• Toxicological Research
• /
• v.29 no.1
• /
• pp.27-34
• /
• 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.

• Advances in pediatric surgery
• /
• v.3 no.1
• /
• pp.15-23
• /
• 1997

During a 6-year period, from January 1990 to December 1995, 101 neonates with congenital anomalies were admitted to the division of Pediatric Surgery of Youngdong Severance Hospital. All of them had prenatal screening more than once with ultrasound. Fifty eight of them had prenatally detectable anomalies by ultrasonography. However abnormalities were prenatally detected in 24 neonates(41%). The detection rate was 70% in patientws who had the prenatal screening at our hospital, whereas, the rate was 24% when it was performed at other medical facilities. Duodenal and jejuno-ileal atresia showed the highest detection rate(86%) followed by abdominal mass. Esophageal atresia was suggested by maternal polyhydramnios in 3 patients (25%). Only one patient with diaphragmatic hernia(1.75%) was prenatally detected and none with gastroschisis. The mean interval from birth to operation was 32 hours in the prenatally detected patients and 50 hours in the non detected. The complication rate and the mortality after emergency operation were 20% and 7% in the detected group, and 58% and 23% in the nondetected, respectively. The average period of the hospitalization was 20 days in the detected group and 39 days in the nondetected. We conclude that the prenatal detection of anomalies is necessary to ensure adequate care for the mothers and the babies with congenital anomalies. This includes early transfer, timing of optimal delivery and operation.

• Korean Journal of Veterinary Research
• /
• v.30 no.2
• /
• pp.123-127
• /
• 1990

By nuclear transplantation technology twenty eight mice have been produced after transfer of heterozygous biparental eggs. Also heterozygous gynogenetic eggs with two female pronuclei and heterozygous androgenetic eggs with two male pronuclei have been obtained by injecting a male or female pronucleus with Sendai virus into the perivitelline space of enucleated haploid zygotes at pronuclear stage. The success rate of enucleation, karyoplast injection and fusion of both the pronuclei was 80.3, 83.4 and 81.8%, respectively. The overall pronuclei fusion rates by this technique were 56, 50 and 56% in biparental, gynogenetic and androgenetic eggs, respectively. The evidence was ascertained that the gynogenetic and androgenetic eggs were also able to develop in vitro up to blastocyst stage, even though their developmental potential was greatly diminished beyond 2-cell stage. The gynogenetic eggs were able to develop in vivo up to day 10 of pregnancy, while the androgenetic eggs failed to develop in vivo during the same period.

• Clinical and Experimental Reproductive Medicine
• /
• v.38 no.3
• /
• pp.126-134
• /
• 2011

Preimplantation genetic diagnosis (PGD) is gradually widely used in prevention of gene diseases and chromosomal abnormalities. Much improvement has been achieved in biopsy technique and molecular diagnosis. Blastocyst biopsy can increase diagnostic accuracy and reduce allele dropout. It is cost-effective and currently plays an important role. Whole genome amplification permits subsequent individual detection of multiple gene loci and screening all 23 pairs of chromosomes. For PGD of chromosomal translocation, fluorescence $in-situ$ hybridization (FISH) is traditionally used, but with technical difficulty. Array comparative genomic hybridization (CGH) can detect translocation and 23 pairs of chromosomes that may replace FISH. Single nucleotide polymorphisms array with haplotyping can further distinguish between normal chromosomes and balanced translocation. PGD may shorten time to conceive and reduce miscarriage for patients with chromosomal translocation. PGD has a potential value for mitochondrial diseases. Preimplantation genetic haplotyping has been applied for unknown mutation sites of single gene disease. Preimplantation genetic screening (PGS) using limited FISH probes in the cleavage-stage embryo did not increase live birth rates for patients with advanced maternal age, unexplained recurrent abortions, and repeated implantation failure. Polar body and blastocyst biopsy may circumvent the problem of mosaicism. PGS using blastocyst biopsy and array CGH is encouraging and merit further studies. Cryopreservation of biopsied blastocysts instead of fresh transfer permits sufficient time for transportation and genetic analysis. Cryopreservation of embryos may avoid ovarian hyperstimulation syndrome and possible suboptimal endometrium.

