Prepubertal male rats with high rates of germ-cell apoptosis present exacerbated rates of germ-cell apoptosis after serotonin depletion

2016 ◽  
Vol 28 (6) ◽  
pp. 806 ◽  
Author(s):  
Néstor Méndez Palacios ◽  
María Elena Ayala Escobar ◽  
Maximino Méndez Mendoza ◽  
Rubén Huerta Crispín ◽  
Octavio Guerrero Andrade ◽  
...  
Keyword(s):  
Gene Expression ◽  
Germ Cell ◽  
Mrna Expression ◽  
Cell Apoptosis ◽  
Differential Sensitivity ◽  
Male Rats ◽  
Mrna Levels ◽  
Germ Cell Apoptosis ◽  
Expression Of Genes ◽  
Prepubertal Rats

Male germ-cell apoptosis occurs naturally and can be increased by exposure to drugs and toxic chemicals. Individuals may have different rates of apoptosis and are likely to also exhibit differential sensitivity to outside influences. Previously, we reported that p-chloroamphetamine (pCA), a substance that inhibits serotonin synthesis, induced germ-cell apoptosis in prepubertal male rats. Here, we identified prepubertal rats with naturally high or low rates of germ-cell apoptosis and evaluated gene expression in both groups. Bax and Shbg mRNA levels were higher in rats with high rates of germ-cell apoptosis. Rats were then treated with pCA and the neuro-hormonal response and gene expression were evaluated. Treatment with pCA induced a reduction in serotonin concentrations but levels of sex hormones and gonadotrophins were not changed. Rats with initially high rates of germ-cell apoptosis had even higher rates of germ-cell apoptosis after treatment with pCA. In rats with high rates of germ-cell apoptosis Bax mRNA expression remained high after treatment with pCA. On the basis of category, an inverse relationship between mRNA expression of Bax and Bcl2, Bax and AR and Bax and Hsd3b2 was found. Here we provide evidence that innate levels of germ-cell apoptosis could be explained by the level of mRNA expression of genes involved with apoptosis and spermatogenesis.

scholarly journals The Thioredoxin System is Regulated by the ASK-1/JNK/p38/Survivin Pathway During Germ Cell Apoptosis

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3333 ◽  
Author(s):  
Al-Kandari ◽  
Fadel ◽  
Al-Saleh ◽  
Khashab ◽  
Al-Maghrebi
Keyword(s):  
Germ Cell ◽  
Mrna Expression ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Specific Inhibitor ◽  
Apoptosis Pathway ◽  
Germ Cell Apoptosis ◽  
Thioredoxin System

The aim is to explore the mechanism of the apoptosis signal-regulating kinase-1 (ASK-1) signaling pathway and the involvement of the thioredoxin (Trx) system during testicular ischemia reperfusion injury (tIRI) by using ASK-1 specific inhibitor, NQDI-1. Male Sprague-Dawley rats (n = 36, 250–300 g) were equally divided into 3 groups: sham, tIRI, and tIRI + NQDI-1 (10 mg/kg, i.p, pre-reperfusion). For tIRI induction, the testicular cord and artery were occluded for 1 h followed by 4 h of reperfusion. Histological analyses, protein immunoexpression, biochemical assays, and real-time PCR were used to evaluate spermatogenesis, ASK-1/Trx axis expression, enzyme activities, and relative mRNA expression, respectively. During tIRI, ipsilateral testes underwent oxidative stress indicated by low levels of superoxide dismutase (SOD) and Glutathione (GSH), increased oxidative damage to lipids and DNA, and spermatogenic damage. This was associated with induced mRNA expression of pro-apoptosis genes, downregulation of antiapoptosis genes, increased caspase 3 activity and activation of the ASK-1/JNK/p38/survivin apoptosis pathway. In parallel, the expression of Trx, Trx reductase were significantly reduced, while the expression of Trx interacting protein (TXNIP) and the NADP+/ nicotinamide Adenine Dinucleotide phosphate (NADPH) ratio were increased. These modulations were attenuated by NQDI-1 treatment. In conclusion, the Trx system is regulated by the ASK-1/Trx/TXNIP axis to maintain cellular redox homeostasis and is linked to tIRI-induced germ cell apoptosis via the ASK-1/JNK/p38/survivin apoptosis pathway.

