP), levels of germ cell autophagy increased in a dose-dependent manner, indicating the utility of the organoids for toxicity screening. Ablation of primary cilia on testicular somatic cells inhibited the formation of organoids demonstrating an application to screen for factors affecting testicular morphogenesis. Organoids can be generated from cryopreserved testis cells and preserved by vitrification. Taken together, the testicular organoid system recapitulates the 3D organization of the mammalian testis and provides an in vitro platform for studying germ cell function, testicular development, and drug toxicity in a cellular context representative of the testis in vivo.

scholarly journals Insulin Deprivation Decreases Caspase-Dependent Apoptotic Signaling in Cultured Rat Sertoli Cells

ISRN Urology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
T. R. Dias ◽  
L. Rato ◽  
A. D. Martins ◽  
V. L. Simões ◽  
T. T. Jesus ◽  
...  
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Caspase 3 ◽  
Mrna Levels ◽  
Caspase 9 ◽  
Apoptotic Signaling ◽  
Protein Levels ◽  
Mrna And Protein Expression ◽  
Central Energy ◽  
Fertility Problems

Insulin is essential for the regulation of glucose homeostasis. Insulin dysfunction occurs in several pathologies, such as diabetes mellitus, which is associated with fertility problems. Somatic Sertoli cells (SCs) not only metabolize glucose to lactate, which is the central energy source used by developing germ cells, but also determine the germ cell population size. If a deregulation in SCs apoptosis occurs, it will affect germ cells, compromising spermatogenesis. As SCs apoptotic signaling is a hormonally regulated process, we hypothesized that the lack of insulin could lead to alterations in apoptotic signaling. Therefore, we examined the effect of insulin deprivation on several markers of apoptotic signaling in cultured rat SCs. We determined mRNA and protein expression of apoptotic markers as well as caspase-3 activity. SCs cultured in insulin deprivation demonstrated a significant decrease on mRNA levels of p53, Bax, caspase-9, and caspase-3 followed by a significant increase of Bax and decrease of caspase-9 protein levels relatively to the control. Caspase-3 activity was also decreased in SCs cultured in insulin deprivation conditions. Our results show that insulin deprivation decreases caspase-dependent apoptotic signaling in cultured rat SCs evidencing a possible mechanism by which lack of insulin can affect spermatogenesis and fertility.

Investigation of the potential role of the germ cell complement in control of the expression of transferrin mRNA in the prepubertal and adult rat testis

1997 ◽  
Vol 19 (1) ◽  
pp. 67-77 ◽  
Author(s):  
S M Maguire ◽  
M R Millar ◽  
R M Sharpe ◽  
J Gaughan ◽  
P T K Saunders
Keyword(s):  
Germ Cell ◽  
Mrna Expression ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Direct Access ◽  
Adult Rats ◽  
Rat Testis ◽  
Adult Rat

ABSTRACT Iron is required for the normal development of germ cells during spermatogenesis. Because these cells have no direct access to systemic iron, there exists a shuttle system involving production and secretion of the iron-transporting protein transferrin by the Sertoli cells. Previous reports using cultures of immature Sertoli cells exposed to adult germ cells, or in vivo studies involving germ cell-depleted adult rat testes, concluded that production of transferrin by Sertoli cells is modulated by germ cell complement. In the present study we have used in situ hybridisation with cRNA probes directed against the 5′ and 3′ ends of transferrin mRNA to examine the pattern of expression of transferrin in the immature and adult rat testis. Adult rats were treated with ethane dimethane sulphonate or methoxyacetic acid (MAA) to manipulate their testosterone levels or germ cell complement respectively. Initial findings obtained using the 3′ probe showed a decrease in transferrin mRNA associated with round spermatid depletion. However, these data were not confirmed by in situ hybridisation when the 5′ probe was used. The specificity of the probes was examined using Northern blotting and the 3′ probe was found to hybridise to the germ cell transcript for hemiferrin even under conditions of high stringency. Examination of immature and pubertal rat testes by in situ hybridisation using the 5′ transferrin-specific probe found that as early as 14 days of age the level of expression of transferrin mRNA was clearly different between tubules, and the mRNA appeared to be expressed in Leydig cells on and after day 31. In the adult rat testis, maximal expression of transferrin mRNA was found at stages VIII-XIV, calling into question the interpretation of the results of some previous studies showing expression of transferrin mRNA at all stages of the spermatogenic cycle. This stage-specific pattern of expression was not altered by acute germ cell depletion using MAA. However, Northern blot analysis showed a statistically significant increase in transferrin mRNA expression at 7 days after MAA treatment when pachytene spermatocytes were depleted from tubules at all stages of the spermatogenic cycle at which transferrin is normally expressed. In conclusion, we found that transferrin mRNA expression was not modulated by round spermatids as has been reported previously but that meiotic germ cells may influence expression of transferrin at specific stages of the spermatogenic cycle.

