Kinetics of fetal cellular and cell-free DNA in the maternal circulation during and after pregnancy: implications for noninvasive prenatal diagnosis

Kinetics of fetal cellular and cell-free DNA in the maternal circulation during and after pregnancy: implications for noninvasive prenatal diagnosis
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DOI:
10.1046/j.1537-2995.2001.41121524.x
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发表时间:
2001-12-01
期刊:
影响因子:
2.9
通讯作者:
Lee, TH
Lee, TH
中科院分区:
医学3区
文献类型:
--
作者:
Ariga, H;Ohto, H;Lee, TH

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背景:胎儿遗传物质在母体循环中是可检测的,并已被用于无创性产前诊断。然而,很少有数据是关于它的数量和自然历史在gestation.Study设计和方法:本研究前瞻性的特点是在25个健康妇女的循环中的细胞和无细胞的胎儿DNA的动力学在简单的怀孕期间和之后。采用实时荧光定量PCR技术对人Y染色体进行定量分析,用P-32标记探针进行寡聚体杂交验证扩增产物的同一性。在所有男性怀孕中,但没有女性怀孕,低水平的胎儿Y染色体DNA检测细胞和细胞,游离隔室在7 - 16周开始,但在24周后稳定增加,并在分娩时达到高峰。胎儿DNA在出生后迅速下降。结论:胎儿遗传物质可以在整个妊娠期间检测到,其数量是孕龄和是否检查血浆或细胞室的函数。胎儿DNA的绝对量及其与总DNA(母体+胎儿)的比率在血浆中比在细胞区室中更大。胎儿DNA在分娩后从两个隔室中迅速清除,这表明周转是动态的。因为它们提供了关于胎儿DNA水平的前瞻性和定量数据,这些观察和动力学PCR方法可能对非侵入性产前诊断有影响。需要进一步的研究来确定胎儿-母体DNA交换和细胞微嵌合体的免疫学意义。
BACKGROUND: Fetal genetic material is detectable in the maternal circulation and has been used for noninvasive prenatal diagnosis. However, few data are available concerning its quantity and natural history during gestation.STUDY DESIGN AND METHODS: This study prospectively characterized the kinetics of cellular and cell-free fetal DNA in the circulation of 25 healthy women during and after uncomplicated pregnancy. Real-time kinetic PCR was used to quantitate human Y-chromosome sequences, and liquid oligomer hybridization with P-32-labeled probes was used to verify the identity of amplified products.RESULTS: In all male pregnancies, but no female pregnancies, low-level fetal Y-chromosome DNA was detected in both cellular and cell-free compartments beginning at 7 to 16 weeks but increasing steadily after 24 weeks and reaching a peak at parturition. The fetal DNA decreased rapidly after birth.CONCLUSION: Fetal genetic material can be detected throughout pregnancy, and its quantity is a function of gestational age and of whether the plasma or cellular compartment is examined. Both the absolute quantity of fetal DNA and its ratio to total DNA (maternal + fetal) are greater in the plasma than in the cellular compartment. Fetal DNA is cleared rapidly from both compartments after parturition, which suggests that turnover is dynamic. Because they provide prospective and quantitative data concerning fetal DNA levels, these observations and kinetic PCR methods may have implications for noninvasive prenatal diagnosis. Further studies will be needed to determine the immunologic implications of fetal-maternal DNA exchange and cellular microchimerism.