Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum
Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum
复制标题
DOI：
10.1073/pnas.93.2.705
复制
发表时间：
1996-01-23
影响因子：
11.1
通讯作者：
DeMaria, MA
中科院分区：
文献类型：
--
作者：
Bianchi, DW;Zickwolf, GK;DeMaria, MA
稀有的有核胎儿细胞在母体血液中循环。目前正在通过对这些细胞的分离和遗传分析进行无创产前诊断。我们试图确定是否存在遗传证据表明先前怀孕的胎儿细胞持续循环。静脉血样本取自 32 名孕妇和 8 名在 6 个月至 27 年前生过男性的非孕妇。使用 CD 抗原 3、4、5、19、23、34 和 38 的抗体，通过流式细胞术对单核细胞进行分选。分选细胞内的 DNA，通过 PCR 扩增 Y 染色体序列，被认为是男性胎儿的预测或持久男性胎儿细胞的证据。在这 32 次怀孕中，19 名怀有男性胎儿的女性中有 13 名检测到了男性 DNA。 13 名女性胎儿中，有 4 名也检测到了男性 DNA。这 4 名女性均曾怀孕过； 4 人中有 2 人以前有过男性，另外 2 人终止妊娠。在 8 名非孕妇中，有 6 名在 CD34(+)CD38(+) 细胞中检测到了男性 DNA，甚至在采血前 27 年前生下最后一个儿子的女性中也是如此。我们的数据表明，来自先前妊娠的胎儿CD34(+)或CD34(+)CD38(+)细胞在母体内持续循环。胎儿祖细胞的长期存在可能代表了小鼠中描述的微嵌合现象的人类类似物，并且可能对胎儿耐受性的发展具有重要意义。因此，怀孕可能会在人类女性中建立一种长期的、低级的嵌合状态。
Rare nucleated fetal cells circulate within maternal blood. Noninvasive prenatal diagnosis by isolation and genetic analysis of these cells is currently being undertaken. We sought to determine if genetic evidence existed for persistent circulation of fetal cells from prior pregnancies. Venous blood samples were obtained from 32 pregnant women and 8 nonpregnant women who had given birth to males 6 months to 27 years earlier. Mononuclear cells were sorted by flow cytometry using antibodies to CD antigens 3, 4, 5, 19, 23, 34, and 38. DNA within sorted cells, amplified by PCR for Y chromosome sequences, was considered predictive of a male fetus or evidence of persistent male fetal cells. In the 32 pregnancies, male DNA was detected in 13 of 19 women carrying a male fetus. In 4 of 13 pregnancies with female fetuses, male DNA was also detected. All of the 4 women had prior pregnancies; 2 of the 4 had prior males and the other 2 had terminations of pregnancy. In 6 of the 8 nonpregnant women, male DNA was detected in CD34(+)CD38(+) cells, even in a woman who had her last son 27 years prior to blood sampling. Our data demonstrate the continued maternal circulation of fetal CD34(+) or CD34(+)CD38(+) cells from a prior pregnancy. The prolonged persistence of fetal progenitor cells may represent a human analogue of the microchimerism described in the mouse and may have significance in development of tolerance of the fetus. Pregnancy may thus establish a long-term, low-grade chimeric state in the human female.