• Journal of Korean Neurosurgical Society
• /
• v.66 no.3
• /
• pp.228-238
• /
• 2023

Intraventricular hemorrhage (IVH) is a serious concern for preterm infants and can predispose such infants to brain injury and poor neurodevelopmental outcomes. IVH is particularly common in preterm infants. Although advances in obstetric management and neonatal care have led to a lower mortality rate for preterm infants with IVH, the IVH-related morbidity rate in this population remains high. Therefore, the present review investigated the pathophysiology of IVH and the evidence related to interventions for prevention. The analysis of the pathophysiology of IVH was conducted with a focus on the factors associated with cerebral hemodynamics, vulnerabilities in the structure of cerebral vessels, and host or genetic predisposing factors. The findings presented in the literature indicate that fluctuations in cerebral blood flow, the presence of hemodynamic significant patent ductus arteriosus, arterial carbon dioxide tension, and impaired cerebral venous drainage; a vulnerable or fragile capillary network; and a genetic variant associated with a mechanism underlying IVH development may lead to preterm infants developing IVH. Therefore, strategies focused on antenatal management, such as routine corticosteroid administration and magnesium sulfate use; perinatal management, such as maternal transfer to a specialized center; and postnatal management, including pharmacological agent administration and circulatory management involving prevention of extreme blood pressure, hemodynamic significant patent ductus arteriosus management, and optimization of cardiac function, can lower the likelihood of IVH development in preterm infants. Incorporating neuroprotective care bundles into routine care for such infants may also reduce the likelihood of IVH development. The findings regarding the pathogenesis of IVH further indicate that cerebrovascular status and systemic hemodynamic changes must be analyzed and monitored in preterm infants and that individualized management strategies must be developed with consideration of the risk factors for and physiological status of each preterm infant.

• Journal of Embryo Transfer
• /
• v.31 no.4
• /
• pp.335-347
• /
• 2016

Multiple interferon tau (IFNT) genes exist in bovine. An antiluteolytic substance secreted by the bovine conceptus and primarily responsible for maternal recognition of pregnancy is bovine trophoblast protein 1 (bIFNT1), a new type I interferon tau (IFNT) genes. The objectives of this research were to investigate whether multiple, distinct gene encode bIFNT1 and other type I bIFNT gene in the bovine genome and to examine expression of bIFNT1 and other bIFNTc1 mRNAs during conceptus development. These transcrips could be regulated through caudal-related homeobox-2 (CDX2) and ETS2 and/or AP1 (JUN) expression, a transcription factor implicated in the control of cell differentiation in the trophectoderm. The presence of mRNAs encoded by bIFNT1 and type I bIFNTc1 genes were examined quantitatively via reverse transcription-polymerase chain reaction (RT-PCR) analysis of total cellular RNA (tcRNA) extracted from on day 17, 20 and 22 bovine conceptuses. The expression level of bIFNT1 was higher on day 17 transcripts were gradually weakly detectable on day 20 and 22. However, the other bIFNTc1 gene examined transcripts was highly expressed on day 20 and transcripts were weakly detectable on day 17 and 22 bovine conceptuses. Furthermore, human choriocarcinoma JEG3 was co-transfected with an -1kb-bIFNT1/c1-Luc constructs and several transcription factor expression plasmids. Compared to each -1kb-bIFNT1/c1-Luc increased when this constructs were co-transfected with, ETS2, AP1(JUN), CREBBP and/or CDX2. Also, bIFNTc1 gene was had very effect on activity by alone ETS2, and AP1 (JUN) expression factors in choriocarcinoma JEG3 cell. However, bIFNT1 gene expression of the upstream region was not identified. We demonstrated that the activities of bIFN genes are regulated by differential, tissue-specific and developmental competence during pregnancy.

• Asian-Australasian Journal of Animal Sciences
• /
• v.16 no.3
• /
• pp.348-352
• /
• 2003

