• Asian-Australasian Journal of Animal Sciences
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• v.22 no.11
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• pp.1495-1503
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• 2009

This experiment was conducted to determine the effect of dietary supplementation with BCAA (branched-chain amino acids: leucine, isoleucine and valine) on improving the growth of rats in a malnutritional IUGR (Intrauterine Growth Retardation) model, which was established by feeding restriction. In the experimental treatment, rats were fed purified diets supplemented with BCAA (mixed) during the whole gestation period, while arginine and alanine supplementation were set as the positive and negative control group, respectively. The results showed that, compared to the effect of alanine, BCAA reversed IUGR by increasing the fetus weights by 18.4% and placental weights by 18.0% while fetal numbers were statistically increased. Analysis of gene and protein expression revealed that BCAA treatment increased embryonic liver IGF-I expression; the uterus expressed higher levels of estrogen receptor-$\alpha$ (ER-$\alpha$) and progesterone receptor (PR), and the placenta expressed higher levels of IGF-II. Amino acid analysis of dam plasma revealed that BCAA supplementation effectively enhanced the plasma BCAA levels caused by the feed restriction. BCAA also enhanced the embryonic liver gluconeogenesis by augmenting the expression of two key enzymes, namely fructose-1,6-biphosphatase (FBP) and phosphoenolpyruvate carboxykinase (PEPCK). In conclusion, supplementation of BCAA increased litter size, embryonic weight and litter embryonic weight by improving the dam uterus and placental functions as well as increasing gluconeogenesis in the embryonic liver, which further provided energy to enhance the embryonic growth.

• Asian-Australasian Journal of Animal Sciences
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• v.25 no.8
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• pp.1096-1101
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• 2012

Intrauterine growth retardation (IUGR) leads to the dysfunction in digestive system, as well as the alteration in the expression of some functional proteins. Heat shock protein 70 (Hsp70) could be induced by various stress factors, but whether Hsp70 expression is changed in neonatal IUGR infants has not been demonstrated. This study was conducted to explore the expression of Hsp70 in the liver by using the IUGR piglet model. Liver and plasma samples were obtained from IUGR and normal birth weight (NBW) piglets at birth. The neonatal IUGR piglets had significantly lower liver weight than their counterparts. The activities of aspartate aminotransferase and alanine aminotransferase in serum were enhanced significantly in IUGR indicating liver dysfunction. The activities of superoxide dismutase (p<0.01), glutathione peroxidase (p<0.01) and catalase (p>0.05) were lower and the level of malondialdehybe was higher (p<0.05) in IUGR liver compared with in NBW. According to the results of histological tests, fatty hepatic infiltrates and cytoplasmic vacuolization were present in the liver of IUGR piglets, but not in NBW liver. The expression of Hsp70 protein was significantly higher (p<0.05) in IUGR piglet liver than in NBW. Similar to where the hepatic injuries were observed, location of Hsp70 was mostly in the midzonal hepatic lobule indicating that oxidative stress might be responsible for the increased expression of Hsp70.

• Journal of Genetic Medicine
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• v.17 no.2
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• pp.83-88
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• 2020

Silver-Russell syndrome (SRS) is a rare genetic disorder characterized by intrauterine growth restriction, poor postnatal growth, relative macrocephaly, a triangular face, body asymmetry, and feeding difficulties. It is primarily diagnosed according to a clinical scoring system; however, the clinical diagnosis is confirmed with molecular testing, and the disease is stratified into the specific molecular subtypes. SRS is a genetically heterogeneous condition. The major molecular changes are hypomethylation of imprinting control region 1 in 11p15.5 and maternal uniparental disomy of chromosome 7 (UPD(7)mat). Therefore, first-line molecular testing should include methylation-specific approaches for these regions. Here, we report an extremely low birth weight (ELBW) infant with intrauterine growth retardation, postnatal growth retardation, and dysmorphic facial appearance-characteristics consistent with the clinical diagnostic criteria of SRS. Methylation-specific molecular genetic analysis revealed UPD(7)mat, while the loss of heterozygosity was not detected on chromosomal microarray analysis. We present a case of SRS with suspected uniparental heterodisomy of chromosome 7 in an ELBW infant.