Tumor VEGFA gene expression is associated with serum lactate dehydrogenase (LDH) levels and intratumoral mRNA expression of genes involved in glycolysis in patients with metastatic colorectal cancer (mCRC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3530-3530 ◽  
Author(s):  
M. Azuma ◽  
M. M. Shi ◽  
C. J. Jacques ◽  
C. Barrett ◽  
K. D. Danenberg ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Lactate Dehydrogenase ◽  
Metastatic Colorectal Cancer ◽  
Mrna Expression ◽  
High Serum ◽  
Serum Lactate Dehydrogenase ◽  
Mrna Levels ◽  
Glut 1 ◽  
Expression Of Genes

3530 Background: It is well known that angiogenesis and glycolysis are regulated by hypoxic conditions. Recent clinical trials (CONFIRM1 and CONFIRM2) have shown that patients with mCRC with high serum LDH benefited from PTK787/ZK 222584, a VEGF receptor tyrosine kinase inhibitor. We tested the hypothesis that patients with high serum LDH have increased intratumoral expression of genes involved with hypoxia (hypoxia inducible factor (HIF1a and 2a) and lactate dehydrogenase A (LDHA) and glycolysis (glucose transporter 1 (Glut-1) and genes involved in angiogenesis such as vascular endothelial growth factor A (VEGFA) and neuropilin 1 (NRP1) in patients with mCRC. Methods: 78 formalin fixed paraffin embedded (FFPE) tumor samples from 36 patients (20 males, 16 females: Median age 59 years (range 29–84) with mCRC who underwent first line therapy (not from CONFIRM trials) were analyzed. In addition, tumor gene expression was correlated with serum LDH levels from the same group of patients. FFPE tissues were dissected using laser-captured microdissection and analyzed LDHA, VEGFA, HIF1a, HIF2a, Glut-1 and NRP1 mRNA expression using a quantitative real-time RT-PCR method. Gene expression values (relative mRNA levels) are expressed as ratios between the target gene and internal reference gene (beta-actin). Results: Spearman Rank Correlation Analysis of Associations Between serum LDH levels and Gene Expression values. Conclusions: Our results demonstrate that intratumoral gene expression of LDHA, HIF1a and HIF2a, Glut-1 and VEGFA are significantly correlated. Patients with high serum LDH have increased intratumoral gene expression of VEGFA. These results support the hypothesis that serum LDH levels may serve as a surrogate marker for activation of the HIF related genes in the tumor. These observations may explain the efficacy of PTK787 in metastatic colorectal cancer patients with high serum LDH levels. [Table: see text] [Table: see text]

Sexual dimorphism of hepatic 11β-hydroxysteroid dehydrogenase in the rat: the role of growth hormone patterns

1994 ◽  
Vol 143 (3) ◽  
pp. 541-548 ◽  
Author(s):  
S C Low ◽  
K E Chapman ◽  
C R W Edwards ◽  
T Wells ◽  
I C A F Robinson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sexual Dimorphism ◽  
Mrna Expression ◽  
Hydroxysteroid Dehydrogenase ◽  
Male Rats ◽  
Total Daily Dose ◽  
Mrna Levels ◽  
Control Female ◽  
Gh Secretion ◽  
Repressive Effect

