RESUMO
Polychlorinated biphenyls (PCBs) are environmental pollutants that are quite toxic to biological systems. This study examined the inhibitory effect of PCB126 and PCB114 on testicular steroidogenesis in male rats. Male Sprague Dawley rats received weekly intraperitoneal injections of PCB126 (0.2 mg/kg) or PCB114 (20 mg/kg) or vehicle (corn oil). Animals from each group were sacrificed at 2, 5 and 8 weeks after the injections. Blood and testis tissue samples were collected for the hormone assay, Western blotting and reverse transcriptase polymerase chain reaction (RT-PCR). The testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels were assayed, and the expression levels of the mRNA and proteins associated with the testosterone biosynthesis pathway were measured to determine the effect of PCB126 and PCB114 on testicular steroidogenesis. The results showed that the testis weight was significantly higher in the PCB126-treated rats given eight shots. Moreover, the serum testosterone levels were significantly lower in the PCB126 and PCB114-treated groups than the control. The transcription and translation levels of P450(17alpha) and P450(scc) were significantly lower in the PCB126-treated groups than the control. These results suggest that PCB126 may affect testicular steroidogenesis by downregulating P450(17alpha), P450(scc) and have inhibitory effect on the testicular functions.
Assuntos
Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Bifenilos Policlorados/farmacologia , Esteroide 17-alfa-Hidroxilase/metabolismo , Esteroides/biossíntese , Testículo/efeitos dos fármacos , Animais , Western Blotting , Enzima de Clivagem da Cadeia Lateral do Colesterol/biossíntese , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Regulação para Baixo/efeitos dos fármacos , Hormônio Foliculoestimulante/biossíntese , Hormônio Foliculoestimulante/sangue , Perfilação da Expressão Gênica , Humanos , Hormônio Luteinizante/biossíntese , Hormônio Luteinizante/sangue , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Esteroide 17-alfa-Hidroxilase/biossíntese , Esteroide 17-alfa-Hidroxilase/genética , Esteroides/antagonistas & inibidores , Testículo/anatomia & histologia , Testículo/metabolismo , Testosterona/biossíntese , Testosterona/sangueRESUMO
Polychlorinated biphenyls are environmental pollutants that are toxic to many biological systems. This study examined whether or not PCB126 and PCB114 have adverse effects on the serum thyroxine level and the serum proteome in rats. The results showed a lower serum total thyroxine level in the PCB126 and PCB114-treated groups than the control. Western blotting showed that the levels of transthyretin expression were significantly higher in the PCB-treated group than the control group. These results suggest that the PCB-mediated hypothyroidism is caused by the displacement of thyroxine from transthyretin.
Assuntos
Hipotireoidismo/induzido quimicamente , Bifenilos Policlorados/toxicidade , Pré-Albumina/metabolismo , Regulação para Cima/efeitos dos fármacos , Animais , Masculino , Pré-Albumina/genética , Ratos , Ratos Sprague-Dawley , Tiroxina/sangueRESUMO
We identified a 3.4-kb 5'-flanking region of the rPL-I gene and examined its promoter activity using rat trophoblast Rcho-1 cells. A regulatory element between base pairs (bp) -2,487 and -2,310 in the 5'-flanking region was essential for maximum promoter activity of the rPL-I gene. This regulatory element was further characterized between bp -2,443 to -2,415 and -2,374 to -2,345. Electrophoretic mobility shift analysis showed that the interaction of nuclear extract proteins from differentiated Rcho-1 cells was inhibited by competition with a GATA-like sequence in the promoter, but not by a mutated GATA sequence. Moreover, the promoter activity of 2487 eLuc containing two novel GATA sites was significantly elevated by co-transfection of a GATA-2 expression vector in proliferating Rcho-1 cells. Our results demonstrate that GATA-2 is involved in multiple promoter regions to activate the specific expression of the rPL-I gene in placental tissue.
Assuntos
Fator de Transcrição GATA2/metabolismo , Regulação da Expressão Gênica , Lactogênio Placentário/biossíntese , Elementos Reguladores de Transcrição , Trofoblastos/fisiologia , Região 5'-Flanqueadora , Animais , Fusão Gênica Artificial , Sítios de Ligação , Ensaio de Desvio de Mobilidade Eletroforética , Genes Reporter , Luciferases/genética , Luciferases/metabolismo , Ligação Proteica , RatosRESUMO
The placenta produces several growth factors, including placenta growth factor (PlGF), which are essential for placenta growth and fetal growth. Diabetic pregnancy induces the abnormal placental growth and fetal development. This study investigated whether diabetes in pregnant rats induces changes in PlGF expression in the placenta. Diabetes was induced by a single intravenous injection of streptozotocin (35 mg/kg body weight) on day 0 of pregnancy, blood and tissue samples were collected on day 20 of pregnancy. In the diabetic group, maternal body weight and fetal weight significantly decreased compared to controls. RT-PCR and Western blot analyses showed that expression of PlGF was significantly decreased in placenta by streptozotocin treatment. Immunohistochemical study showed that the positive signal of PlGF in trophoblast cells was decreased in the diabetic group compared to controls. These findings demonstrate the decline of PlGF in the placenta in diabetic pregnancy.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Diabetes Gestacional/metabolismo , Placenta/metabolismo , Proteínas da Gravidez/metabolismo , Animais , Glicemia/metabolismo , Western Blotting , Peso Corporal/fisiologia , Diabetes Mellitus Experimental/sangue , Diabetes Gestacional/sangue , Feminino , Peso Fetal/fisiologia , Feto , Imuno-Histoquímica , Masculino , Tamanho do Órgão/fisiologia , Fator de Crescimento Placentário , Gravidez , Proteínas da Gravidez/biossíntese , Proteínas da Gravidez/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
A male deformed Korean native calf was examined macroscopically. The deformed calf had no caudal vertebral columns from 5th lumbar vertebra, sacrum and coccygeal vertebrae. The spinal cord was terminated in the vertebral foramen of the 3rd lumbar vertebra. The cervical vertebrae had scoliosis and the 3rd and 4th cervical vertebrae were fused. The 2nd and 3rd lumbar vertebrae were fused and the left and right transverse processes of the 4th lumbar vertebra articulated with ala of the ilium. The rectum was greatly expanded by the imperforate anus and a rectourethral fistula was formed between the rectum and urethra. The deformed calf was recorded as a first documentation of sacrocaudal agenesis confirmed in a Korean native calf.