• Toxicological Research
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• v.26 no.4
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• pp.275-283
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• 2010

Placenta transfer study in non-human primate (NHP) is one of the crucial components in the assessment of developmental toxicity because of the similarity between NHP and humans. To establish the method to determine placenta transfer in non-human primate, toxicokinetics of valproic acid (VPA), a drug used to treat epilepsy in pregnant women, were determined in pregnant cynomolgus monkeys. After mating, pregnancy-proven females were daily administered with VPA at dose levels of 0, 20, 60 and 180 mg/kg by oral route during the organogenesis period from gestation day (GD) 20 to 50. Concentrations of VPA and its metabolite, 4-ene-VPA, in maternal plasma on GDs 20 and 50, and concentrations of VPA and 4-ene-VPA in placenta, amniotic fluid and fetus on GD 50 were analyzed using LC/MS/MS. Following single oral administration of VPA to pregnant monkeys, concentrations of VPA and 4-ene-VPA were generally quantifiable in the plasma from all treatment groups up to 4-24 hours post-dose, demonstrating that VPA was absorbed and the monkeys were systemically exposed to VPA and 4-ene-VPA. After repeated administration of VPA to the monkeys, VPA was detected in amniotic fluid, placenta and fetus from all treatment groups, demonstrating that VPA was transferred via placenta and the fetus was exposed to VPA, and the exposures were increased with increasing dose. Concentrations of 4-ene-VPA in amniotic fluid and fetus were below the limit of quantification, but small amount of 4-ene-VPA was detected in placenta. In conclusion, pregnant monkeys were exposed to VPA and 4-ene-VPA after oral administration of VPA at dose levels of 20, 60 and 180 mg/kg during the organogenesis period. VPA was transferred via placenta and the fetus was exposed to VPA with dose-dependent exposure. The metabolite, 4-ene VPA, was not detected in both amniotic fluid and fetus, but small amount of 4-ene-VPA was detected in placenta. These results demonstrated that proper procedures to investigate placenta transfer in NHP, such as mating and diagnosis of pregnancy via examining gestational sac with ultrasonography, collection of amniotic fluid, placenta and fetus after Caesarean section followed by adequate bioanalysis and toxicokinetic analysis, were established in this study using cynomolugus monkeys.

• Toxicological Research
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• v.29 no.1
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• pp.53-60
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• 2013

Studies on milk transfer of drugs in non-human primates (NHPs) are among the crucial components in the assessment of peri- and postnatal toxicity because of the similarity between NHPs and humans. To evaluate the milk transfer of valproic acid (VPA) in NHPs, the toxicokinetics of VPA, an antiepileptic drug, were studied in pregnant cynomolgus monkeys. VPA was administered once daily to pregnant cynomolgus monkeys at doses of 0, 30, 90, and 270 mg/kg by oral gavage from Day 100 of gestation (GD 100) to Day 31 of lactation (LD 31). Concentrations of VPA and its metabolite, 4-ene-VPA, in the maternal plasma on GD 100, GD 140, and LD 30, and concentrations of VPA and 4-ene-VPA in the offspring plasma and milk on LDs 30 and 31, respectively, were quantified using liquid chromatography tandem mass spectrometry (LC/MS/MS). After administration of a single oral dose of VPA to pregnant monkeys on GD 100, the concentrations of VPA and 4-ene-VPA were generally quantifiable in the plasma of all treatment groups up to 24 hr after administration, which showed that VPA was absorbed and that the monkeys were systemically exposed to VPA and 4-ene-VPA. After administration of multiple doses of VPA to the monkeys, VPA was detected in the pup's plasma and in milk taken on LD 30 and LD 31, respectively, which showed that VPA was transferred via milk, and the pup was exposed to VPA. Further, the concentration of VPA in the milk increased with an increase in the dose. Extremely low concentrations of 4-ene VPA were detected in the milk and in the pup plasma. In conclusion, pregnant monkeys were exposed to VPA and 4-ene-VPA after oral administration of VPA at doses of 30, 90, and 270 mg/kg/day from GD 100 to LD 31. VPA was transferred via milk, and the VPA exposure to the pup increased with an increase in the dose of VPA. The metabolite, 4-ene VPA, was present in extremely low concentrations (< 0.5 ${\mu}g/ml$) in the milk and in the pup plasma. In this study, we established methods to confirm milk transfer in NHPs, such as mating and diagnosis of pregnancy by examining gestational sac with ultrasonography, collection of milk and pup plasma and determination of toxicokinetics, using cynomolgus monkeys.

