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Effect of growth hormone on recovery from testicular damage induced by methotrexate toxicity in rat
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ETS Abstracts 2008 / Reproductive Toxicology xxx (2008) xxx–xxx
Results: The positive overall association between maternal drug use during pregnancy and infant cardiac defect was confirmed (OR 1.10; 95%CI 1.04–1.17). Significant findings were detected for insulin, antihypertensives, anticonvulsants, salbutamol, clomipramin, and thyroid hormones. Conclusions: Some of the findings are probably due to the underlying disease, and some may be due to multiple testing, but a true causal drug effect to some of the verified findings could not be dismissed. doi:10.1016/j.reprotox.2008.05.024 Effect of growth hormone on recovery from testicular damage induced by methotrexate toxicity in rat Arash Khaki 1 , Marefat Ghaffari Novin 2 , Amir Afshin Khaki 3 , Mohamad Nouri 4 , Chelarc Ozanci 5 1
Department of Veterinary Pathology, Islamic Azad University Tabriz branch, Iran 2 Reproductive Biotechnology Research Center, Avesina Research Institute, Tehran, Iran 3 Department of Anatomical Science, Tabriz University of Medicine Science, Turkey 4 Department of Biochemistry Science, Tabriz University of Medicine Science, Turkey 5 Department of Histology, Acdeniz University, Turkey Introduction: Methotrexate (MTX) is a chemotherapeutic agent that is used for the treatment of a variety of tumors and inflammatory diseases. This study was conducted to evaluate the role of growth hormone (GH) on testicular function recovery induced by MTX in rat. Methods: Fifty male Wistar rats were randomly divided into five groups (n = 10 each), with one group serving as controls. In the GH group, GH was intra peritoneally (IP) administered at a daily dose of 0.3 mg/kg for 28 consecutive days. In the MTX group, MTX was IP administered at weekly doses of 1 mg/kg for 4 weeks. In the protective group, GH and MTX were IP administered together at above doses for 28 days. In the treatment group, MTX was administered at above doses for 4 weeks and GH administration was started 14 days after MTX administration (from 14 days up to 28 days). However, the control group received vehicle (IP). Five rats from each group were sacrificed at day 14 and 28. Spermatozoa were removed from cauda epididymis and analyzed for sperm motility, concentration and viability. Testis tissues were also removed and prepared for histological evaluation. In addition, serum testosterone level was determined by radioimmunoassay on day 14 and 28. Results: This study confirmed MTX had destructive effects on testis germinal cells. There was a significant decrease in sperm count, viability and motility in MTX group when compared with control group (P < 0.05). Testosterone level had significant decrease in MTX, protective and treatment groups when compare to control and GH groups in day 14 and 28 (P < 0.05). GH had recovery effects on testis histology and improve sperm parameters and serum testosterone level (P < 0.05) as compared with MTX group. Conclusion: These results suggested that administration of GH improved testicular function damaged by MTX toxicity.
Maternal stress during pregnancy—An endocrine disruptor increasing vulnerability to stressful life events in the offspring? Sanna L. Kjær 1,2 , Gregers Wegener 1 , Raben Rosenberg 1 , Søren P. Lund 2 , Karin S. Hougaard 2,∗ 1 Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark 2 National Research Centre for the Working Environment, Copenhagen, Denmark
E-mail address: [email protected] (K.S. Hougaard). Introduction: Maternal stress during pregnancy may lead to preterm birth and lower birth weight in children. In animal studies, prenatal stress has also been shown to interfere with neurodevelopment in the offspring and affect, e.g. cognitive function and stress reactivity. These findings point towards increased risk of mental disease later in life. Thus, maternal stress during pregnancy may interfere with development of the fetal nervous system, leaving the individual more vulnerable to develop mental illness later in life, for example in response to stressful life events. In an animal model (rats) this may be envisioned as an enhanced acoustic startle reaction and changed behavior in the forced swim test. Methods: In a series of studies, pregnant rats were stressed during gestation by Chronic Mild Stress (CMS, a variable schedule of stressors). At six months of age, subsets of offspring were tested for the acoustic startle reaction, either during the light or the dark phase, and in the forced swim test. One subset was experimentally na¨ıve at the time of ASR testing, the other subset had months previously been subjected to repeated stressful blood sampling, i.e. a stressful life event. Results: Prenatally stressed offspring displayed increased startle reaction compared to controls, but only in prenatally stressed offspring that had also been blood sampled three months previously – and only when tested during the light (inactive) period of the 24 h cycle. When tested during the dark period, basal acoustic startle was unaffected, but prepulse inhibition was decreased in prenatally stressed animals, with or without blood sampling. Forced swim data remain to be analyzed. Conclusions: A single aversive life event three months previously showed capable of increasing startle reactivity of prenatally stressed offspring, whereas offspring of dams going through a less stressful gestation was largely unaffected by this life event. Prenatal stress decreased prepulse inhibition, irrespective of blood sampling. The ASR is a cross-species reflex. In humans, changes in startle reactivity and prepulse inhibition have been associated with anxiety disorders respectively schizophrenic disease. Furthermore, in some mental illnesses, symptoms changes with the time of the 24 h cycle. The results indicate that circumstances in the very beginning of life may affect the individual’s susceptibility towards development of mental disease in life after birth. We suggest that stress in the maternal organism works as an endocrine disruptor in the fetus, i.e. the prenatal environment forms part of the explanation of the considerable individual variation in the development of psychopathology. doi:10.1016/j.reprotox.2008.05.026