scholarly journals Effects of Sohamhyoong-Tang on Ovalbumin-Induced Allergic Reaction in BALB/c Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-9
Author(s):  
So Hyun Jo ◽  
Yun Jung Lee ◽  
Dae Gill Kang ◽  
Ho Sub Lee ◽  
Dae Ki Kim ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Allergic Diseases ◽  
Treated Group ◽  
Inhibitory Effect ◽  
Th2 Cells ◽  
Dependent Manner ◽  
Edema Formation ◽  
Protein Levels ◽  
Allergic Symptoms ◽  
Ige Mediated

IgE-mediated mast cell degranulation and excessive Th2 cells activation are major features of various allergic diseases.Sohamhyoong-tanghas been reported to have anti-inflammatory and antibacterial effects. In this study, we investigated the inhibitory effect ofSohamhyoong-tangextract (SHHTE) on allergic symptoms and inflammatory responses in ovalbumin- (OVA-) sensitized BALB/c mice. The mice were sensitized with OVA and alum at 2-week intervals and then orally given SHHTE for 13 days followed by intradermal OVA injection. Administration of SHHTE significantly reduced edema formation and inflammatory-cell infiltration in ear tissues. Total and OVA-specific IgEs as well as proinflammatory cytokine TNF-αand Th2-associated cytokine IL-4 levels were lower in the SHHTE-treated group than in the vehicle. SHHTE treatment significantly suppressed both mRNA and protein levels of IL-4 and IL-5 in OVA-stimulated splenocytes. SHHTE decreased Th1 (IFN-γ) and Th17 (IL-17a) cytokine mRNA expression but increased Treg cytokines (IL-10 and TGF-β1). Moreover, SHHTE significantly inhibited degranulation of RBL-2H3 cell line in a dose-dependent manner. Thus, SHHTE efficiently inhibited the allergic symptoms in an OVA-sensitized mouse model and its action may correlate with the suppression of IgE production by increasing IL-10 and TGF-β1, which can limit the function of other T helper cells and prevent the release of inflammatory mediators from mast cells. These results suggest that SHHTE could be a therapeutic agent for treating various allergic diseases.

Inhibition of aromatase activity in rat Sertoli cells by thyroid hormone

1994 ◽  
Vol 140 (3) ◽  
pp. 431-436 ◽  
Author(s):  
S Ulisse ◽  
E A Jannini ◽  
E Carosa ◽  
D Piersanti ◽  
F M Graziano ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Cyclic Amp ◽  
Sertoli Cells ◽  
Inhibitory Effect ◽  
Aromatase Activity ◽  
Dependent Manner ◽  
Maximal Dose ◽  
Cyclic Amp Accumulation ◽  
Order Of Magnitude ◽  
Dose Dependent

Abstract Basal and FSH-induced aromatase activity in prepubertal rat Sertoli cells was inhibited by l-tri-iodothyronine (T3) in a time- and dose-dependent manner. The effect was evident only after 6 h of preincubation with T3 (10−7 m) and the half-maximal dose was 0·5 ±0·2 nm, which correlated with the Kd of the nuclear T3 receptor of rat Sertoli cells (Kd=1–2 nm). The effect was specific as judged by the lack of effect of the T3 analogue 3-iodo-l-thyrosine. The inhibitory effect of T3 was present over the entire range of FSH concentrations used (0·001–100 ng/ml). In T3-treated Sertoli cells, aromatase activity induced by 8-bromo-cyclic AMP was inhibited by the same order of magnitude as that of FSH, thus suggesting that the inhibitory effect of T3 was downstream from cyclic AMP formation. Furthermore, pretreatment of Sertoli cells cultures with T3 (24 h, 10−7 m) did not affect basal or FSH-induced extracellular cyclic AMP accumulation. This effect of T3 on rat Sertoli cell aromatase activity may be regarded as a part of the integrated mechanism by which thyroid hormone modulates the functions of the seminiferous epithelium. Journal of Endocrinology (1994) 140, 431–436

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