• Clinical and Experimental Pediatrics
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• v.49 no.9
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• pp.966-971
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• 2006

Purpose : 'Programming' describes the process that stimulus at a critical period of development has lifelong effects. The fact that low birth weight links to the risk of elevated blood pressures in adult life is well known. This study aims to examine whether this link is evident in the newborn by investigating the relationship of the intrauterine growth indices and neonatal blood pressure(BP). Methods : We studied 127 neonates who were born at Ewha Womans' Hospital and their mothers enrolled our cohort study during pregnancy. Data on the mothers and details of the birth records were tracked and collected from medical charts. Neonatal BP was measured within 24 hours after birth. Results : Neonatal SBP was positively correlated to intrauterine growth indices; birth weight(BW)(r=0.4), head circumference(HC)(r=0.4), and birth height(r=0.3). However, an inverse relationship existed, between HC/BW ratio and neonatal SBP(r=-0.4). After adjusting for the baby's sex, maternal BP, and gestational age, neonatal SBP still associated with intrauterine growth indices. SBP was 7 mmHg higher in the highest BW group(${\geq}90percentiles$) compared to the lowest group(<10 percentiles). On the other hand, SBP was 17 mmHg lower in the highest HC/BW group(${\geq}90percentiles$) compared in the lowest group(<10 percentiles). Conclusion : This study could not find the evidence that intrauterine growth retardation affect on elevated neonatal BP. It suggests that the initiating events of BP programming may occur during postnatal growth period. To identify the critical starting period that intrauterine growth retardation leads to elevated BP, a study tracking BP changes from birth to childhood is required.

• Journal of radiological science and technology
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• v.14 no.2
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• pp.37-44
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• 1991

The combined effect of radiation and ultrasound has been studied in mouse embryos. Radiation and/or ultrasound were adminstered to ICR mice on day 8 of gestation. Intrauterine death, gross malformation, and fetal body weight were selected as indicators of effects. Does of whole-body ${\gamma}-irradiation$ were 0.5 to 2.5 Gy and those of ultrasound were $0.5\;W/cm^2$ to $3\;W/cm^2$. Intrautrine mortality increased with increasing radiation dose ; this trend was more remarkable in combination with ultrasound. Gross malformations such as exencephaly and anophthalmia/microphthalmia appeared frequently in the fetuses treated with both radiation and ultrasound. Decreased fetal weight was observed even in mice treated with 1.5 Gy of radiation or $1\;W/cm^2$ of ultrasound. There was a linear relationship between dose and reduction of fetal weight. The fetal weight was sensitive, precise and easy-to-handle indicator for the effects of growth retardation. Intrauterine mortality and frequencies of exencephaly and anophthalmia/microphthalmia were higher than the sum of those induced by radiation and by ultrasound. The results indicatied that the combined action of radiation and ultrasound on intrauterine death and malformations was synergistic.

• Clinical and Experimental Pediatrics
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• v.61 no.4
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• pp.114-120
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• 2018

Purpose: Routine screening for toxoplasmosis, rubella, cytomegalovirus (CMV), and herpes simplex virus (TORCH) in intrauterine growth restriction (IUGR) and small for gestational age (SGA) neonates has become a common practice. However, the incidence of TORCH varies across countries, and the cost of TORCH testing may be disadvantageous compared to disease-specific screening. To evaluate the efficacy of TORCH screening, the medical charts of IUGR or SGA neonates born in a single institution in Bucheon, Korea from 2011 to 2015 were reviewed. Methods: The clinical data of the 126 IUGR or SGA neonates were gathered, including gestational age, Apgar scores, neonatal sonographic findings, chromosome study, morbidities, developmental follow-up, and growth catch-up. Maternal factors including underlying maternal disease and fetal sonography were collected, and placental findings were recorded when available. TORCH screening was done using serum IgM, CMV urine culture, quantification of CMV DNA with real-time polymerase chain reaction, and rapid plasma reagin qualitative test for syphilis. Tests were repeated only for those with positive results. Results: Of the 119 TORCH screenings, only one was positive for toxoplasmosis IgM. This result was deemed false positive due to negative IgM on repeated testing and the absence of clinical symptoms. Conclusion: Considering the incidence and risk of TORCH in Korea, the financial burden of TORCH screening, and the single positive TORCH finding in our study, we suggest disease-specific screening based on maternal history and the clinical symptoms of the neonate. Regarding CMV, which may present asymptomatically, universal screening may be appropriate upon cost-benefit analysis.

