• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2002년도 Current Trends in Toxicological Sciences
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• pp.48-64
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• 2002

The primary recognized health risk from common deficiencies in glucose-6-phosphate dehydrogenase (G6PD), a cytoprotective enzyme for oxidative stress, is red blood cell hemolysis. Here we show that litters from untreated pregnant mutant mice with a hereditary G6PD deficiency had increased prenatal (fetal resorptions) and postnatal death. When treated with the anticonvulsant drug phenytoin, a human teratogen that is commonly used in pregnant women and causes embryonic oxidative stress, G6PD-deficient dams had higher embryonic DNA oxidation and more fetal death and birth defects. The reported G6PD gene mutation was confirmed and used to genotype fetal resorptions, which were primarily G6PD deficient. This is the first evidence that G6PD is a developmentally critical cytoprotective enzyme for both endogenous and xenobiotic-initiated embryopathic oxidative stress and DNA damage. G6PD deficiencies accordingly may have a broader biological relevance as important determinants of infertility, in utero and postnatal death, and teratogenesis.-Nicol, C. J., Zielenski, J., Tsui, L.-C., Wells, P. G. An embryoprotective role for glucose-6-phosphate dehydrogenase in developmental oxidative stress and chemical teratogenesis.

• Journal of Animal Science and Technology
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• 제50권1호
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• pp.45-56
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• 2008

본 연구는 생후 발달 과정 동안 monocarboxylate transporter(MCT) isoform과 MCT의 발현 조절 단백질로 알려진 basigin(Bsg)과 embigin의 mRNA 발현을 흰쥐의 부정소에서 부위별로 real-time PCR 방법을 사용하여 알아보았으며, 에스트로젠과 에스트로젠 수용체 α의 작용에 의해 MCT1 발현이 조절되는지를 알아보기 위해 estrogen receptor α knockout(αERKO) 마우스를 이용하여 immunohistochemistry 방법을 통해 탐구하였다. 본 연구 결과는 다양한 MCT isoform(MCT1, 2, 3, 4와 8), Bsg과 embigin의 mRNA 발현이 부정소의 부위별로 연령에 따라 다르게 나타나며, 부정소에서 MCT1 단백질 발현은 corpus와 caudal 부위에서 apical 지역에 한정되어 나타나는 것을 보여 주었다. 또한 부정소에서 MCT1 단백질 발현은 에스트로젠 수용체 α의 존재 여부와 상관 없음이 보여졌다. 따라서, 본 연구는 MCT가 남성 생식기관인 부정소에서 정자 성숙과 저장을 위한 적절한 환경을 형성함으로써 남성 생식력의 유지에 관여 할 수 있음을 시사한다. (색인어 : Epididymis, Monocarboxylate transporter, Basigin, Embigin)

• 한국발생생물학회지:발생과생식
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• 제24권3호
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• pp.159-165
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• 2020

Previously, we reported adverse effects of low-dose nonylphenol (NP) exposure on the reproductive parameters of F1 female mice. In the present study we further investigated the pathohistological effect of NP exposure on the reproductive organs in F1 female mice. NP exposures were continuously conducted from parental pre-mating period until the postnatal day (PND) 33 of F1 offspring for vaginal examination. Mice were sacrificed on PND 30 and the reproductive tissue weights were measured. The initial (at PND 21) body weights of the NP-50 group animals were significantly lower than those of control group animals, and the weight deficit were recovered when the terminal (PND 33) body weights were measured. Early vaginal opening was found in NP group animals (p<0.05). Pathohistological studies revealed that NP-treated F1 animals showed prominent increase in the ovarian follicle numbers (p<0.01), and decrease in the diameter of uterine myometrium (p<0.01), and increase in the diameter of luminal epithelium (p<0.05). The present study demonstrated that the subchronic low-dose NP exposure induced early beginning of puberty and pathohistological abnormalities in ovary and uterus of F1 mice. Further studies are needed to achieve a better understanding on the action mechanism of NP in pubertal onset and to find a way to avoid a hazardous situation provoked by NP exposure.