• Animal cells and systems
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• v.1 no.2
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• pp.337-340
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• 1997

The purpose of this study is to evaluate whether water soluble chitosan, a natural nontoxic chelator, can reduce fetal contamination of radiostrontium in pregnant mice. Various forms of water soluble chitosans (10% or 1% powder, or 1% solution) were given to pregnant mice before or after contamination of 0.005 uCi/B.W(g) Sr-85. Transplacental transfer of Sr-85 to fetus was $6.8{\pm}2.7%$ of injected dose, when Sr-85 was administered at the 20th day of pregnancy. Fetal radioactivity was significantly reduced when mother mice were treated with water soluble chitosan before contamination of Sr-85. Water soluble chitosans of 10% or 1% powder, or 1% solution significantly reduced fetal retention of Sr-85 to $2.3{\pm}0.7%$, $2.7{\pm}0.8%$, and $2.0{\pm}0.9%$, respectively. However, fetal contamination was not reduced, when water soluble chitosans of 10% or 1% powder, or 1% solution were administered after maternal contamination of Sr-85. From these data we can conclude that water soluble chitosan could reduce fetal contamination of radiostrontium in pregnant mice, when given before the pregnant mice were exposed to radiostrontium.

• Journal of Preventive Medicine and Public Health
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• v.13 no.1
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• pp.67-75
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• 1980

Natural increase rate in population is reached to 1.7% in 1975 fron 2.5% in 1966 because of the effect of Govermental Family Planning Program. The average number of present children and ideal children is just the same, 2.4 people, in this investigation. So, I assume that the number of present and ideal children is approaching each other. The rate of unmarried female workers who don't know even one thing about the know ledge of contraception was 23.9%, and especially that of rural women was 31.5% and 41.3% of them has never experienced contraception. 'Boy-preference' presented 60.1% of unmarried female workers and 79.1% of married women. 'Connection of a family line' related to 'Transfer to next generation of a family line' presented 38.0% and 'Trustworthiness' related to 'Leadership of a family' presented 26.0% (total 64.0%). As this point, Ive can find that this rate reveals the traditional sense of patriarchal system in society and family. The rate of women of experienced artificial abortion has been 52.1% and that of women using it as birth control caused by 'Many children' and 'Short brith-interval' 46.6% of women of experienced pregnancy. So, we can see that artificial abortion is a main cause of Maternal Health destruction.

• Proceedings of the KSAR Conference
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• 2004.06a
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• pp.228-228
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• 2004

Interferon-tau (IFN-τ) is the primary agent responsible for maternal recognition of pregnancy in cattle. Bovine embryos begine to express IFN-τ as the blastocyst forms. Pregnancy recognition in ruminants occurs when IFN-τ from the trophoblast prevents the increase of oxytocin receptors, disrupting luteolytic pulses of prostaglandin (PG) F2a by oxytocin. The expression of IFN-τ is strongly associated with the degree of methylation of the CpG islands in promoter region. (omitted)

• Clinical and Experimental Reproductive Medicine
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• v.47 no.2
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• pp.85-93
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• 2020

The implantation process is highly complex and difficult to mimic in vitro, and a reliable experimental model of implantation has yet to be established. Many researchers have used embryo transfer (ET) to assess implantation potential; however, ET with pseudopregnant mice requires expert surgical skills and numerous sacrificial animals. To overcome those economic and ethical problems, several researchers have tried to use outgrowth models to evaluate the implantation potential of embryos. Many previous studies, as well as our experiments, have found significant correlations between blastocyst outgrowth in vitro and implantation in utero by ET. This review proposes the blastocyst outgrowth model as a possible alternative to animal experimentation involving ET in utero. In particular, the outgrowth model might be a cost- and time-effective alternative method to ET for evaluating the effectiveness of culture conditions or treatments. An advanced outgrowth model and further culture of outgrowth embryos could provide a subtle research model of peri- and postimplantation development, excluding maternal effects, and thereby could facilitate progress in assisted reproductive technologies. Recently, we found that outgrowth embryos secreted extracellular vesicles containing specific microRNAs. The function of microRNAs from outgrowth embryos should be elucidated in further researches.

• Journal of the Korean Society of Tobacco Science
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• v.17 no.1
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• pp.41-48
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• 1995

Tobacco mosaic virus (TMV), TMV-common strain, causes severe damage on flue-cured tobacco in Korea. As the results, breeding programs were conducted to transfer the TMV resistance from NC567 to other cultivars. Advantage of F1, hybrid may not lie only in their heterotic value but also in directly combining of valuable dominant traits, e.g. for disease resistance, either in pairs or as groups already assembled in the two parents. A new TMV resistant flue-cured tobacco variety KF114 was developed from a cross as maternal parent MSNC567 and NC82 at the Suwon Experiment Station. KF114 was more vigorous growth characteristics in early stage than that of NC82, standard variety in Korea, and other characters were similar to those of NC82. It os high resistance to TMV, but bacterial wilt(Pseudomonas solanacerum) and black shank (Phytophthora parasitica var. nicotianae) is comparable to NC82. It should adapt well to the flue-cured production area and can reduce premature flowering under unfavorable weather conditions. Yield of KF114 is 1% to 5% higher, and nearly equal in value per KG compared with NC82. This variety, F1 hybrid, met acceptable standards for chemical and physical characteristics of cured leaf and high ranked good smoking taste by panel members in Korea Ginseng and Tobacco Research Institute.

