Fetal cell-free DNA circulates in the plasma of pregnant mice: relevance for animal models of fetomaternal trafficking.

Fetal cell-free DNA circulates in the plasma of pregnant mice: relevance for animal models of fetomaternal trafficking.
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胎儿游离 DNA 在怀孕小鼠血浆中循环:与母胎贩运动物模型的相关性。

DOI:
10.1093/humrep/deh445
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发表时间:
2004
期刊:
Human reproduction (Oxford, England)
影响因子:
--
通讯作者:
Johnson,KirbyL
Johnson,KirbyL
中科院分区:
--
文献类型:
--
作者:
Khosrotehrani,Kiarash;Wataganara,Tuangsit;Bianchi,DianaW;Johnson,KirbyL

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背景:胎儿游离DNA(fDNA)可在整个人类妊娠期的母体血浆中检测到,并在分娩后迅速清除。fDNA测量在许多妊娠并发症中具有临床应用。我们的目的是确定在小鼠模型系统中是否可以在妊娠期间在母体血浆中检测到fDNA。然后,我们比较了母亲和胎儿在怀孕期间的fDNA水平,其中母亲和胎儿是同源的或同种异体的。方法:将C57 BL/6 J(H-2b)或DBA/2 J(H-2d)野生型雌性小鼠与增强型绿色荧光蛋白(gfp)转基因的C57 BL/6 J小鼠交配,并在妊娠时处死。在分娩后处死先前在与转基因雄性交配后产下3至6窝的C57 BL/6 J雌性小鼠。我们使用实时定量PCR扩增来检测和测量孕妇血浆中的fp序列。研究结果:妊娠期间在母体血浆中始终检测到fDNA,并且在分娩后始终不存在[中位数分别为211基因组当量(GE)/ml vs 0 GE/ml,P=0.0001]。与同源交配相比,同种异体交配中的fDNA水平更高(分别为中位数167 GE/ml/GFP +胎儿vs 81 GE/ml/GFP +胎儿)。结论:小鼠妊娠期间可以在母体血浆中可靠地检测到fDNA序列。我们的数据进一步支持使用非人类物种调查的机制,参与了母胎贩运。
BACKGROUND: Cell-free fetal DNA (fDNA) can be detected in maternal plasma throughout human pregnancy and is rapidly cleared after delivery. fDNA measurement has clinical application in many complications of pregnancy. Our aim was to determine if fDNA could be detected in maternal plasma during pregnancy in a mouse model system. We then compared the levels of fDNA during pregnancies in which the mother and fetus were either congenic or allogenic. METHODS: C57BL/6J (H-2b) or DBA/2J (H-2d) wild-type female mice were mated to C57BL/6J mice transgenic for the enhanced green fluorescent protein (gfp) and sacrificed while pregnant. C57BL/6J female mice that had previously given birth to three to six litters after mating with transgenic males were sacrificed after delivery. We used real-time quantitative PCR amplification to detect and measuregfpsequences in maternal plasma. RESULTS: fDNA was consistently detected in maternal plasma during pregnancy and was always absent after delivery [median 211 genome equivalents (GE)/ml vs 0 GE/ml, respectively,P=0.0001]. The level of fDNA was higher in allogenic matings compared to congenic matings (median 167 GE/ml/GFP + fetus vs 81 GE/ml/GFP + fetus, respectively). CONCLUSIONS: fDNA sequences can be reliably detected in maternal plasma during murine pregnancy. Our data lends further support to the use of nonhuman species to investigate the mechanisms involved in fetomaternal trafficking.
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