Lack of human leukocyte antigen-G expression in extravillous trophoblasts is associated with pre-eclampsia

Lack of human leukocyte antigen-G expression in extravillous trophoblasts is associated with pre-eclampsia
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DOI:
10.1093/molehr/6.1.88
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发表时间:
2000-01-01
影响因子:
4
通讯作者:
Yagel, S
Yagel, S
中科院分区:
医学2区
文献类型:
--
作者:
Goldman-Wohl, DS;Ariel, I;Yagel, S

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先兆子痫是首次妊娠的常见并发症,被认为是由于胎盘灌注不良,可能反映了母体对半同种异体胎儿的异常免疫反应。人类白细胞抗原(HLA)-G是一种主要的组织相容性组织特异性抗原,在绒毛外滋养层细胞(胎儿来源)中表达,可保护滋养层细胞免受母胎免疫不耐受的影响,并使这些细胞侵入子宫。本研究通过RNA原位杂交技术,对HLA-G在正常胎盘和重度子痫前期患者胎盘组织中的表达进行了研究。在正常胎盘中,我们发现HLA-G在绒毛外滋养细胞中表达,在侵袭性细胞中表达梯度增加。然而,在10个先兆子痫胎盘HLA-G表达的9个是不存在或减少。我们的结论是,HLA-G是正常表达的浸润性滋养细胞和HLA-G的表达是有缺陷的,在大多数先兆子痫胎盘。我们认为缺乏HLA-G的滋养层细胞容易受到母体免疫系统的攻击。这些有缺陷的滋养层将不能有效地侵入母体螺旋动脉,从而发育出不能充分滋养发育中的胎盘的血管。这种灌注不良的胎盘可能引发与先兆子痫相关的全身级联反应。
Pre-eclampsia, a common complication of first pregnancies, is thought to result from a poorly perfused placenta and may reflect an abnormal maternal immune reaction to the hemiallogenic fetus. Human leukocyte antigen (HLA)-G, a major histocompatibility tissue-specific antigen expressed in extravillous trophoblast cells (fetal-derived), may protect trophoblasts from maternal-fetal immune intolerance and allow these cells to invade the uterus. Through RNA in-situ hybridization analysis, we studied the expression pattern of HLA-G in normal placentae and placentae from pregnancies complicated by severe pre-eclampsia. In normal placenta we found HLA-G expression in the anchoring extravillous trophoblasts with an increasing gradient of expression in the more invasive cells. However, in nine out of 10 pre-eclamptic placentae HLA-G expression was absent or reduced. We conclude that HLA-G is normally expressed in invasive trophoblasts and HLA-G expression is defective in most pre-eclamptic placentae. We propose that trophoblasts lacking HLA-G are vulnerable to attack by the maternal immune system. These defective trophoblasts will be unable to invade the maternal spiral arteries effectively, thereby developing vessels which cannot adequately nourish the developing placenta. This poorly perfused placenta may initiate the systemic cascade of events associated with pre-eclampsia.