An investigation was made into the protein profile of colostrum/milk of ten Murrah buffaloes and of their ten buffalo calves during their first week of neonatal life to study the materno-neonatal transfer of immunoglobulins (Ig). Calves were pail fed 3.5 liter of colostrum and/or milk per calf/day exclusively from their dam. First blood sample from newborn calves was collected before colostrum feeding on the day of birth (day zero) and the sampling continued daily for seven days after colostrum/milk feeding. Colostrum/milk Ig and IgG values were $4.82{\pm}2.60$, $2.19{\pm}1.90$, $1.12{\pm}0.82$, $0.69{\pm}0.44$, $0.59{\pm}0.31$, $0.47{\pm}0.20$, $0.40{\pm}0.22$, $0.40{\pm}0.25$ and $3.58{\pm}1.90$, $1.08{\pm}0.92$, $0.52{\pm}0.40$, $0.31{\pm}0.20$, $0.27{\pm}0.14$, $0.22{\pm}0.08$, $0.18{\pm}0.09$, $0.14{\pm}0.08$ respectively during 0-7 days post partum. The concentration of total colostrum/milk proteins, Ig, IgG and albumin were highest within 12 h post-partum. Thereafter, the concentrations followed a declining trend which may be attributed to the reduced transfer of proteins from the maternal blood, declining synthesis by the mammary glands and/or depletion of stored proteins. The concentrations of plasma Ig and IgG before colostrum feeding on day zero were $0.42{\pm}0.09$ and $0.08{\pm}0.03$ respectively. The levels of plasma Ig were $1.90{\pm}0.37$, $1.80{\pm}0.31$, $1.80{\pm}0.26$, $1.81{\pm}0.28$, $1.78{\pm}0.31$, $1.79{\pm}0.21$, $1.80{\pm}0.32$ and of IgG were $1.57{\pm}0.41$, $1.30{\pm}0.29$, $1.31{\pm}0.21$, $1.27{\pm}0.18$, $1.23{\pm}0.21$, $1.23{\pm}0.16$, $1.26{\pm}0.21$ on days 1-7 after birth after colostrum/milk feeding. The concentrations of total plasma proteins, Ig, IgG were lowest before colostrum feeding and increased significantly (p<0.05) after colostrum feeding in buffalo neonates. The results suggest that the highest amounts of colostral Ig and IgG were available on the day of parturition and thus the calves should receive colostrum as early after birth as possible. Colostrum Ig and IgG concentrations were not correlated to plasma Ig and IgG concentrations in the post-suckle buffalo calves and therefore, colostrum Ig and IgG concentrations were probably not the principle determinants of calf post-suckle plasma Ig and IgG concentrations.

• Clinical and Experimental Reproductive Medicine
• /
• v.26 no.1
• /
• pp.75-81
• /
• 1999

The beneficial effect of glucose and phosphate ions in culture medium on the development of human embryos in vitro has not been fully elucidated. The purpose of this study was to evaluate the influence of fertilization and culture of embryos in glucose/phosphate-free m-TALP medium on pregnancy rates in IVF-ET program. The patients in 244 IVF-ET cycles received GnRH agonist + HMG regimens. A does of 10,000 IU HCG was administered when two or more dominent follicles reached 18mm in diameter. Thirty-six hours after HCG, oocytes were recovered transvaginally using ultrasound guidance. Aspirated oocytes were matured for 4 to 6 h in TCM-199 supplemented with 10% follicular fluid (FF). Insemination was carried out with 50,000 motile spermatozoa in TCM-199 + 10% FF or m-TALP + 5% FF + 5% fetal cord serum (FCS) according to experimental design. After 6 h, oocytes were washed 3 to 4 times and cultured in each fresh medium. After 20 h, oocytes were freed from cumulus/corona cells and examined for the presence of pronuclei. Fertilized oocytes were transferred into each co-culture drops and cultured for further incubation. On day 3, embryo transfer was performed with grade 1 and 2 embryos. Monolayers for co-culture of embryos were prepared by plating $1{\times}10^5$ cumulus cells/ml in 10ul drop of TCM-199 + 10% FF or m-TALP + 5% FF + 5% FCS media 24 h prior to the onset of co-culture. Development to 4 to 16 cell stage was observed at 70x magnification following two days of incubation. Pregnancy was confirmed by detecting increasing serum ${\beta}$-hCG concentrations for 11 days following embryo transfer. Data were analyzed by ${\chi}^2$-test. Oocytes from 244 IVF-ET cycles were randomized. The number of cycles and mean age of patients were 97 and 147, 31.3 yrs and 31.2 yrs for TCM-199 (control) and m-TALP groups, respectively. The mean number of retrieved oocytes/cycle, fertilization rates, number of embryos transferred/ET and pregnancy rates were 11.1 and 10.3, 65.1% and 67.3%, 4.1 and 4.7, 28.9% and 43.8% for TCM-199 and m-TALP groups, respectively. Differences in the pregnancy rates were found between control and m-TALP groups (p<0.05). The pregnancy rate of patients divided according to maternal age groups of ${\leq}30$, 31-35, $36{\leq}$ were 44.4% and 49.0%, 26.1% and 41.3%, 29.2% and 41.2% for control and m-TALP groups, respectively. These data indicate that culture of human embryos in glucose/phosphate-free m-TALP medium improves pregnancy rates.

