• 한국발생생물학회지:발생과생식
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• 제13권4호
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• pp.249-256
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• 2009

구조적으로 estrogen 수용체(estrogen receptor, ER)와 유사한 estrogen receptor-related receptor(ERR)는 포유동물에서 배발생 후기에 외배엽 형성과 관련되어 있다고 알려진 고아핵수용체(orphan nuclear receptor)이다. ERR은 ER과 DNA binding domain의 보존성은 유사하지만, ligand 결합 및 전사 활성은 다르다. 포유동물의 ERR에 관한 연구에 비하여 해양 무척추동물의 ERR에 대한 기능 연구는 매우 부족하다. 본 연구에서는 우리나라 동해안에 주로 서식하는 둥근성게(Strongylocentrotus nudus) ERR의 초기 발생기 유전자 발현 변화와 전사 활성 기능을 조사하기 위해 먼저 polymerase chain reaction(PCR)을 이용하여 cDNA를 동정하였다. 둥근성게 ERR은 S. purpuratus와 91%의 높은 상동성을 보였으며, 계통수 분석을 통해 무척추동물 ERR의 clade에 포함되는 것을 알았다. 둥근성게 배발생 시기에 ERR 유전자 발현을 알아보기 위하여 real-time PCR을 실시한 결과, 4~64세포기와 유생기에 mRNA level이 높은 경향을 나타내었다. 또한 호르몬 및 co-regulator에 의한 둥근성게 ERR의 전사 활성을 조사한 결과, 호르몬에 의한 특이성은 확인되지 않았지만, peroxisome proliferator activated receptor-(PPAR) $\gamma$ coactivator $1\alpha$(PGC-$1\alpha$)가 둥근성게 ERR의 coactivator임을 입증할 수 있었다. 이 연구 결과는 향후 새로운 ligand 발굴과 coregulator와 의 상호작용 연구에 도움이 될 것으로 사료된다.

• Clinical and Experimental Reproductive Medicine
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• 제37권3호
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• pp.181-189
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• 2010

태반 (placenta)은 임신기간 동안에만 존재하는 태아유래 일시적인 기관으로, 모체와 태아간의 정확한 조절 기전을 통해 태아의 발달을 수행하는 중요한 기관이다. 영양막세포 (trophoblast)는 임신 초기 빠른 분열 및 분화 과정을 거쳐 태반을 형성하는 주요 세포이다. 영양막세포의 역할은 초기 배아 착상 시기부터 40주간의 임신기간 동안 태반의 형성 과정에서 다양하게 변화된다. 착상은 모체 자궁내막층으로의 포배의 가장 밖에 존재하는 분화된 영양막세포(예, 합포영양막세포)의 침윤에 의해 이루어진다. 또한, 영양막세포은 임신기간 동안 배아의 성숙과 발달에 필요한 영양분과 노폐물 등을 모체와 태아 양방향으로 적절하게 전달할 뿐 아니라 태반 내에서 침윤과 다양한 물질들의 합성 혹은 분비에 관련된 대사작용에 관여한다. 이 기간 동안 영양막세포의 기능 이상은 태아의 선천적인 기형뿐 아니라 자간전증 등을 포함하는 다양한 산과질환을 유발하기도 한다. 그러므로, 영양막세포는 태반과 태아의 발달에 결정적인 요인으로 작용한다. 본 고찰에서는 다양한 영양막세포들의 기능을 이해하기 위해 분류 및 그 종류별 특징 등을 살펴보고, 착상 단계와 태반 발달에 따른 영양막세포의 고유한 역할에 대해 알아보고 향후 활용될 수 있는 연구 분야에 대해 알아보고자 한다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.339-339
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• 1994

It has been reported that Indole-3-carbinol (I3C), a naturally occurring compound In cruclferous vegetables, exerts anticarcinogenic activity In several organs In rodents. The modifying effects of I3C were therefore assessed uging a rat multi-organ carcinogenesis model. A total of 100 male Sprague-Dawley rats were divided Into 3 groups. Animals of groups 1 and 2 were sequentially treated with diethylnitrosamine (DEN; 100 mg/kg b.w., i.p.), N-methylnitrosourea (NNU; 20 mg/kg b.w., 4 times for 2 weeks, i.p), and dihydroxy-di-N-propylnitrosauine (DHPN; 0.1% In d.w. for 2 weeks) for 4 weeks (DMD treatment). Animals of groups 1 and 3 were given the diet of 0.25% I3C for 20 weeks after DMD initiation and then were given basal diet for 28 weeks. All animals were sacrificed at week 24 and 52, respectively. I3C has been clearly demonstrated promoting effects on the development of glutathione S-transferase placental form (GST-P) positive hepatic foci at 24 weeks of the experiment. And I3C also exerted promoting potential In the hepatocellular adenoma (4/14; 29%) and the adenoma (7/14; 50%) of the thyroid gland at 52 weeks of the experiment. Therefore, I3C may promote hepatocarcinogenesis and thyroid tumorigenesis in the rat multi-organ carcinogenesis model.

