• Biomolecules & Therapeutics
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• 제22권1호
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• pp.68-72
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• 2014

When chemotherapy is administered during pregnancy, it is important to consider the fetus chemotherapy exposure, because it may lead to fetal consequences. Paclitaxel has become widely used in the metastatic and adjuvant settings for woman with cancer including breast and ovarian cancer. Therefore, we attempted to clarify the transport mechanisms of paclitaxel through blood-placenta barrier using rat conditionally immortalized syncytiotrophoblast cell lines (TR-TBTs). The uptake of paclitaxel was time- and temperature-dependent. Paclitaxel was eliminated about 50% from the cells within 30 min. The uptake of paclitaxel was saturable with $K_m$ of $168{\mu}M$ and $371{\mu}M$ in TR-TBT 18d-1 and TR-TBT 18d-2, respectively. [$^3H$]Paclitaxel uptake was markedly inhibited by cyclosporine and verapamil, well-known substrates of P-glycoprotein (P-gp) transporter. However, several MRP substrates and organic anions had no effect on [$^3H$]paclitaxel uptake in TR-TBT cells. These results suggest that P-gp may be involved in paclitaxel transport at the placenta. TR-TBT cells expressed mRNA of P-gp. These findings are important for therapy of breast and ovarian cancer of pregnant women, and should be useful data in elucidating teratogenicity of paclitaxel during pregnancy.

• Journal of Pharmaceutical Investigation
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• 제38권5호
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• pp.295-302
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• 2008

In the present study, we examined the changes of uptake and efflux of taurine under various conditions inducing oxidative stress using rat conditionally immortalized syncytiotrophoblast cell line, TR-TBT cell, as blood-placental barrier in vitro model. In addition, we identified the characteristics of taurine transport in TR-TBT cells including general features, besides effect of calcium ion on taurine transport. Taurine uptake showed time, $Na^+$ and $Cl^-$ dependency, and was decreased by PKC activator in TR-TBT cells. Also, calcium free condition decreased taurine uptake and evoked taurine efflux in the cells. Oxidative stress induced the change of taurine transport in TR-TBT cells, but the changes were different depending on the types of stimulation inducing oxidative stress. The taurine uptake was increased by TNF-$\alpha$, LPS and DEM stimulation but decreased by $H_2O_2$ and NO stimulation. Also, the taurine efflux was regulated by TNF-$\alpha$ stimulation. In conclusion, the taurine transport through the blood-placental barrier was regulated in oxidative stress conditions, and these results demonstrated that oxidative stress affected the taurine supplies to fetus and taurine level of fetus.

• Reproductive and Developmental Biology
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• 제30권2호
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• pp.107-113
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• 2006

Development of placenta is a complex process that is critical for the pregnancy and controlled by many factors including cytokines, hormones, growth factors and apoptotic molecules. Recently, it has been shown that progranulin (PGRN) functions in growth of embryo and trophectoderm as well as cell migration. To initiate understanding the role of PGRN in human placental development, we investigated the expression of PGRN mRNA and protein in early and late gestation human placentas, term cytotrophoblast cells and two choriocarcinoma cell lines, JEG-3 and Jar. Reverse transcriptase polymerase chain reaction identified mRNAs derived from the PGRN gene in all samples. Immunoblot analysis showed that PGRN proteins are present in early and late gestation human placentas with decreasing levels over gestation and that PGRN proteins are present in normal and transformed trophoblast cells. Immunohistochemical analysis using paraformaldehyde-fixed tissue sections taken from early and late stages of pregnancy showed that PGRN proteins are present in cytotrophoblast cells, syncytiotrophoblast and extravillous cytotrophoblast cells and that expression pattern of PGRN differed according to the stage of cell differentiation. The results of this study are consistent with the hypothesis that PGRN proteins have critical roles in placental development and suggest that PGRN may function in trophoblast cell growth and differentiation.

• 한국동물번식학회:학술대회논문집
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• 한국동물번식학회 2003년도 학술발표대회 발표논문초록집
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• pp.37-37
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• 2003