• Journal of Embryo Transfer
• /
• v.33 no.4
• /
• pp.195-203
• /
• 2018

Interferon-tau (IFNT) is known as a major conceptus protein that signals the process of maternal recognition of pregnancy in ruminants. Also, multiple interferon genes exist in cattle, However, molecular mechanisms of these bovine IFNT (bIFNT) genes whose expressions are limited have not been characterized. We and others have observed that expression levels of bovine subtype IFNT genes in the tissues of ruminants; thus, bIFNT1 and other new type I (bIFNTc1/c2/c3) gene co-exist during the early stages of conceptus development and non-trophoblast cells. Its genes transcription could be regulated through CDX2 and ETS2 and JUN and/or cAMP-response element binding protein (CREB)-binding protein (CREBBP) expression, a transcription factor implicated in the control of cell differentiation in the trophectoderm. Bovine ear-derived fibroblast cells, were co-transfected with luciferase reporter constructs carrying upstream (positions -1000 to +51) regions of bIFNT1 and other new type I gene and various transcription factor expression plasmids. Compared to each - 1kb-bIFNT1/c1/c2/c3-Luc increased when this constructs were co-transfected with CDX2, ETS2, JUN and/or CREBBP. Also, Its genes was had very effect on activity by CDX2, either alone or with the other transcription factors, markedly increased luciferase activity. However, the degree of transcriptional activation of the bIFNTc1 gene was not similar to that bIFNT1/c2/c3 gene by expression plasmid. Furthermore, Sequence analyses also revealed that the expression levels of bIFNT1/c2/c3 gene mRNAs expression were highest on day 17, 20 and 22 trophoblast and, Madin-Darby bovine kidney (MDBK), Bovine ear-derived fibroblast (EF), and endometrium (Endo) non-trophoblast cells. But, bIFNTc1 mRNA had not same expression level, bIFNTc1 lowest levels than those of IFNT1/c2/c3 gene in both trophoblast and non-trophoblast cells. These results demonstrate that bovine subtype bIFNT genes display differential, in the trophoblast and non-trophoblast cells.

• Clinical and Experimental Reproductive Medicine
• /
• v.17 no.1
• /
• pp.45-56
• /
• 1990

Maternal serum ${\beta}$-specific human chorionic gonadotropin(${\beta}$-hCG) and pregnancy-specific ${\beta}_1$-glycoprotein($SP_1$) levels were determined more than one per week during 11-41 days post embryo transfer(ET) in 21 consecutive pregnancies after in vitro fertilization(IVF), which included 8 normal singleton pregnancies, 3 twin pregnancies, 4 clinical abortions, 1 ectopic pregnancy, and 5 preclinical abortions. The sensitivity of serum ${\beta}$-hCG and $SP_1$ radioimmunoassays was 3mIU/ml and 0.7ng/ml relatively. At the 7th to 8th week of gestation, ultrasonographic confirmation of fetal pole and fetal heartbeat was performed. Both serm ${\beta}$-hCG and $SP_1$ levels showed logarithmic increase, but log[$SP_1$] had more steep rising curve and had wider variation than log[${\beta}$-hCG] in normal singleton pregnancies. In 3 twin pregnancies and one ectopic pregnancy, both serum ${\beta}$-hCG and $SP_1$ levels located within the 95% confidence interval of the mean levels of 8 normal singleton pregnancies(normal range). In 2 clinical abortions which had a fetal pole without heartbeat, serum ${\beta}$-hCG level showed lower limit of the normal range or just below, but all $SP_1$ levels showed within the normal range. In other 2 clinical abortions which were diagnosed as blighted ovum, both serum ${\beta}$-hCG levels from 11 days post-ET and serum $SP_1$ levels from later days compared with ${\beta}$-hCG were below the normal range. In 5 preclinical abortions, serum $SP_1$ levels were within the normal range but serum ${\beta}$-hCG levels were far below the normal range. In conclusion, both serum ${\beta}$-hCG and $SP_1$ levels increased exponentially with similar pattern in normally conceived pregancy after IVF-ET. Both serum ${\beta}$-hCG and $SP_1$ levels could predict outcome of early pregnancy to a certain degree, but log[${\beta}$-hCG] levels had more significant correlation with outcome of pregnancy compared with log[$SP_1$] levels. In addition, ultrasonographic examination of fetal poles and fetal heartbeats gives very important clinical information and prognosis.