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.3
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• pp.343-348
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• 2013

This experiment was conducted to evaluate the development of T cells in intrauterine growth retarded (IUGR) piglets at different gestational stages, and tentatively explore the relationship between T cells development and the Notch signaling pathway. A total of 18 crossbred (Landrace${\times}$Large white) primiparous sows were mated at similar weights and estruses and euthanized at d 60, 90 and 110 of gestation with six replicates for each time point. One IUGR and one normal fetus were picked from each litter. The T-cell subsets, mRNA expression of Delta-like1, Delta-like4, Jagged1, and Notch2 genes in the thymus were investigated. Compared to normal piglets, $CD3^+CD4^-CD8^+$ cells in IUGR fetuses at d 90 was 0.13% lower (p<0.05). At d 110 of gestation $CD8^+$ T cells in IUGR fetuses was 0.19% lower (p<0.05). The percentage of $CD8^+$ T cells was 3.14% lower (p<0.05) of the total T cells in IUGR pigs at d 60. The abundance of Notch2 and Delta-like4 mRNA at d 110 was 20.93% higher and 0.77% (p<0.05) lower, and Delta-like1 mRNA at d 90 was 0.19% (p<0.05) higher compared to normal pigs. These results suggested that normal fetuses had a greater proportion of T-cell subsets at earlier gestation periods, and the Notch signaling pathway was likely partially responsible for these differences to some degree.

• Journal of Embryo Transfer
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• v.12 no.3
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• pp.229-246
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• 1997

Implantation is a most important biological process during pregnancy whereby conceptus establishes its survival as well as maintenance of pregnancy. During the periimplantation period, both uterine endometriurn and conceptus synthesize and secrete a host of growth factors and cytokines which mediate the actions of estrogen and /or progesterone and also exert their steroid-independent actions. Growth factors expressed by the materno-conceptal unit en masse have important roles in cell migration, stimulation or inhibition of cell proliferation, cellular differentiation, maintenance of pregnancy and materno-conceptal communications in an autorcrine /paracrine manner. The present review focuses on the role of the intrauterine IGF system during periimplantation conceptus development. The IGF system comprises of IGF- I and IGF- II ligands, types I and II IGF receptors and six or more IGF-binding proteins(IGFBPs). IGFs and IGFBPs are expressed and secreted by uterine endometrium with tissue, pregnancy stage and species specificities under the influence of estrogen, progesterone and other growth factor(s). Conceptus also synthesizes components of the IGF system beginning from a period between 2-cell and blastocyst stages. Maternal IGFs are utilized by both maternal and conceptal tissues; conceptus-derived growth factors are believed to be taken up primarily by conceptus. IGFs enhance the development of both maternal and conceptal compartments in a wide range of biological processes. They stimulate proliferation and differentiation of endometrial cells and placental precursor cells including decidual transformation from stromal cells, placental formation and the synthesis of some steroid and protein hormones by differentiated endometrial cells or placenta. It is also well-documented in a number of experimental settings that both IGFs stimulate preimplantation embryo development. In slight contrast to these, prenatal mice carrying a null mutation of IGF and /or IGF receptor gene do not exhibit any apparent growth retardation until after implantation. Reason (s) for this discrepancy between the knock-out result and the in vitro ones, however, is not known. IGFBPs, in general, are believed to inhibit IGF action within the materno-conceptal unit, thereby allowing endometrial stromal cell differentiation as well as dampening ex cessive placental invasion into maternal tissue. There is evidence, however, indicating that IGFBP can enhance IGF action depending on environrnental conditions perhaps by directioning IGF ligand to the target cell. There is also a third possibility that certain IGFBPs and their proteolytic fragments may have their own biological activities independent of the IGF. In addition to IGFBPs, IGFBP proteases including those found within the uterine tissue or lumen are thought to enhance IGF bioavailability by degrading their substrates without affecting their bound ligand. In this regard, preliminary results in early pregnant pigs suggest that a partially characterized IGFBP protease activity in uterine luminal fluid enhances intrauterine IGF bioavailability during conceptus morphological development. In summary, a number of in vitro results indicate that IGFs stimulates the development of the rnaterno-conceptal unit during the periimplantation period. IGFBPs appear to inhibit IGF action by sequestering their ligands, whereas IGFBP proteases are thought to enhance intrauterine bioavailability of IGFs. Much is remaining to be clarified, however, regarding the roles of the individual IGF system components. These include in vivo evidence for the role of IGFs in early conceptus development, identification of IGF-regulated genes and their functions, specific roles for individual IGFBPs, identification and characterization of IGFBP proteases. The intrauterine IGF club house thus will be paying a lot of attention to forthcoming results in above and other areas, with its door wide-open!

