Chamley L W, Holland O J, Chen Q, Viall C A, Stone P R, Abumaree M
Department of Obstetrics and Gynaecology, The University of Auckland, Auckland, New Zealand; Gravida the National Centre for Growth and Development, Auckland, New Zealand.
Department of Obstetrics and Gynaecology, The University of Auckland, Auckland, New Zealand.
Placenta. 2014 Feb;35 Suppl:S74-80. doi: 10.1016/j.placenta.2013.10.014. Epub 2013 Nov 4.
Ask where the maternofetal interface is and placental biologists will tell you, the syncytiotrophoblast and extravillous cytotrophoblasts. While correct, this is not full extent of the maternofetal interface. Trophoblast debris that is extruded into the maternal blood in all pregnancies expands the maternofetal interface to sites remote from the uterus. Trophoblast debris ranges from multinucleated syncytial nuclear aggregates to subcellular micro- and nano-vesicles. The origins of trophoblast debris are not clear. Some propose trophoblast debris is the end of the life-cycle of the trophoblast and that it results from an apoptosis-like cell death, but this is not universally accepted. Knowing whether trophoblast debris results from an apoptosis-like cell death is important because the nature of cell death that produced trophoblast debris will influence the maternal responses to it. Trophoblast debris is challenging to isolate from maternal blood making it difficult to study. However, by culturing placental explants in Netwells™ we can readily harvest trophoblast debris from beneath the Netwells™ which is very similar to debris that has been isolated from pregnant women. We have found that trophoblast debris from normal placentae shows markers of apoptosis and is phagocytosed by macrophages or endothelial cells, producing a tolerant phenotype in the phagocyte. Whereas, when we culture normal placental explants with factors such as antiphospholipid antibodies (a strong maternal risk factor for preeclampsia), or IL-6 (which is found at increased levels in the sera of preeclamptic women), the death process in the syncytiotrophoblast changes, such that the trophoblast debris becomes more necrotic. Phagocytosis of this necrotic debris leads to activation of endothelial cells. Trophoblast debris greatly expands the maternofetal interface and the nature of that debris is likely to strongly influence the responses of the maternal vascular and immune systems to the debris.
问起母胎界面在哪里，胎盘生物学家会告诉你，是合体滋养层细胞和绒毛外细胞滋养层细胞。虽然没错，但这并非母胎界面的全部范围。在所有妊娠中，被挤出进入母体血液的滋养层碎片将母胎界面扩展到了子宫以外的部位。滋养层碎片包括多核合体细胞核聚集体以及亚细胞微泡和纳米囊泡。滋养层碎片的来源尚不清楚。有人提出滋养层碎片是滋养层细胞生命周期的终点，是由类似凋亡的细胞死亡导致的，但这一观点并未得到普遍认可。了解滋养层碎片是否由类似凋亡的细胞死亡导致很重要，因为产生滋养层碎片的细胞死亡性质会影响母体对它的反应。从母体血液中分离滋养层碎片具有挑战性，这使得研究工作困难重重。然而，通过在微孔板中培养胎盘外植体，我们可以轻松地从微孔板下方收获滋养层碎片，这些碎片与从孕妇体内分离出的碎片非常相似。我们发现，正常胎盘的滋养层碎片显示出凋亡标记，会被巨噬细胞或内皮细胞吞噬，从而在吞噬细胞中产生耐受表型。而当我们用抗磷脂抗体（子痫前期的一个强大母体风险因素）或白细胞介素 - 6（子痫前期女性血清中水平升高）等因子培养正常胎盘外植体时，合体滋养层细胞的死亡过程会发生变化，使得滋养层碎片变得更具坏死性。吞噬这种坏死碎片会导致内皮细胞活化。滋养层碎片极大地扩展了母胎界面，其性质可能会强烈影响母体血管和免疫系统对碎片的反应。
