Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
PLoS One. 2011;6(8):e24101. doi: 10.1371/journal.pone.0024101. Epub 2011 Aug 30.
A WOMAN OF REPRODUCTIVE AGE OFTEN HARBORS A SMALL NUMBER OF FOREIGN CELLS, REFERRED TO AS MICROCHIMERISM: a preexisting population of cells acquired during fetal life from her own mother, and newly acquired populations from her pregnancies. An intriguing question is whether the population of cells from her own mother can influence either maternal health during pregnancy and/or the next generation (grandchildren).
METHODOLOGY/PRINCIPAL FINDINGS: Microchimerism from a woman's (i.e. proband's) own mother (mother-of-the-proband, MP) was studied in peripheral blood samples from women followed longitudinally during pregnancy who were confirmed to have uncomplicated obstetric outcomes. Women with preeclampsia were studied at the time of diagnosis and comparison made to women with healthy pregnancies matched for parity and gestational age. Participants and family members were HLA-genotyped for DRB1, DQA1, and DQB1 loci. An HLA polymorphism unique to the woman's mother was identified, and a panel of HLA-specific quantitative PCR assays was employed to identify and quantify microchimerism. Microchimerism from the MP was identified during normal, uncomplicated pregnancy, with a peak concentration in the third trimester. The likelihood of detection increased with advancing gestational age. For each advancing trimester, there was a 12.7-fold increase in the probability of detecting microchimerism relative to the prior trimester, 95% confidence intervals 3.2, 50.3, p<0.001. None of the women with preeclampsia, compared with 30% of matched healthy women, had microchimerism (p = 0.03).
CONCLUSIONS/SIGNIFICANCE: These results show that microchimerism from a woman's own mother is detectable in normal pregnancy and diminished in preeclampsia, supporting the previously unexplored hypothesis that MP microchimerism may be a marker reflecting healthy maternal adaptation to pregnancy.
育龄妇女常携带少量的异体细胞,即微嵌合体:胎儿期从其自身母亲获得的预先存在的细胞群体,以及从妊娠中获得的新群体。一个有趣的问题是,她自身母亲的细胞群体是否会影响妊娠期间的母体健康和/或下一代(孙辈)。
方法/主要发现:对在妊娠期间接受纵向随访且确认有简单产科结局的妇女的外周血样本中,来自妇女自身母亲(即先证者的母亲,MP)的微嵌合体进行了研究。对患有子痫前期的妇女进行了研究,并与具有相同产次和孕龄的健康妊娠妇女进行了比较。参与者及其家庭成员进行了 HLA-DRB1、DQA1 和 DQB1 基因座的基因分型。确定了一种仅存在于妇女母亲的 HLA 多态性,并使用一组 HLA 特异性定量 PCR 检测来识别和量化微嵌合体。在正常、简单的妊娠期间发现了来自 MP 的微嵌合体,在孕晚期达到峰值浓度。随着妊娠的进展,检测到的可能性增加。对于每个妊娠晚期,与前一个妊娠晚期相比,检测到微嵌合体的概率增加了 12.7 倍,95%置信区间为 3.2、50.3,p<0.001。与 30%的匹配健康妇女相比,没有子痫前期的妇女中有微嵌合体(p=0.03)。
结论/意义:这些结果表明,来自妇女自身母亲的微嵌合体可在正常妊娠中检测到,并在子痫前期中减少,支持了先前未被探索的假说,即 MP 微嵌合体可能是反映母体健康适应妊娠的标志物。