• 한국발생생물학회지:발생과생식
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• 제23권3호
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• pp.255-262
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• 2019

Previously, we reported negative effects of low-dose nonylphenol (NP) exposure on the reproductive organs of F1 male mice. In the present study was further investigated the endocrine disrupting effect of NP exposure to F2 generation male mice. Mice were divided into 2 groups; (1) CON, control animals and (2) NP-50 ($50{\mu}g/L$), animals were treated with NP via drinking water. NP exposures were continuously conducted from parental pre-mating period until the postnatal day (PND) 55 of F2 offsprings. Mice were sacrificed on PND 55 and the reproductive tissue weights were measured. The initial (at PND 21) and terminal (PND 55) body weights of the NP-50 group animals were not significantly different from those of control group animals. NP exposure fail to induce a significant weight change of the testes, seminal vesicle and prostate except absolute epididymal weight (p<0.05). However, pathohistological studies revealed that NP-treated F2 animals showed evident decrease in seminiferous tubule diameters, reduced luminal area and number of germ cells. Also, sloughing morphologies in the tubules were notable. In the caudal epididymis, fewer mature sperms and swollen epithelial cells were found in the NP-treated group. The present study demonstrated that the subchronic low-dose NP exposure induced pathohistological abnormalities in testis and epididymis of F2 mice, and we assumed that these 'qualitative' changes in reproductive tissues could be derived from the epigenetic modifications such as DNA methylation, histone modification, altered DNA accessibility and chromatin structure. Further studies are needed to achieve a better understanding on the multi- or trans-generational effects of NP on the reproductive health and a human application.

• BMB Reports
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• 제54권6호
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• pp.317-322
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• 2021

CCCTC-binding factor (CTCF), a zinc finger protein, is a transcription factor and regulator of chromatin structure. Forebrain excitatory neuron-specific CTCF deficiency contributes to inflammation via enhanced transcription of inflammation-related genes in the cortex and hippocampus. However, little is known about the long-term effect of CTCF deficiency on postnatal neurons, astrocytes, or microglia in the hippocampus of adult mice. To address this, we knocked out the Ctcf gene in forebrain glutamatergic neurons (Ctcf cKO) by crossing Ctcf-floxed mice with Camk2a-Cre mice and examined the hippocampi of 7.5-10-month-old male mice using immunofluorescence microscopy. We found obvious neuronal cell death and reactive gliosis in the hippocampal cornu ammonis (CA)1 in 7.5-10-month-old cKO mice. Prominent rod-shaped microglia that participate in immune surveillance were observed in the stratum pyramidale and radiatum layer, indicating a potential increase in inflammatory mediators released by hippocampal neurons. Although neuronal loss was not observed in CA3, and dentate gyrus (DG) CTCF depletion induced a significant increase in the number of microglia in the stratum oriens of CA3 and reactive microgliosis and astrogliosis in the molecular layer and hilus of the DG in 7.5-10-month-old cKO mice. These results suggest that long-term Ctcf deletion from forebrain excitatory neurons may contribute to reactive gliosis induced by neuronal damage and consequent neuronal loss in the hippocampal CA1, DG, and CA3 in sequence over 7 months of age.

• Journal of Veterinary Science
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• 제19권6호
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• pp.750-758
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• 2018

Influenza virus infection is a zoonosis that has great socioeconomic effects worldwide. Influenza infection induces respiratory symptoms, while the influenza virus can infect brain and leave central nervous system sequelae. As children are more vulnerable to infection, they are at risk of long-term neurological effects once their brains are infected. We previously demonstrated that functional changes in hippocampal neurons were observed in mice recovered from neonatal influenza infection. In this study, we investigated changes in myelination properties that could affect neural dysfunction. Mice were infected with the influenza virus on postnatal day 5. Tissues were harvested from recovered mice 21-days post-infection. The expression levels for myelin basic protein (MBP) were determined, and immunohistochemical staining and transmission electron microscopy were performed. Real-time polymerase chain reaction and Western blot analyses showed that mRNA and protein expressions increased in the hippocampus and cerebellum of recovered mice. Increased MBP-staining signal was observed in the recovered mouse brain. By calculating the relative thickness of myelin sheath in relation to nerve fiber diameter (G-ratio) from electron photomicrographs, an increased G-ratio was observed in both the hippocampus and cerebellum of recovered mice. Influenza infection in oligodendrocyte-enriched primary brain cell cultures showed that proinflammatory cytokines may induce MBP upregulation. These results suggested that increased MBP expression could be a compensatory change related to hypomyelination, which may underlie neural dysfunction in recovered mice. In summary, the present results demonstrate that influenza infection during the neonatal period affects myelination and further induces functional changes in influenza-recovered mouse brain.