• Asian-Australasian Journal of Animal Sciences
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• v.31 no.5
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• pp.686-695
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• 2018

Objective: The objective of this study was to investigate the effects of dietary choline supplementation on hepatic lipid metabolism and gene expression in finishing pigs with intrauterine growth retardation (IUGR). Methods: Using a $2{\times}2$ factorial design, eight normal birth weight (NBW) and eight IUGR weaned pigs were fed either a basal diet (NBW pigs fed a basal diet, NC; IUGR pigs fed a basal diet, IC) or a diet supplemented with two times more choline than the basal diet (NBW pigs fed a high-choline diet, NH; IUGR pigs fed a high-choline diet, IH) until 200 d of age. Results: The results showed that the IUGR pigs had reduced body weight compared with the NBW pigs (p<0.05 from birth to d 120; p = 0.07 from d 120 to 200). Increased (p<0.05) free fatty acid (FFA) and triglyceride levels were observed in the IUGR pigs compared with the NBW pigs. Choline supplementation decreased (p<0.05) the levels of FFAs and triglycerides in the serum of the pigs. The activities of malate dehydrogenase and glucose 6-phosphate dehydrogenase were both increased (p<0.05) in the livers of the IUGR pigs. Choline supplementation decreased (p<0.05) malate dehydrogenase activity in the liver of the pigs. Gene expression of fatty acid synthase (FAS) was higher (p<0.05) in the IC group than in the other groups, and choline supplementation decreased (p<0.05) FAS and acetyl-CoA carboxylase ${\alpha}$ expression in the livers of the IUGR pigs. The expression of carnitine palmitoyl transferase 1A (CPT1A) was lower (p<0.05) in the IC group than in the other groups, and choline supplementation increased (p<0.05) the expression of CPT1A in the liver of the IUGR pigs and decreased (p<0.01) the expression of hormone-sensitive lipase in both types of pigs. The gene expression of phosphatidylethanolamine N-methyltransferase (PEMT) was higher (p<0.05) in the IC group than in the other groups, and choline supplementation significantly reduced (p<0.05) PEMT expression in the liver of the IUGR pigs. Conclusion: In conclusion, the lipid metabolism was abnormal in IUGR pigs, but the IUGR pigs consuming twice the normal level of choline had improved circulating lipid parameters, which could be related to the decreased activity of nicotinamide adenine dinucleotide phosphate-generating enzymes or the altered expressions of lipid metabolism-related genes.

• Journal of the korean academy of Pediatric Dentistry
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• v.29 no.1
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• pp.51-56
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• 2002

Russell-Silver syndrome is a type of intrauterine growth retardation, characterized by short stature noted at birth, hemiatrophy or asymmetry, variation in sexual development and other abnormalities, including cafe-aulait pigmentation and clinodactyly. Facial features commonly associated with this syndrome are a small triangular face, decreased facial height, down-turned corners of the mouth(shark's mouth), a small mandible, and occasionally asymmetry. The major intra-oral features of the syndrome that have been reported are a high-arched palate, delayed tooth eruption, microdontia, hypodontia, and crowding. These cases were diagnosed at birth as Russell-Silver syndrome by clinical features such as prenatal growth retardation, short stature, low body weight, et al., and have been treated with growth hormone. The purpose of this paper is to report the dental findings of two patients and review the pertinent literature through the two cases.