• 제목/요약/키워드: Placenta transfer

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Placenta Transfer and Toxicokinetics of Valproic Acid in Pregnant Cynomolgus Monkeys

  • Jeong, Eun-Ju;Yu, Wook-Joon;Kim, Choong-Yong;Chung, Moon-Koo
    • Toxicological Research
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    • 제26권4호
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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.

랫드에서 fluoroquinolone 항균제 DW-116의 단회 경구투여에 의한 태반통과와 약물동태연구 (Placental Transfer and Pharmacokinetics of a Single Oral Dose of the Fluoroquinolone Antibacterial DW-116 in Rats)

  • 김종춘;신호철;허정두;이종화;정문구;윤효인
    • Biomolecules & Therapeutics
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    • 제10권1호
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    • pp.43-49
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    • 2002
  • The present study was conducted to investigate the placental transfer and pharmacokinetics of the flu-oroquinolone antibacterial DW-116 in pregnant rats. The placental transfer and pharmacokinetics of DW-116 were examined after a single oral dose of 500 mg $^{14}C$ DW-116/kg on gestational day 18. Maternal and fetal tissues were collected at 0.17 0.5,1,2,4,8, and 24 h after dosing. Maximum radioactivity was detected in maternal plasma, placenta, and whole fetus at 1 h, and in amniotic plasma at 4 h after dosing. Thereafter, radioactivity gradually disappeared from these tissues and was 16~28% of maximum levels at 24 h after dosing. Radioactivity in whole fetus were higher than those in the maternal plasma and placenta. The $T_{1/2,abs}$, $T_{1/2,{\beta}},$ AUC, $T_{max},$ and $C_{max}$ in the maternal plasma were approximately 6 min, 13.3 h, 1620 $ug^*hr/ml,$ 0.5 h, and 136 ug/ml, respectively. Those in the placenta were approximately 20 min, 12.3 h, 2150 $ug^*h/$m\ell$,$ 1.0 h, and 172 ug/ml, respectively. Those in the whole fetus were 13 min, 12.8 h,2549 $ug^*h/$m\ell$,$ 1 h, and 191 ug/ml, respectively. In the amniotic fluid of maternal uterus, the 4T_1/2,abs}$, $T1/2,{\beta},$ AUC, $T_{max},$ and $C_{max}$ were approximately 1.3 h,9.3 h,2508 $ug^*h/$m\ell$,$ 4.4 h, and 135 ug/ml, respectively. While DW-116 disappeared biphasically from maternal plasma, whole fetus and placenta, it was eliminated monophasically from amniotic fluid. In conclusion, this study demonstrated that the absorption and distribution of DW-116 in maternal plasma and placenta were extensively rapid, and that the test chemical well passed the blood-placenta barrier and was transferred to the fetus.

토끼 태반을 통한 $Li^+$이동에 관한 연구 (Transfer of Lithium ion in the Placenta of the Rabbit)

  • 성호경;김전
    • The Korean Journal of Physiology
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    • 제18권1호
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    • pp.1-8
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    • 1984
  • In order to determine the extent of the placental transfer of Lithium ion, pregnant rabbits at $27{\sim}29$ days of gestation, which has hemochorial placenta similar to the human placenta, received 2 mM/Kg of $Li^+$ in the form of LiCl intravenously. Maternal arterial blood, placental sinus blood, fetal blood, amniotic fluid and maternal urine were drawn two hours after the single dose of LiCl. Concentrations of $Li^+$, $Na^+$, $K^+$ and osmolarity were measured in plasma of collected bloods, amniotic fluid and urine. Followings are the results obtained. 1) Evident level of $Li^+$ was detected in fetal blood, although fetal plasma concentration of $Li^+$ found to be almost one third of maternal plasma. 2) Plasma concentration of $Li^+$ in placental sinus blood was higher than that in fetal plasma but lower than that in maternal plasma. It means that downward concentration gradient of $Li^+$ from mother to fetus was still remarkable two hours after the injection. 3) Significant level of $Li^+$ was also detected in amniotic fluid. It seemed likely that $Li^+$, at least in part, excreted by the fetal urinary tract. 4) There were no differences in $Na^+$ and osmolar concentration between fetal and maternal blood. 5) From above results, it was concluded that $Li^+$ may transfer across the placenta but limited passage capacity through placental barrier for $Li^+$ is significant, beacause net transfer assumed to be going on even at two hours, at which time maternal equlibrium has been reached.