Abstract 11 β-Hydroxysteroid dehydrogenase (11β-HSD) catalyses the reversible metabolism of corticosterone to inert 11-dehydrocorticosterone. At least two isoforms exist. 11β-HSD-1, the first to be characterised and the only isoform for which a cDNA has been isolated, is highly expressed in liver, kidney and hippocampus. The activity of 11β-HSD in rat liver is higher in males, due to oestrogen repression of 11β-HSD-1 gene transcription in females. Sexual dimorphism in rodent liver proteins is frequently mediated indirectly via sex-specific patterns of GH release (continuous in females, pulsatile in males). We have now investigated whether this applies to 11β-HSD, using dwarf rats (congenitally deficient in GH) and hypophysectomised animals. 11β-HSD activity and 11β-HSD-1 mRNA expression in liver was significantly lower in control female than male rats (50% and 72% of male levels respectively). These sex differences in the liver were attenuated in dwarf rats, with both males and females showing similar levels of 11 β-HSD activity to control males. Administration of continuous (female pattern) GH to dwarf male rats decreased hepatic 11β-HSD activity (30% fall) and mRNA expression (77% fall), whereas the same total daily dose of GH given in the male (pulsatile) pattern had no effect on hepatic 11 β-HSD in female dwarf rats. Continuous GH also attenuated hepatic 11 β-HSD activity (25% fall) and 11β-HSD-1 mRNA expression (82% fall) in hypophysectomised animals. However, oestradiol itself suppressed hepatic 11β-HSD activity (25% fall) and 11β-HSD-1 mRNA expression (60% fall) in hypophysectomised rats. Renal 11 β-HSD activity showed no sexual dimorphism in control or dwarf rats, although overall activity was lower in dwarf animals. By contrast, 11β-HSD-1 mRNA expression was higher in male than female kidney in both control and dwarf strains. Neither GH pattern had any effect on 11β-HSD activity or 11β-HSD-1 mRNA levels in the kidney of dwarf rats, although continuous GH attenuated 11β-HSD activity (28% fall) and 11β-HSD-1 mRNA expression in kidney (47% decrease) in hypophysectomised animals. Oestradiol attenuated renal 11β-HSD-1 mRNA expression (74% fall) in hypophysectomised rats, but increased enzyme activity (62% rise) in the kidney. None of the manipulations had any effect on hippocampal 11 β-HSD activity or gene expression. These data demonstrate the following. (i) Sexual dimorphism of hepatic 11β-HSD is mediated, in part, via sex-specific patterns of GH secretion acting on 11β-HSD-1 gene expression. (ii) There is an additional direct repressive effect of oestrogen on hepatic 11β-HSD-1. (iii) Other tissue-specific factors are involved in regulating 11β-HSD-1, as neither peripheral GH nor oestrogen have effects upon hippocampal 11β-HSD-1. (iv) The regulation of 11β-HSD-1 mRNA expression in the kidney broadly parallels the liver. The lack of correlation between changes in expression of the 11β-HSD-1 gene and renal 11β-HSD activity reflects the presence of an additional gene product(s) in the kidney, the expression of which is largely independent of GH. Journal of Endocrinology (1994) 143, 541–548

scholarly journals Effects of Exposure to Bisphenol A during Pregnancy on the Pup Testis Function

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Qingtao Yang ◽  
Xuxia Sui ◽  
Junjun Cao ◽  
Caixia Liu ◽  
Shukai Zheng ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Germ Cell ◽  
Cell Apoptosis ◽  
Mrna Level ◽  
Regulatory Protein ◽  
Seminiferous Tubules ◽  
Mrna Levels ◽  
Germ Cell Apoptosis ◽  
Testosterone Levels ◽  
Steroidogenic Acute Regulatory

