• Childhood Kidney Diseases
• /
• v.3 no.2
• /
• pp.109-116
• /
• 1999

Purpose: Insulin-like growth factor(IGF)-I and -II are peptide growth factor whose activity is modulated by interaction with the family of six IGF-binding proteins(IGFBPs). IGF-I is detected in rat kidney and has metabolic and growth effects. This study was designed to examine temporal expression of IGFBPs in kidney during renal development and postischemic regeneration in rat. Method: The expression of IGFBPs in kidney during renal development from 15th day of gestation to adult life by using Northern blot analysis. We also examined the renal IGF-IGFBP axis in uremic rat by using Northern blot and immunohistochemistry. Results: The mRNA of IGFBP-1 and -3 were not or barely detected in fetal stages. However, the mRNA level of IGFBP-1 and -3 were increased gradually from day 7 after birth to adult. In contrast, the mRNA of IGFBP-2 and -5 were highly expressed in fetal stages and maintained almost same levels until day 7 (IGFBP-2) or day 30 (IGFBP-5) after birth, then their levels decreased markedly. The mRNA of IGFBP-4 were expressed moderately in fetal kidney and increased gradually after birth. Interestingly, the mRNA of IGFBP-1 and-4 were induced up to 3-5 fold during maximum regeneration period and were recovered to normal levels after acute ischemic injury. In contrast, the mRNA level of IGFBP-3 and-IGFBPrP-1 were decreased slightly at 1 day after ischemic injury, then recovered to normal level during maximum regeneration period. Conclusion: There were differential expressions of IGFBPs in kidney that can modulate IGF action on developing, differentiating, maintaining, and regenerating renal structure and function.

• Korean Journal of Veterinary Research
• /
• v.43 no.4
• /
• pp.657-666
• /
• 2003

The present study was undertaken to evaluate the potential adverse effects of 2-BP on pregnant dams and embryo-fetal development after maternal exposure during the gestational days (GD) 6 through 19 in Sprague-Dawley rats. The test chemical was administered subcutaneously to pregnant rats at dose levels of 0, 375, 750 and 1250 mg/kg/day. During the test period, clinical signs, mortality, body weights and food consumption were examined. All dams were subjected to caesarean section on GD 20 and their fetuses were examined for external, visceral and skeletal abnormalities. At above 750 mg/kg, toxic effects including signs of toxicity, suppressed body weight, decreased gravid uterine weight and reduced food intake were observed in pregnant dams. An increase in the fetal deaths, a decrease in the litter size, a reduction in the fetal body weight and an increase in the incidence of fetal morphological alterations were also found. There were no adverse effects on either pregnant dams or embryo-fetal development at a dose level of 375 mg/kg. These results suggest that a 14-day subcutaneous dose of 2-BP is embryolethal and teratogenic at above 750 mg/kg/day in pregnant rats. In the present experimental condition, the no-observed-adverse-effect level of 2-BP is considered to be 375 mg/kg/day for dams and embryo-fetuses, respectively.

• Reproductive and Developmental Biology
• /
• v.31 no.2
• /
• pp.109-113
• /
• 2007

This study was conducted to evaluate the effect of cytochalasin B (CB) treatment in the activation medium on the development of somatic cell nuclear transfer (SCNT) rat embryos. Fetal fibroblast cells were isolated from a Day 14.5 fetus, and the oocytes for recipient cytoplasm were recovered from 4-week old Sprague Dawley rats. After enucleation and nuclear injection, the reconstructed oocytes were immediately exposed to activation medium consisting of 10 mM $SrCl_2$ with or without CB for 4 hr, and formation of pseudo-pronucleus (PPN) was checked at 18 hr after activation. Then, they were transferred into day 1 pseudopregnant recipients (Hooded Wistar) or cultured for 5 days to check their developmental competence in vivo or in vitro. The number of PPN was not affected by CB treatment during the activation. However, CB treatment supported pre-implantation development of rat SCNT embryos. Embryos generated by the procedures of SCNT were also capable of implanting, with 1 implantation scar found from a recipient following the transfer of 87 SCNT embryos to four foster mothers. The result of the present study shows that rat SCNT embryo can develop to post-implantation stage following treatment with CB.