• Reproductive and Developmental Biology
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• 제31권4호
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• pp.253-260
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• 2007

To examine the differential protein expression pattern in the 11.5 day post-coitus (dpc) and 18.5 dpc placenta of mouse, we have used the global proteomics approach by 2-D gel electrophoresis (2-DE) and MALDI-TOF-MS. The differential protein patterns of 3 placentae at the 11.5 dpc and 18.5 dpc from nature mating mice were analyzed. Proteins within isoelectric point range of $3.0{\sim}10.0$, separately were analyzed in 2DE with 3 replications of each sample. A total of approximately 1,600 spots were detected in placental 2-D gel stained with Coomassie-blue. In the comparison of 11.5 dpc and 18.5 dpc placentae, a total of 108 spots were identified as differentially expressed proteins, of which 51 spots were up-regulated proteins such as alpha-fetoprotein, mKIAA0635 protein and transferrin, annexin A5, while 48 spots were down-regulated proteins such as Pre-B-cell colony-enhancing factor l(PBEF), aldolase 1, A isoform, while 4 spots were 11.5 dpc specific proteins such as chaperonin and Acidic ribosomal phosphoprotein P0, while 3 spots were 18.5 dpc specific proteins such as aldo-keto reductase family 1, member B7 and CAST1/ERC2 splicing variant-1. Most identified proteins in this analysis appeared to be related with catabolism, cell growth, metabolism and regulation. Our results revealed composite profiles of key proteins involved in mouse placenta during pregnancy.

• Asian-Australasian Journal of Animal Sciences
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• 제20권10호
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• pp.1485-1489
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• 2007

Achaete-scute like 2 (ASCL2) gene encodes a member of the basic helix-loop-helix transcription factor which is essential for the maintenance of proliferating trophoblasts during placental development. ASCL2 gene preferentially expresses the maternal allele in the mouse. However, it escapes genomic imprinting in the human. In this study, the complete open reading frame consisting of 193 amino acids of ASCL2 gene was obtained. Sequence analysis indicated that a C-G mutation existed in the 3' region between Meishan and Large White pigs. The polymorphism was used to determine the monoallelic or biallelic expression with RT-PCR-RFLP in pigs of Large $White{\times}Meishan$ $F_1$ hybrids. Imprinting analysis indicated that the ASCL2 gene expression was biallelic in all the tested tissues (heart, liver, spleen, lung, kidney, stomach, small intestine, skeletal muscle, fat, uterus, ovary and pituitary). PCR-RFLP was used to detect the polymorphism in 270 pigs of the "$Large\;White{\times}Meishan$" $F_2$ resource population. The statistical results showed highly significant associations of the genotypes and fat meat percentage (FMP), lean meat percentage (LMP) and ratio of lean to fat (RLF) (p<0.01), and significant associations of the genotypes and loin eye area (LEA) and internal fat rate (IFR) (p<0.05).

• Reproductive and Developmental Biology
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• 제33권1호
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• pp.41-48
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• 2009

Placenta is the main nutrition source for the fetus during pregnancy. Thus, it has a pivotal function in the pregnant process. Many functions of the placenta have been elucidated. An abnormal placenta is associated with a high rate of pregnancy failure in somatic cloned bovine. Differentially expressed genes (DEGs) were examined in a comparison between normal and cloned bovine placenta using annealing control primer (ACP)-based GeneFishing PCR. Using 120 ACPs, nearly 80 genes were identified and the fragments of 42 DEGs were sequenced. 38 of these genes were known genes and four were unknown. To determine the DEGs result, six target clones expressing on one-side of a normal and a clone placenta were selected. Through an analysis of the target genes using the real-time PCR, the expressing pattern was found to be somewhat different from the DEGs. Additionally, several genes appeared with the same expression pattern. Taken together, this suggests that the target genes would be essential for research into what influences the placental formative mechanisms during fetal development.

• Asian-Australasian Journal of Animal Sciences
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• 제25권1호
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• pp.1-16
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• 2012

Reproduction in ruminant species is a highly complex biological process requiring a dialogue between the developing conceptus (embryo-fetus and associated placental membranes) and maternal uterus which must be established during the peri-implantation period for pregnancy recognition signaling and regulation of gene expression by uterine epithelial and stromal cells. The uterus provide a microenvironment in which molecules secreted by uterine epithelia and transported into the uterine lumen represent histotroph, also known as the secretome, that are required for growth and development of the conceptus and receptivity of the uterus to implantation by the elongating conceptus. Pregnancy recognition signaling as related to sustaining the functional lifespan of the corpora lutea, is required to sustain the functional life-span of corpora lutea for production of progesterone which is essential for uterine functions supportive of implantation and placentation required for successful outcomes of pregnancy. It is within the peri-implantation period that most embryonic deaths occur in ruminants due to deficiencies attributed to uterine functions or failure of the conceptus to develop appropriately, signal pregnancy recognition and/or undergo implantation and placentation. The endocrine status of the pregnant ruminant and her nutritional status are critical for successful establishment and maintenance of pregnancy. The challenge is to understand the complexity of key mechanisms that are characteristic of successful reproduction in humans and animals and to use that knowledge to enhance fertility and reproductive health of ruminant species in livestock enterprises.