doi:10.1016/j.reprotox.2008.05.025
RTX 6115 1–22
ETS Abstracts 2008 / Reproductive Toxicology xxx (2008) xxx–xxx
Results: The positive overall association between maternal drug use during pregnancy and infant cardiac defect was confirmed (OR 1.10; 95%CI 1.04–1.17). Significant findings were detected for insulin, antihypertensives, anticonvulsants, salbutamol, clomipramin, and thyroid hormones. Conclusions: Some of the findings are probably due to the underlying disease, and some may be due to multiple testing, but a true causal drug effect to some of the verified findings could not be dismissed. doi:10.1016/j.reprotox.2008.05.024 Effect of growth hormone on recovery from testicular damage induced by methotrexate toxicity in rat Arash Khaki 1 , Marefat Ghaffari Novin 2 , Amir Afshin Khaki 3 , Mohamad Nouri 4 , Chelarc Ozanci 5 1
Department of Veterinary Pathology, Islamic Azad University Tabriz branch, Iran 2 Reproductive Biotechnology Research Center, Avesina Research Institute, Tehran, Iran 3 Department of Anatomical Science, Tabriz University of Medicine Science, Turkey 4 Department of Biochemistry Science, Tabriz University of Medicine Science, Turkey 5 Department of Histology, Acdeniz University, Turkey Introduction: Methotrexate (MTX) is a chemotherapeutic agent that is used for the treatment of a variety of tumors and inflammatory diseases. This study was conducted to evaluate the role of growth hormone (GH) on testicular function recovery induced by MTX in rat. Methods: Fifty male Wistar rats were randomly divided into five groups (n = 10 each), with one group serving as controls. In the GH group, GH was intra peritoneally (IP) administered at a daily dose of 0.3 mg/kg for 28 consecutive days. In the MTX group, MTX was IP administered at weekly doses of 1 mg/kg for 4 weeks. In the protective group, GH and MTX were IP administered together at above doses for 28 days. In the treatment group, MTX was administered at above doses for 4 weeks and GH administration was started 14 days after MTX administration (from 14 days up to 28 days). However, the control group received vehicle (IP). Five rats from each group were sacrificed at day 14 and 28. Spermatozoa were removed from cauda epididymis and analyzed for sperm motility, concentration and viability. Testis tissues were also removed and prepared for histological evaluation. In addition, serum testosterone level was determined by radioimmunoassay on day 14 and 28. Results: This study confirmed MTX had destructive effects on testis germinal cells. There was a significant decrease in sperm count, viability and motility in MTX group when compared with control group (P < 0.05). Testosterone level had significant decrease in MTX, protective and treatment groups when compare to control and GH groups in day 14 and 28 (P < 0.05). GH had recovery effects on testis histology and improve sperm parameters and serum testosterone level (P < 0.05) as compared with MTX group. Conclusion: These results suggested that administration of GH improved testicular function damaged by MTX toxicity.
Maternal stress during pregnancy—An endocrine disruptor increasing vulnerability to stressful life events in the offspring? Sanna L. Kjær 1,2 , Gregers Wegener 1 , Raben Rosenberg 1 , Søren P. Lund 2 , Karin S. Hougaard 2,∗ 1 Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Denmark 2 National Research Centre for the Working Environment, Copenhagen, Denmark
E-mail address: [email protected] (K.S. Hougaard). Introduction: Maternal stress during pregnancy may lead to preterm birth and lower birth weight in children. In animal studies, prenatal stress has also been shown to interfere with neurodevelopment in the offspring and affect, e.g. cognitive function and stress reactivity. These findings point towards increased risk of mental disease later in life. Thus, maternal stress during pregnancy may interfere with development of the fetal nervous system, leaving the individual more vulnerable to develop mental illness later in life, for example in response to stressful life events. In an animal model (rats) this may be envisioned as an enhanced acoustic startle reaction and changed behavior in the forced swim test. Methods: In a series of studies, pregnant rats were stressed during gestation by Chronic Mild Stress (CMS, a variable schedule of stressors). At six months of age, subsets of offspring were tested for the acoustic startle reaction, either during the light or the dark phase, and in the forced swim test. One subset was experimentally na¨ıve at the time of ASR testing, the other subset had months previously been subjected to repeated stressful blood sampling, i.e. a stressful life event. Results: Prenatally stressed offspring displayed increased startle reaction compared to controls, but only in prenatally stressed offspring that had also been blood sampled three months previously – and only when tested during the light (inactive) period of the 24 h cycle. When tested during the dark period, basal acoustic startle was unaffected, but prepulse inhibition was decreased in prenatally stressed animals, with or without blood sampling. Forced swim data remain to be analyzed. Conclusions: A single aversive life event three months previously showed capable of increasing startle reactivity of prenatally stressed offspring, whereas offspring of dams going through a less stressful gestation was largely unaffected by this life event. Prenatal stress decreased prepulse inhibition, irrespective of blood sampling. The ASR is a cross-species reflex. In humans, changes in startle reactivity and prepulse inhibition have been associated with anxiety disorders respectively schizophrenic disease. Furthermore, in some mental illnesses, symptoms changes with the time of the 24 h cycle. The results indicate that circumstances in the very beginning of life may affect the individual’s susceptibility towards development of mental disease in life after birth. We suggest that stress in the maternal organism works as an endocrine disruptor in the fetus, i.e. the prenatal environment forms part of the explanation of the considerable individual variation in the development of psychopathology. doi:10.1016/j.reprotox.2008.05.026
doi:10.1016/j.reprotox.2008.05.025
RTX 6115 1–22