• 한국발생생물학회지:발생과생식
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• 제23권2호
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• pp.93-99
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• 2019

Nonylphenols (NPs) are widely used industrial materials, and are considered as potent endocrine disrupting chemical. Present study was undertaken to clarify the effect of subchronic low-dose NP exposure to F1 generation male mice. Mice were divided into 2 groups; (1) CON, control animals and (2) NP-50 ($50{\mu}g/L$), animals were treated with NP via drinking water. NP exposures were continuously conducted from parental pre-mating period until the postnatal day (PND) 55 of F1 offsprings. Mice were sacrificed on PND 55 and the tissue weights were measured. The initial body weights (at PND 21) and terminal body weights (PND 55) of the NP-50 animals were significantly lower than those of control animals (p<0.05). NP exposure induced a significant increase in the absolute weight of the testes (p<0.05). Conversely, the NP exposure caused significant decrease in the absolute weights of the epididymis (p<0.01), prostate (p<0.05) and seminal vesicle (p<0.05). Histopathological studies revealed that NP-treated animals exerted decreased seminiferous tubule diameters, reduced luminal area, and lower number of germ cells. Also some sloughing morphologies in the tubules were observed. In the caudal epididymis, fewer mature sperms and swollen epithelial cells were found in the NP-treated group. Our results confirmed that the subchronic low-dose NP exposure altered some male parameters and induced histopathological abnormalities in testis and epididymis of F1 mice. Since the NP dose used in this study is close to the average human daily NP exposure, our results could provide practically meaningful understanding of adverse effect of EDC in human.

• Toxicological Research
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• 제22권2호
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• pp.87-93
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• 2006

The KFDA (Korea Food & Drug Administration) has performed a collaborative toxico-genomics project since 2003. Its aim is to construct a toxicologenomic database of 12 hepatotoxic compounds from mice livers. Phenylbutazone which is non-steroidal anti-inflammatory drug was assigned. It was administered at low (0.0238 mg/kg) and at high (0.238 mg/kg) dose (5 mice per group) orally to the postnatal 6 weeks ICR mice, then the serum and liver were collected at the indicated time (6, 24 and 72 h) after administration. Serum biochemical markers for liver toxicity were measured and histopathologic studies also were carried out. The gene expression profiling was carried out by using Applied Biosystems 1700 Full Genome Expression Mouse. The 2-way ANOVA was used to find genes that reflected phenylbutazone-induced acute toxicity or dose-dependant changes. By self-organization maps (SOM), we identified groups with unique gene expression patterns, some of them are supposed to be related to phenylbutazone induced toxicity, including lipid metabolism abnormality, oxidative stress, cell death and cytoskeleton destruction.

• Molecules and Cells
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• 제41권8호
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• pp.753-761
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• 2018

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is identified as a signaling adaptor protein that regulates bone metabolism, immunity, and the development of several tissues. Therefore, its functions are closely associated with multiple diseases. TRAF6 is also involved in the regulation of hematopoiesis under steady-state conditions, but the role of TRAF6 in modulating hematopoietic stem and progenitor cells (HSPCs) during the developmental stages remains unknown. Here, we report that the deletion of TRAF6 in hematopoietic lineage cells resulted in the upregulation of HSPCs in the fetal liver at the prenatal period. However, in the early postnatal period, deletion of TRAF6 drastically diminished HSPCs in the bone marrow (BM), with severe defects in BM development and extramedullary hematopoiesis in the spleen being identified. In the analysis of adult HSPCs in a BM reconstitution setting, TRAF6 played no significant role in HSPC homeostasis, albeit it affected the development of T cells. Taken together, our results suggest that the role of TRAF6 in regulating HSPCs is altered in a spatial and temporal manner during the developmental course of mice.

• 대한소아치과학회지
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• 제31권4호
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• pp.651-658
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• 2004

Runx2는 runt gene family에 속하는 전사조절 인자로써 뼈의 형성과 골아세포의 분화에 중요한 역할을 담당하고 있다. Runx2-haploinsufficency는 쇄골의 저형성 및 두개 봉합의 지연을 특징으로 하는 쇄골두개 이형성증을 일으키며, 치아에 있어서는 법랑질의 저형성, 영구치 맹출지연 등을 보인다. 이에, 치아의 발육 및 맹출에 미치는 Runx2의 영향을 알아보기 위해 in situ hybridization 방법으로 태생 1, 4, 7, 14, 21일 된 쥐의 하악 및 제1대구치를 사용하여 실험을 실시하였다. Runx2-full length는 태생 1일과 4일에 치낭 및 그 주위조직에 보이지만 Runx2-typeII는 보이지 않았다 Runx2-full length는 태생 7일에 치관 교합면 부위의 법랑모세포에 발현하였고, 1주일 후인 태생 14일에는 백악법랑경계 상방의 치관인접면 법랑모세포에서 발현되었다. 이에 반해 Runx2-typeII는 법랑모세포에서 발현하지 않았다. 또한 태생 21일에서는 두 가지 이성질체가 모두 하악골에서 발현을 보였다 이런 결과를 종합해볼 때, Runx2-full length는 치아의 맹출과 연관이 있으며, 법랑모세포의 분화 및 이로 인한 법랑질형성에 영향을 주지만 Runx2-typeII는 하악골의 형성에만 영향을 미치는 것으로 사료된다.