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Mammary Excretion and Placental Transfer of Bisphenol A in Rats

  • Yoo, Sun-Dong
    • 한국발생생물학회:학술대회논문집
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    • 한국발생생물학회 2001년도 전기 제11차 학술대회 논문집
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    • pp.27-31
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    • 2001
  • This study examined the extent of mammary excretion and placental transfer of bisphenol A in rats. Bisphenol A was given by simultaneous i.v. bolus injection plus infusion to steady-state at low, medium and high doses. The steady-state serum levels of bisphenol A were linearly increased with increasing the dosing rate. The systemic clearance (mean range, 119.2-154.1 ml/min/kg) remained unaltered over the dosing rate studied. The levels of bisphenol A in milk exceeded those in serum, with the steady-state milk to serum concentration ratio being 2.4-2.7. The steady-state milk levels of bisphenol A were also increased linearly with increasing the infusion rate. In a separate study, the kinetic disposition of bisphenol A in the rat maternal-fetal unit was studied in pregnant rats. After i.v. injection, bisphenol A concentration in the maternal serum declined biexponentially. Bisphenol A was rapidly distributed into placenta, fetus and amniotic fluid, with maximum concentrations in these tissues achieved within 1 hr of injection. The decline of bisphenol A in placenta, fetus and amniotic fluid paralleled that of maternal serum. A simultaneous computer simulation showed that the observed concentrations were well represented by a 5-compartmental model consisting of the maternal central, placenta, fetus, amniotic fluid, and maternal tissue compartments.

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Characterization of Placental Proteins in Bovine Somatic Cell Clone Fetuses

  • Woo, Jei-Hyun;Ko, Yeoung-Gyu;Kim, Bong-Ki;Kim, Jong-Mu;Lee, Youn-Su;Kim, Nam-Yun;Im, Gi-Sun;Yang, Boung-Chul;Seong, Hwan-Hoo;Jung, Jin-Kwan;Kwun, Moo-Sik;Chung, Hak-Jae
    • Reproductive and Developmental Biology
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    • 제29권2호
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    • pp.83-91
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    • 2005
  • Somatic cell nuclear transfer in cattle has limited efficiency in terms of production of live offspring due to high incidence of fetal failure after embryo transfer to recipients. Such low efficiency of cloning could possibly arise from abnormal and poorly developed placenta. In the present study the placental proteome in late pregnancy established from in vitro fertilization (IVF) and nuclear transfer (NT) was analysed. Proteome alternation was tested using two-dimensional polyacrylamide gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI- TOF). Comparing placenta from NT embryos to those from IVF counterparts, significant changes in expression level were found in 18 proteins. Of these proteins 12 were not expressed in NT placenta but expressed in IVF counterpart, whereas the expression of the other 6 proteins was limited only in NT placenta. Among these proteins, cytokeratin 8 and vimentin are considered to be involved in regulation of post-implantation development. In particular, cytokeratin 8 and vimentin may be used as makers for placental development during pregnancy because their expression levels changed considerably in NT placental tissue compared with its IVF counterpart. Data from 2-DE suggest that protein expression was disorientated in late pregnancy from NT, but this distortion was eliminated with progression of pregnancy. These findings demonstrate abnormal placental development during late pregnancy from NT and suggest that alterations of specific placental protein expression may be involved in abnormal function of placenta.

