ABSTRACT
The aim of this study was to investigate the effects of maternal exposure to di-( n-butyl) phthalate (DBP) on testicular development and function in pre-pubertal and post-pubertal male rat offspring. Fourteen pregnant female rats were equally divided into two groups: a control group and a DBP-treated group. During gestation day (GD) 12 to postnatal day (PND) 14, the control group was administered 1 ml/day corn oil, and the DBP-treated group was administered DBP 500 mg/kg/day by oral gavage. On PND 25 (pre-puberty) and PND 60 (post-puberty), blood for serum and the testes were collected from five male offspring of each group. To determine the relationship between the methylation state of the c-Myc promoter and the expression of the c-Myc gene, some apoptotic-related genes, such as p53 and Bax, the anti-apoptotic Bcl-2 gene, and some growth arrest-related genes, such as BRD7 and GAS1, were examined. Compared with the control ( p < 0.05), at pre-puberty, DBP induces c-Myc hyper-methylation with significant downregulation for c-Myc, p53, Bax genes, and significant upregulation for Bcl-2, BRD7, and GAS1, while at post puberty, the methylation state and expression of c-Myc and apoptosis-related genes returned to control levels in the same sequence with the fold change in the expression of BRD7 and GAS1 genes. These findings suggest that DBP induced a transient pre-pubertal increase in c-Myc promoter methylation that may be associated with disruption of both apoptotic and growth mechanisms in the testes.
Subject(s)
Apoptosis/drug effects , Dibutyl Phthalate/toxicity , Genes, myc/drug effects , Maternal Exposure/statistics & numerical data , Testis/drug effects , Animals , Female , Male , Pregnancy , Rats , Rats, Wistar , Testis/metabolismABSTRACT
The current study was conducted to test the possible ameliorative role of selenium nanoparticles (Se-NPs) against oxidative damage of Leyding cells induced by di-n-butyl phthalate (DBP) in pre-pubertal male rat offspring. Forty-two pregnant female rats treated from gestation day (GD) 12 to postnatal day (PND) 14 day with two doses of Se-NPs (0.2 and 0.5 mg/kg/d) against developmental testicular toxicity induced by DBP (500 mg/kg/d). At PND 25 serum and testes of offspring were collected. Serum LH, the Leydig cells performance [total serum testosterone, LH and testosterone (LH/T) ratio, relative gene expression of insulin-like growth factor-3 (INSL3) and mineralocorticoid receptor (MR)], oxidative stress biomarker malondialdehyde (MDA) and antioxidant machinery [reduced glutathione (GSH), and the relative gene expression of antioxidant enzymes: superoxide dismutase (SOD), glutathione peroxidase (GPx)] were estimated in all groups. The obtained results revealed that maternal exposure to DBP significantly reduced total serum testosterone level, relative mRNA expression of INSL3 and MR genes with observed testicular damage revealed by increasing MDA and depressed levels of GSH and antioxidant enzymes. The histopathological changes include necrosis and desquamation of spermatogoneal cells. Co-administration of Se-NPs high dose along with DBP significantly increased serum testosterone, improved LH/T ratio and the relative mRNA expression of INSL3 and MR genes, decreased the level of MDA, and also improved all the antioxidant enzymes expression levels. In conclusion, Se-NPs could be a potent maternal prophylactic agent against the reduced total serum testosterone level and oxidative damage of Leydig cells induced by DBP via reducing the lipid peroxidation (LPO) and enhancing the antioxidant state in pre-pubertal male rat offspring.
Subject(s)
Nanoparticles , Oxidative Stress/drug effects , Selenium/pharmacology , Testis/drug effects , Animals , Antioxidants/metabolism , Dibutyl Phthalate/toxicity , Dose-Response Relationship, Drug , Female , Glutathione Peroxidase/metabolism , Insulin/genetics , Leydig Cells/drug effects , Leydig Cells/pathology , Lipid Peroxidation/drug effects , Luteinizing Hormone/blood , Male , Malondialdehyde/metabolism , Particle Size , Proteins/genetics , RNA, Messenger/metabolism , Rats , Rats, Wistar , Selenium/administration & dosage , Superoxide Dismutase/metabolism , Testis/pathology , Testosterone/bloodABSTRACT
Tributyltin oxide (TBTO) is a commonly used biocide. The purpose of this study is to correlate the toxicity of TBTO with the alterations of brain neurotransmitters and ATPases. TBTO was given by stomach tube to rats at either 37.5 or 75 mg x kg (-1)for 3 consecutive days. Nervous signs appeared in treated animals and the mortality reached 12 and 30%, respectively. The levels of brain dopamine, norepinephrine and serotonin decreased in a dose-dependent manner. The activities of brain total ATPase, Mg (2+)-ATPase and Na (+)/K (+)- ATPase were suppressed. The activity of Na (+)/K (+)- ATPase was more severely affected than that of Mg (2+)-ATPase. Histopathological changes in brain included hyperaemia, focal haemorrhages in vacuolated myelinated fibres, chromatolysis, or complete necrosis of neurons, degenerative changes, or complete absence of purkinje cells in the cerebellum.