Testosterone plays an important prenatal role in male testis development. Bisphenol A (BPA) exposure during pregnancy affects testosterone levels and germ cell apoptosis of male pups, but little information is available for the mechanism. The aim of the present study was to investigate the mechanism by which BPA alters testosterone levels and germ cell apoptosis. Pregnant female C57BL/6J mice, throughout gestation, had access to drinking water containing BPA at 5 and 50 μg/mL. Male pups were euthanized on postnatal days (PNDs) 1, 14, and 35. Relative to control, BPA exposure at 5 and 50 μg/ml decreased testosterone level, as measured by chemiluminescent immunoassay, on PND14. Real-time PCR indicated mRNA levels for steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (CYP11A1), and 3-β-hydroxysteroid dehydrogenase/△-5-4 isomerase (3β-HSD) were significantly lower in the BPA pups compared to control. Additionally, BPA increased the percentage of TUNEL-positive seminiferous tubules, decreased the mRNA level of Bcl-2, and increased Bax expression, indicative of increased apoptosis. These results suggest that BPA exposure in utero decreases the testosterone concentration by decreasing steroidogenic enzymes (StAR, CYP11A1, and 3β-HSD). Furthermore, BPA exposure increases the apoptosis of germ cells, which is associated with proapoptotic changes in the levels of Bcl-2 and Bax.

scholarly journals Adult-only exposure of male rats to a diet of high phytoestrogen content increases apoptosis of meiotic and post-meiotic germ cells

Reproduction ◽  
2007 ◽  
Vol 133 (1) ◽  
pp. 11-19 ◽  
Author(s):  
Stephen Assinder ◽  
Ryan Davis ◽  
Mark Fenwick ◽  
Amy Glover
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Cell Apoptosis ◽  
Critical Role ◽  
Male Rats ◽  
Male Rat ◽  
Sperm Production ◽  
Germ Cell Apoptosis ◽  
Sperm Counts ◽  
Male Wistar Rats

Apoptosis plays a critical role in regulating sperm production. Removal of androgens and gonadotropins, or estrogen administration induces germ cell apoptosis. It is hypothesized that dietary phytoestrogens increase apoptosis of developing germ cells, decreasing sperm production. This study aimed to test this in rats fed a high phytoestrogen diet only during adulthood. Male Wistar rats used in this study were offspring of females maintained on a low phytoestrogen diet prior to conception through to weaning. After weaning, juveniles were fed the same low phytoestrogen diet into adulthood. A cohort of males were transferred to a high phytoestrogen diet for 24 days and subsequently testes were collected from all animals. In the high phytoestrogen fed group, homogenization-resistant sperm counts were significantly decreased, as were epididymal sperm counts. Morphometric analysis determined round and elongated spermatid volumes to be significantly decreased, but seminiferous tubule lumen diameters to be significantly increased. TUNEL analysis determined that apoptosis of spermatocytes and round spermatids was significantly greater in the high phytoestrogen fed rats. Neither plasma gonadotropin concentrations nor testicular testosterone were altered. In conclusion, exposure of the adult male rat to a high phytoestrogen diet disrupts spermatogenesis, increasing germ cell apoptosis. This effect is independent of the hypothalamo–pituitary–testicular axis and is likely due to disruption of estrogen’s actions in the testis.

Bcl-2 and Bax are involved in experimental cryptorchidism-induced testicular germ cell apoptosis in rhesus monkey

Contraception ◽  
2003 ◽  
Vol 68 (4) ◽  
pp. 297-301 ◽  
Author(s):  
Zhi-Hong Zhang ◽  
Xuan Jin ◽  
Xue-Sen Zhang ◽  
Zhao-Yuan Hu ◽  
Ru-Jin Zou ◽  
...  
Keyword(s):  
Rhesus Monkey ◽  
Germ Cell ◽  
Cell Apoptosis ◽  
Testicular Germ Cell ◽  
Germ Cell Apoptosis

scholarly journals TheCaenorhabditis elegans ing-3Gene Regulates Ionizing Radiation-Induced Germ-Cell Apoptosis in a p53-Associated Pathway

Genetics ◽  
2008 ◽  
Vol 181 (2) ◽  
pp. 473-482 ◽  
Author(s):  
Jingjing Luo ◽  
Sitar Shah ◽  
Karl Riabowol ◽  
Paul E. Mains
Keyword(s):  
Ionizing Radiation ◽  
Germ Cell ◽  
Cell Apoptosis ◽  
Germ Cell Apoptosis ◽  
Radiation Induced
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