수용성카이토산에 의한 마우스태반을 통한 태아로의 방사성스트론튬 급성 전이 억제 (Blocking the Acute Radiostrontium Transfer from Placenta In Fetus by Soluble Chitosan in Mice)

  • 김영호;범희승;김지열
    • Journal of Radiation Protection and Research
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    • 제22권4호
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    • pp.237-250
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    • 1997
  • 카이토산은 천연무독성 착화제의 일종으로 유전적 독성이 거의 없으며, 방사성스트론튬의 마우스 체내 축적을 감소시킨다고 알려져 왔다. 본 연구에서는 임신 17일째 마우스에서 방사성스트론튬 오염전 후에 수용성카이토산을 공급함으로써 오염 후 태반을 통한 태아로의 방사성스트론튬 급성 전이를 얼마나 효과적으로 억제할 수 있는 가를 알아보고자 하였다. 수용성카이토산 분말을 50일간 일반식이와 혼합하여 10% (Group 1), 1%(Group 2)를 공급하고 임신 17일째에 방사성스트론튬을 오염시킨 군의 경우 일반식이를 공급한 대조군과 방사성스트론튬 오염 후 카이토산 10%, 1%분말을 공급한 군(Group 3, Group 4)에 비해 태반을 통한 태아로의 방사성스트론튬 전이를 효과적으로 억제함을 관찰하였다(p<0.01, 표 1).본 실험을 통해서 임신 17일째에 방사성스트론튬에 오염된 임신마우스의 경우 천연무독성 착화제인 카이토산을 장기간 전처치하였을 경우 태반을 통한 태아로의 방사성스트론튬 전이를 억제할 수 있음을 알 수 있었다.

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A Transfer of Silver Nanoparticles from Pregnant Rat to Offspring

  • Lee, Yeon-Jin;Choi, Jong-Hye;Kim, Pil-Je;Choi, Kyung-Hee;Kim, Su-Hyon;Shon, Woo-Chan;Park, Kwang-Sik
    • Toxicological Research
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    • 제28권3호
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    • pp.139-141
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    • 2012
  • Silver nanoparticles (size: $7.9{\pm}0.95$ nm, dosage: 250 mg/kg) were orally administered to pregnant rats. At 4 days after parturition, four pups were randomly selected (one pup from one dam) and silver level in liver, kidney, lung and brain was determined by ICP-MS and electron microscope. As results, silver nanoparticles highly accumulated in the tissues of the pups. Silver level in the treated group was $132.4{\pm}43.9$ ng/g in the kidney (12.3 fold compared to control group), $37.3{\pm}11.3$ ng/g in the liver (7.9 fold), $42.0{\pm}8.6$ ng/g in the lung (5.9 fold), and $31.1{\pm}4.3$ ng/g in the brain (5.4 fold). This result suggested that the possible transfer of silver nanoparticles from pregnant dams to the fetus through mainly placenta.

Differentially Expression Genes of Normal and Cloned Bovine Placenta

  • Kim, M.S.;Lee, Y.Y.;Park, J.J.;H.Y. Kang;Y.M. Chang;Yoon, J.T.;K.S. Min
    • 한국발생생물학회:학술대회논문집
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    • 한국발생생물학회 2003년도 제3회 국제심포지움 및 학술대회
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    • pp.82-82
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    • 2003
  • Offspring have been produced from somatic cells in a number of species. This biotechnology introduced a new phenomenon in reprogramming and differentiation of somatic cell, namely totipotency. However, birth of oversized calves and perinatal abnormalities such as increased gestation length, lack of spontaneous parturition, higher incidence of dystocia, and reduced perinatal viability of offspring are frequently observed in pregnancies of cloned bovine fetuses. Disturbance of feto-placenta has been proposed as likely causes for abnomal growth. However. Little is known the mechanism responsible for the perinatal problems. Therefore, we focused on gestation length in somatic cell nuclear recipient cows. To solve this issues, placental tissues of control and cloned bovine were obtained by a cesarean section (C-section) before 5 days of paturition. Total RNA from control and cloned bovine placenta was extractd by TRIzol reagent. GeneFishing DEG kits (Seegene) were used to identify differentially expression genes. Total RNA (3 ug) were synthesized by M-MLV reverse transcriptase (200 u/ul) with 10 uM dT-annealing control primer (ACP1) at 42C for 90 min. Then, first-strand cDNA (50 ng) was amplified using the 5 uM arbitary ACP (1-20) and 10 uM dT-ACP2 primers. Some specific expression genes were amplified, Now, we are cloning and sequencing. These finding strongly can be support to solve the problems for parturition delay in nuclear transfer cows, suggest that placenta specific proteins are key indicators for the aberration of gestation and placental function in cows.

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