• Applied Microscopy
• /
• v.15 no.1
• /
• pp.59-70
• /
• 1985

Morphogenesis of rat retina was studied by light and electron microscope from day 14 of gestation to 55 days after birth. The results indicate as follows: 1. At the outer border of the neuroblastic layer at the 14th day of gestation, cells she wed active mitotic figures which result in the increases of thickness and differentiations of this layer. 2. At birth, rat retina is still in a premature state. But, it is begining to approach its adult condition in appearance till the 9th postnatal day. Particulary photosensitive cells are fully developed by the 14th postnatal day, so they are functional from now on. 3. It is observed that the pigment epithelium begins differentiation at the fetal period, but is not functional urtil birth 4. The pigment epithelium differentiates earlier than the neuroblastic layer. It is suggested that these two layers are so closely associated that the pigment epithelium takes part in the differentiations of the neuroblastic layer. In conclusion, rat retina is differentiated soon after the optic cup formation before the 14th day of gestation, but even new born rat retina is not functional, and then it has function as photoreceptors coincided with the eye opening.

• Reproductive and Developmental Biology
• /
• v.29 no.4
• /
• pp.229-234
• /
• 2005

Methods for activation of reconstructed oocytes were examined for the production of nuclear transfer (NT) rat embryos using fetal neural stem cells as donor. Neural stem cells were isolated from Day 14.5 rat fetuses, and the oocytes for recipient cytoplasm were recovered from 4-week old Sprague Dawley rats. After enucleation and nuclear injection, the reconstructed oocytes were immediately exposed to activation medium consisting of 10 mM $SrCl_2$ for 4 h (immediate activation after injection; IAI), or cultured in vitro for $2\~3$ h before activation treatment (injection before activation; IBA). Pre-activated oocytes were also used for NT to test reprogramming potential of artificially activated oocytes. The oocytes were grouped as IIA (immediate injection after activation) and ABI (activation $2\~3$ h before injection). Following NT, the oocytes were cultured in vitro. Development of the NT embryos was monitored at 44 and 119 h after activation. The embryos in groups IAI, mA, and IIA were cleaved to the 2-cell stage at the rates of $36.6\%\;(15/41),\;39.5\%\;(17/43)\;and\;46.3\%$ (25/54), respectively. However, in the ABI group, only one embryo ($1.8\%$, 1/55) was cleaved after activation. After in vitro culture, two NT embryos from IAI group had developed to the morula stage $(4.9\%\cdot2/41)$. However, no morula or blastocyst was obtained in the other groups. These results suggest that immediate activation after injection (IAI) method may be used for the production of rat somatic cell NT embryos.

• Childhood Kidney Diseases
• /
• v.21 no.1
• /
• pp.1-7
• /
• 2017

Mitogen-activated protein kinases (MAPKs) play important roles in various cellular functions including proliferation, differentiation, and apoptosis. We showed that MAPKs are developmentally regulated in the rat kidney. p38 MAPK (p38) and extracellular signal-regulated kinase (ERK) were strongly expressed in the fetal kidney, whereas c-Jun N-terminal kinase (JNK) was detected predominantly in the adult kidney. The inhibition of p38 or ERK in organ culture resulted in reduced nephron formation with or without reduced kidney size. On the other hand, persistent fetal expression pattern of MAPKs, i.e., upregulation of p38 and ERK and downregulation of JNK, was observed in the cyst epithelium of human renal dysplasia, ovine fetal obstructive uropathy, and pcy mice, a model of polycystic kidney disease. Furthermore, activated p38 and ERK induced by cyclic stretch mediated proliferation and $TGF-{\beta}1$ expression in ureteric bud cells, probably leading to cyst formation and dysplastic changes. Inhibition of ERK slowed the disease progression in pcy mice. Finally, ERK and p38 were inactivated in the early embryonic kidney subjected to maternal nutrient restriction, characterized by reduced ureteric branching and nephron number. Thus, MAPKs mediate the development of normal and diseased kidney. Their modulation may result in novel therapeutic strategies against developmental abnormalities of the kidney.