• Journal of Species Research
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• v.8 no.3
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• pp.313-317
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• 2019

Bats influence overall ecosystem health by regulating species diversity and being a major source of zoonotic viruses. Hence, there is a need to elucidate their migration, population structure, and phylogenetic relationship. The complete mitochondrial genome is widely used for studying the genome-level characteristics and phylogenetic relationship of various animals due to its high mutation rate, simple structure, and maternal inheritance. In this study, we determined the complete mitogenome sequence of the bird-like noctule (Nyctalus aviator) by Illumina next-generation sequencing. The sequences obtained were used to reconstruct a phylogenic tree of Vespertilionidae to elucidate the phylogenetic relationship among its members. The mitogenome of N. aviator is 16,863-bp long with a typical vertebrate gene arrangement, consisting of 13 protein-coding genes (PCGs), 22 transfer RNA genes, 2 ribosomal RNA genes, and 1 putative control region. Overall, the nucleotide composition is as follows: 32.3% A, 24.2% C, 14.3% G, and 29.2% T, with a slight AT bias (61.5%). The base composition of the 13 PCGs is as follows: 30.3% A, 13.4% G, 31.0% T, and 25.2% C. The phylogenetic analysis, based on 13 concatenated PCG sequences, infers that N. aviator is closely related to N. noctula with a high bootstrap value (100%).

• Pediatric Infection and Vaccine
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• v.5 no.1
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• pp.121-127
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• 1998

Purposes : This study was performed to evaluate the seropositivities and levels of term pregnant women and their neonates, and the transplacental transfer rate of maternal Epstein-Barr Virus-specific IgG(VCA IgG and EBNA IgG) from term pregnant women to their neonates. Subjects and Methods : During Jan. 1, 1997 to Mar. 31. 1997, we collected the 42 pairs of sera from pregnant women and umbilical cord of their neonates in Korea University Ansan Hospital. The serum levels of VCA IgG and EBNA IgG were measured by the ELISA method. Results : 1) The seropositivities of VCA IgG were 100% in mothers and neonates. There was no statistical difference of mean VCA IgG levels between mothers and neonates. There was significant correlation of VCA IgG levels between maternal sera and neonatal umbilical cord sera(correlation coefficient r=0.5214, P<0.001). 2) The seropositivities of EBNA IgG were 100% in mothers and neonates. There was no significant difference of the mean EBNA IgG levels between mothers and neonates. There was significant correlation of EBNA IgG levels between maternal sera and neonatal umbilical cord sera (correlation coefficient r=0.7244, P<0.001). 3) There was no correlation between VCA IgG and EBNA IgG levels of maternal sera. Conclusion : Seropositivities of EBV CA IgG and EBNA IgG of term-pregnant women and their neonates were 100% and no significant differences of antibody levels were found in two groups. It seems that EBV Antibody levels in Korean mothers and neonates were high enough to protect primary EBV infection during early infancy.

• Journal of Embryo Transfer
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• v.32 no.4
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• pp.287-295
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• 2017

Mitochondrial dysfunction is found in oocytes and transmitted to offspring due to maternal obesity. Treatment of obese mothers with endoplasmic reticulum (ER) stress inhibitors such as salubrinal (SAL) can reverse the mitochondrial dysfunction and result in normal embryonic development. Pig oocytes have also shown ER stress mostly in metaphase II stage. ER stress in oocytes may hinder the in vitro production of pig embryos. This study investigated the effect of ER stress inhibition by SAL treatment during in vitro maturation (IVM) of porcine oocytes at 1, 10, 50 and 100 nM concentrations. Firstly, we tested various concentrations of SAL. SAL at 10 nM showed higher (P < 0.05) developmental competence to the blastocyst stage (55.6%) after parthenogenesis (PA) than control (44.2%) while not different from other concentrations (49.2, 51.6, and 50.8% for 1, 50, and 100 nM, respectively). Secondly, we performed time-dependent treatment at 10 nM of SAL for IVM of oocytes. It revealed that treatment with SAL during 22 to 44 h of IVM significantly improved PA embryonic development to the blastocyst stage compared to control (40.5, 46.3, 51.7 and 60.2% for control, 0 to 22 h, 22 to 44 h and 0 to 44 h of IVM, respectively, P < 0.05). Glutathione (GSH) content is an indicator of cytoplasmic maturation of oocytes. Reactive oxygen species (ROS) have a harmful effect on developmental competence of oocytes. For this, we determined the intraoocyte levels of GSH and ROS after 44 h of IVM. It was found that SAL increased intraoocyte GSH level and also decreased ROS level (P < 0.05). Finally, we performed somatic cell nuclear transfer (SCNT) after treating oocytes with 10 nM SAL during IVM. SAL treatment significantly improved blastocyst formation of SCNT embryos compared to control (39.6% vs. 24.7%, P < 0.05). Our results indicate that treatment of pig oocytes with ER stress inhibitor SAL during IVM improves preimplantation development PA and cloned pig embryos by influencing cytoplasmic maturation in terms of increased GSH content and decreased ROS level in IVM pig oocytes.