본 연구실에서는 체세포복제 수정란 이식우의 분만전후 태아와 모체 및 태반과의 내분비적인 관계를 검토하기 위해 복제수정란 이식우의 분만 전후에 있어서, 혈중progesterone 과 TGF-$\beta$$_1$ 수준을 분석한 결과 정상우의 분만직전과 달리 혈중progesterone 및 TGF-$\beta$$_1$ 농도는 감소되지 않고 높은 수준을 그대로 유지되어 복제수정란이식우의 경우 정상적인 분만 signal이 나타나지 않는 것으로 나타났다. 본 연구는 체세포 복제소 수정란 이식우에 있어서 태반조직의 특성을 정상우의 동일한 시기의 태반과 비교 검토하였으며 분만시기에 있어서 태반의 역할을 검토하였다. 태반은 복제란 이식우 및 정상우 임신우를 술을 실시하여 태반을 채취하여 실험에 공시하였다. 정상우의 임신기간중 혈중 progesterone 농도는 임신초기와 중기에 다소 증가되어 유지되다가 임신말기에는 급격한 progesterone의 감소현상과 더불어 분만이 유기되는 것으로 나타났으나 복제우의 경우 분만예정일 직전까지 progesterone의 급격한 감소는 일어나지 않고 높은 농도로 유지되는 현상을 보였다. 이때 제왕절제 수술중 제대근방에 있는 태반궁부를 적출하여 중량을 측정한 결과 정상우의 궁부에 비해 유의적으로 무거웠으며, 이것은 태아의 중량과 정의 상관관계가 있음이 확인되었으며 태아 및 궁부의 중량이 무거울수록 분만 전후의 태아사망율이 높은 것으로 나타났다 이때의 궁부를 조직학적으로 검토한 결과, 복제우의 태반궁부는 정상우의 궁부에 비해 cytotrophoblast 및 syncytiotrophoblast가 적었으며 치밀하지 못한 형태를 확인할 수 있었다. 이때의 태반조직를 이용하여 세포질을 추출하여 단백질양상을 검토한 결과, 정상태반에 비해 복제태반은분자량 90kd, 65kd 및 18kd의 특이단백질이 존재하고 있음을 확인할 수 있었으며 이들 단백질을 HPLC system에 의해 분리한 결과 fraction 2와 3에서 특이한 단백질을 분리하였다. 이와 같이, 복제우의 태반에는 정상적인 임신과 분만을 비롯하여 복제송아지의 생존에 중요한 인자가 관여하고 있을 확인할 수 있었다.

• Reproductive and Developmental Biology
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• 제42권2호
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• pp.7-12
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• 2018

In this review, we have tried to summarize the evidence and molecular characterization indicating that $20{\alpha}$-hydroxysteroid dehydrogenase ($20{\alpha}$-HSD) is a group of the aldo-keto reductase (AKR) family, and it plays roles in the modulation and regulation of steroid hormones. This enzyme plays a critical role in the regulation of luteal function in female mammals. We have studied the molecular expression and regulation of $20{\alpha}$-HSD in cows, pigs, deer, and monkeys. The specific antibody against bovine $20{\alpha}$-HSD was generated in a rabbit immunized with the purified recombinant protein. The mRNA expression levels increased gradually throughout the estrous cycle, the highest being in the corpus luteum (CL) 1 stage. The mRNA was also specifically detected in the placental and ovarian tissues during pregnancy. The $20{\alpha}$-HSD protein was intensively localized in the large luteal cells and placental cytotrophoblast villus, glandular epithelial cells of the endometrium, syncytiotrophoblast of the placenta, the isthmus cells of the oviduct, and the basal part of the primary chorionic villi and chorionic stem villus of the placenta and large luteal cells of the CL in many mammalian species. Further studies are needed to determine the functional significance of the $20{\alpha}$-HSD molecule during ovulation, pregnancy, and parturition. This article will review how fundamental information of these enzymes can be exploited for a better understanding of the reproductive organs during ovulation and pregnancy.

• Parasites, Hosts and Diseases
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• 제53권2호
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• pp.189-196
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• 2015

The sequestration of infected erythrocytes in the placenta can activate the syncytiotrophoblast to release cytokines that affect the micro-environment and influence the delivery of nutrients and oxygen to fetus. The high level of IL-10 has been reported in the intervillous space and could prevent the pathological effects. There is still no data of Th17 involvement in the pathogenesis of placental malaria. This study was conducted to reveal the influence of placental IL-17 and IL-10 levels on fetal weights in malaria placenta. Seventeen pregnant BALB/C mice were divided into control (8 pregnant mice) and treatment group (9 pregnant mice infected by Plasmodium berghei). Placental specimens stained with hematoxylin and eosin were examined to determine the level of cytoadherence by counting the infected erythrocytes in the intervillous space of placenta. Levels of IL-17 and IL-10 in the placenta were measured using ELISA. All fetuses were weighed by analytical balance. Statistical analysis using Structural Equation Modeling showed that cytoadherence caused an increased level of placental IL-17 and a decreased level of placental IL-10. Cytoadherence also caused low fetal weight. The increased level of placental IL-17 caused low fetal weight, and interestingly low fetal weight was caused by a decrease of placental IL-10. It can be concluded that low fetal weight in placental malaria is directly caused by sequestration of the parasites and indirectly by the local imbalance of IL-17 and IL-10 levels.

• 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.