• Toxicological Research
• /
• v.17 no.1
• /
• pp.27-32
• /
• 2001

Korean ginseng products have been fumigated with ethylene oxide (EO) for sterilization and prolongation of storage periods. However, there had been controversies indicating that consumption of EO treated foods might cause harmful effects in human. In Korea, the use EO gas for food treatment was banned in 1991. Since then, irradiation technique has been developed as an alternative. This study was carried out to evaluate the safety of irradiated ginseng on embryo and fetal developmental toxicity effects in rats. Either EO gas fumigated or $\gamma$-irradiated ginseng was administered to pregnant Wistar rats by oral gavage from gestational day 7 to 17. The amount of irradiation used in this study was 5, 10 and 30 kGy, respectively. There were no treatment related changes of dams in deaths, clinical signs, food consumption and body/organ weight. No treatment related changes in implantation ratio, litter size, sex ratio and body/organ weight of fetuses were observed. Also, no F1fetuses with external, visceral, head and skeletal mal-formation were observed. The results of this study showed that $\gamma$-irradiated ginseng, up to 30 kGy, has no adverse effects on fetal development of rats.

• Biomolecules & Therapeutics
• /
• v.6 no.2
• /
• pp.151-158
• /
• 1998

Aspalatone, a new antithrombotic agent, was administered orally to pregnant Sprague-Dawley rats during the organogenetic period at dose levels of 0, 20, 100 and 500 mg/kg/day. All dams were subjected to caesarean section on day 20 of pregnancy. Effects of test substance on dams and embryonic development of F1 fetuses were examined There were treatment-related decreases in body weight and food consumption in the 500 mg/kg group. There was a increase in the spleen weight in the 100 and 500 mg/kg groups. Develo-pmental toxicity was evident as decreased fetal body weights and increased fetal malformations in the 500 mg/ kg group. External and skeletal malformations of fetuses occurred at an incidence of 1 and 8.2%, respectively. In addition, there was a delay in ossification of sternebrae and sacrocaudal vertebrae in the 500 mg/kg group. The results show that the no observed adverse effect dose level (NOAEL) for maternal toxicity was 20 mg/kg/ day and for developmental toxicity was 100 mg/kg/day.

• Animal cells and systems
• /
• v.6 no.3
• /
• pp.247-252
• /
• 2002

The effect of paraquat (PQ, 1,1＇-dimethyl-4,4＇-bipyridium) on the histogene-sis and glycoconjugates (GCs) properties of the pyloric region of the stomach in a perinatal rat was examined by histological and histochemical methods. Oral administration of PQ (9 mg/kg per day in 0.2 mL of D.W.) on 7 to 14 days of gestation revealed growth retardation with significant reductions in the length of pyloric gland and their pit. As for histochemical properties of GCs in the pyloric region of the stomach, the PQ-treated rats showed some differences, such as delayed initial appearance of the sulfated GCs and lectin affinities compared with the vehicle group. These different GCs properties in the surface and gastric pit were usually detected in the fetal rats and more prominent and evident differences were revealed in the gland epithelium of the early postnatal rat. These results suggest that maternal PQ administration causes intrauterine growth retardation asso-ciated with delayed histogenesis and GCs immaturation of pyloric mucosa in developing rat.

• The Korean Journal of Pharmacology
• /
• v.27 no.1
• /
• pp.7-12
• /
• 1991

We measured the developmental increase of tyrosine hydroxylase(TH) activity and dopamine content with high performance liquid chromatography with electrochemical detection(HPLC-EC) in dissociated cultures of fetal rat brainstem(E14). TH activity and dopamine content increased progressively upto 7 days in vitro, when the effects of various drugs on the dopamine contents were studied. ${\alpha}-Methyl-p-tyrosine$, a TH inhibitor and NSD-1015, an inhibitor of aromatic amiono acid decarboxylase effectively depleted dopamine contents. Dopamine contents were depleted by reserpine and increased by pargyline. When cultures grown for 1 week in control medium were then exposed to tetrodotoxin$(0.1\;{\mu}M$) for 7 days, exposure to tetrodotoxin markedly decreased TH activity. All the above results indicate that dopamine metabolism in the cultered cells reflect reliably the property of brain dopamine metabolism. We suggest that measuring TH activity and dopamine content in brainstem culture with HPLC-EC can be useful tool in the study of pharmacology as well as toxicology of the central dopaminergic system.