• Toxicological Research
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• 제29권1호
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• pp.27-34
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• 2013

This study was conducted to investigate the potential embryo-fetal toxicity and toxicokinetics of the antimalarial agent artesunate (ARTS) in Sprague-Dawley rats. Pregnant rats were administered ARTS daily from gestational day 6~15 via oral gavage, at test doses of 0, 2, 4, or 8 mg/kg (22 females per group). The fetuses were examined for external, visceral, and skeletal abnormalities on gestational day 20. With regard to the dams, there were no deaths, treatment-related clinical signs, changes in body weight, or food intake in any of the treatment groups. There were no treatment-related gross findings at necropsy in any treatment group. In the 8 mg/kg group, there was a decrease in gravid uterine weight and in the weight of female fetuses. There was also an increase in fetal deaths (primarily late resorptions) and an increase in post-implantation losses (37%) at 8 mg/kg. An increase in the incidence of visceral and skeletal variations at 4 and 8 mg/kg was observed. These defects included minor changes in the appearance of the kidney and thymus, as well as absent ribs or thoracic vertebrae. Toxicokinetics were assessed in a parallel study, using 4 mated females per group. Using liquid chromatography-mass spectrometry (LC-MS) analysis, the concentration of ARTS and its metabolite dihydroartemisinin (DHA) were quantified in plasma from rats on gestational days 5, 6, 10, and 15. Amniotic fluid was assayed for ARTS and DHA on gestational day 15. There was evidence of rapid conversion of ARTS to the metabolite DHA in maternal plasma, since ARTS could not be consistently detected in plasma at the three doses tested. ARTS and DHA were not detected in amniotic fluid at gestational day 15, indicating limited placental transfer of the two agents. The embryo-fetal no-observable-adverse-effect level (NOAEL) of the test item was considered to be 8 mg/kg/day for dams, and 2 mg/kg/day for embryo-fetal development.

• 한국동물생명공학회지
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• 제37권4호
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• pp.218-225
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• 2022

High levels of proinflammatory cytokines have been observed in obese pregnancies. Obesity during pregnancy may increase the risk of various pregnancyrelated complications, with pathogenesis resulting from excessive inflammation. Palmitic acid (PA) is a saturated fatty acid that circulates in high levels in obese women. In our previous study, we found that PA inhibited the proliferation of trophoblasts developing into the placenta, induced apoptosis, and regulated the number of cleaved halves derived from transfer RNAs (tRNAs). However, it is not known how the expression of tRNA-derived stress-induced RNAs (tiRNAs) changes in response to PA treatment at concentrations that induce inflammation in human trophoblasts. We selected concentrations that did not affect cell viability after dose-dependent treatment of HTR8/SVneo cells, a human trophoblast cell line. PA (200 μM) did not affect the expression of apoptotic proteins in HTR8/SVneo cells. PA significantly increased the expression of inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α. In addition, 200 μM PA significantly increased the expression of tiRNAs compared to 800 μM PA treatment. These results suggest that PA impairs placental development during early pregnancy by inducing an inflammatory response in human trophoblasts. In addition, this study provides a basis for further research on the association between PA-induced inflammation and tiRNA generation.

• 한국발생생물학회지:발생과생식
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• 제27권4호
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• pp.195-203
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• 2023

Exposure to environmental chemicals, including endocrine-disrupting chemicals, during the gestational period can have profound adverse effects on several organs in offspring. Bisphenol A (BPA) can infiltrate the human body through food and drinks, and its metabolites can cross both the placental and the blood-brain barriers. In this study, we investigate the effect of gestational exposure to BPA on epigenetic, biochemical, and histological modifications in the uterine tissues of F1 adult offspring rats. Pregnant rats were exposed to BPA from gestational day 8-15, and changes in global DNA methylation in uterine tissues obtained from adult offspring born to the exposed mothers were analyzed. Global DNA methylation analysis revealed that gestational exposure to BPA resulted in DNA hypomethylation in the uterus. Progesterone receptor (PR) protein expression in uterine tissues was monitored using western blot analysis, which revealed that the PR protein content was considerably higher in all BPA-exposed groups than in the control. Immunohistochemical examination for the PR revealed that intense PR-positive cells were more frequently observed in the BPA-exposed group than in the control group. To date, the evidence that the upregulation of PRs observed in the present study was caused by the non-methylation of specific PR promoter regions is lacking. Conclusively, these results indicate that exposure to BPA during gestation induces epigenetic alterations in the uteri of adult female offspring. We speculate that the global DNA hypomethylation and upregulation of the PR observed simultaneously in this study might be associated with the uterus.