In Utero Exposure to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Affects the Development of Reproductive System in Mouse

PURPOSE: Exposure of male reproductive organs to 2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) has been reported to cause developmental changes. In this study, we evaluated the effects of in utero TCDD exposure on male reproductive development. MATERIALS AND METHODS: Pregnant C57BL/6 mice were administered a single intraperitoneal injection of TCDD (1microgram/kg) on gestation day (GD) 15. The offspring were examined in the immature stage on postnatal day (PND) 30 and in the mature stage on PND 60. The testes were examined for histological changes, androgen receptor (AR), proliferating cell nuclear antigen (PCNA) and apoptosis following the measurement of morphological changes. RESULTS: Anogenital distance (AGD) and testis weights were reduced by TCDD exposure both on PND 30 and PND 60 while body weights and length of male offspring were not affected by TCDD. The regular sperm developmental stage was impaired with TCDD treatment on PND 30. However, no difference was found between the control group and TCDD groups on PND 60. Simultaneously, the expression of AR was also reduced on PND 30, while it was increased on PND 60 compared with the control group. The expression of PCNA was decreased whereas apoptosis was not affected by TCDD both on PND 30 and PND 60. CONCLUSION: These results suggest that in utero exposure to TCDD influences the development of testes by inhibiting the expression of AR and PCNA. Moreover, the adverse effects of TCDD on male offspring reduced over time.

The Effect and Mechanism of Intravesical Electrical Stimulation in Spinal Cord Injured Rats / 대한비뇨기과학회지

PURPOSE: The objective of this study was to evaluate whether the effect on afferent c-fiber activity is the underlying mechanism of intravesical electrical stimulation (IVES) in spinal cord injured rats. MATERIALS AND METHODS: Thirty five female Sprague-Dawley rats weighting 200-300g each were divided into the normal and spinalized groups. For the spinalized rats, we observed the c-fos expression, and we compared this in the non-IVES group with that in the IVES group. Cystometrograms were performed for all the groups via a suprapubic catheter. RESULTS: After performing IVES in the normal and spinalized rats, the abnormal increases of the intercontraction interval (ICI) and the voiding pressure (VP) were reduced close to the normal range. In the spinalized rats, the number of c-fos positive cells in the dorsal commissure (DCM) decreased in the group that had IVES performed when compared with the non-IVES group. CONCLUSIONS: The IVES reduced the c-fos gene expression in the L6-S1 spinal cord segment and also the bladder hyperreflexia in the spinalized rats through the inhibition of afferent c-fiber activity, in addition to affecting the A delta mechanoreceptors.

Change of Bladder Afferent Neuron after Intravesical Electrical Stimulation / 대한비뇨기과학회지

PURPOSE: There have been reports on the clinical benefits of intravesical electrical stimulation (IVES) in patients with an increased residual urine or reduced bladder capacity. However, studies on the underlying mechanism of IVES have been limited to the A delta afferent and parasympathetic neurons. This study sort to investigate the changes in the expression of the C-fos protein in the thoracolumbar and lumbosacral spinal cord in order to determine the effect of IVES on the C fiber afferent nerve. MATERIALS AND METHODS: Twenty Sprague-Dawley rats were divided into four groups; group 1 (n=5) served as a sham operation, groups 2 (n=5) were instilled with normal saline, groups 3 (n=5) were instilled with 1% acetic acid, and group 4 (n=5) received IVES prior to the administration of 1% acetic acid. The spinal cord was removed at the thoracolumbar (T13-L2) and lumbosacral (L5-S1) levels. Changes in the levels of the C-fos protein in the spinal cord were measured by western-blot analysis. RESULTS: The relative density of the C-fos expression, 2 hours after IVES, was significantly higher, and the fos protein expression induced by IVES was decreased to the sham levels by the 5th day following the IVES. Therefore, it was decided that a 5 day interval between the IVES and the noxious stimulation with acetic acid should be used to avoid the superimposition of C-fos expression. The relative density of the C-fos protein, following noxious stimulation with 1% acetic acid, was significantly higher compared to the saline distension in both the T13-L2 and L5-S1 levels of the spinal cord. However, the IVES prior to the administration of 1% acetic acid significantly decreased the relative density of the C-fos protein at both the T13-L2 and L5-S1 levels of the spinal cord compared to the rats with noxious stimulation alone. CONCLUSIONS: IVES reduces the expression of C-fos, which is mainly conveyed by the unmyelinated C fibers in the noxiously stimulated rats. These results suggest that the bladder C fiber afferent is also involved in modulating the micturition reflex caused by IVES.

Change of Neuropeptides of Bladder Afferents after Intravesical Electrical Stimulation in Spinalized Rat / 대한비뇨기과학회지

PURPOSE: The clinical benefits of intravesical electrical stimulation (IVES), in patients with increased residual urine or reduced bladder capacity, have been reported. However, studies on the underlying mechanism of IVES have been limited to the Adelta afferent in healthy rats. This study investigated the changes in the calcitonin gene- related peptide (CGRP) and substance P (SP) expressions, in the lumbosacral dorsal root ganglia (DRG) and the bladder of spinalized rats, to determine the effect of IVES on the C fiber afferent nerve. MATERIALS AND METHODS: Forty Sprague-Dawley rats were divided into normal controls (n=10); IVES treated normal rats (n=10); spinalized rats (n=10) and IVES treated spinalized rats (n=10). The IVES was performed for 2 weeks (5 days a week), 3 weeks after the spinalization in the spinalized animals. All animals had their DRG removed at the lumbosacral (L5-S1) level. Changes in the CGRP and SP, at the DRG and bladder, were measured by western-blot analysis. RESULTS: The relative density of the CGRP and SP following spinalization was significantly higher than those in the controls in both the DRG and the bladder. However, IVES in the spinalized rat significantly decreased the relative density of the SP, in both the DRG and the bladder, compared to the rats with spinalization alone. IVES in the spinalized rats significantly decreased the relative density of the CGRP, in the DRG only, compared to the rats with spinalization. CONCLUSIONS: IVES significantly reduced the CGRP and SP levels in the DRG of spinalized rats, but only the SP levels in the bladder. CGRP and SP are the main factors contributing to the hyper-excitability of the micturition reflex following spinal cord injury. These results suggest that the bladder C fiber afferents are also involved in modulating the micturition reflex with IVES.