Placental bed research: II. Functional and immunological investigations of the placental bed
Placental bed research: II. Functional and immunological investigations of the placental bed
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DOI：
10.1016/j.ajog.2019.07.010
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发表时间：
2019-11-01
影响因子：
9.8
通讯作者：
Benagiano, Giuseppe
中科院分区：
文献类型：
--
作者：
Harris, Lynda K.;Benagiano, Marisa;Benagiano, Giuseppe
胎盘作为母亲和胎儿之间的界面的研究已经进行了大约150年，在随后的2篇综述中，我们试图总结这种情况。在第一部分中，我们描述了子宫胎盘螺旋动脉独特的生理变化的发现，使他们能够科普血流量的大幅增加，以确保胎儿的正常生长。这些包括滋养层细胞对动脉壁的侵入及其正常结构的逐渐消失。研究人员随后转向胎盘床的病理生理学，特别是其母体血管树。这为更好地了解所谓的重大产科综合征（先兆子痫、胎儿生长受限、早产和分娩、胎盘植入）提供了重要信息。子宫胎盘血管系统的形态学研究表明，先兆子痫与螺旋动脉的转化减少或失败以及子宫肌层部分的内皮细胞和平滑肌细胞的持续存在有关。在这里，我们报告最近的胎盘床的功能调查，包括子宫胎盘血流和血管阻力的原位生物物理研究，和子宫胎盘灌注的操作。这些新方法提供了一种新的方法来识别重塑受损的妊娠。在动物中，现在可以操纵子宫胎盘血流，从而促进胎儿生长;这为在异常人类妊娠中进行试验开辟了道路。在第二部分，我们探索了一个新的，非常重要的研究领域，涉及胎盘床中白细胞和巨噬细胞的特定亚群的作用。人类妊娠早期的蜕膜富含白细胞，称为子宫自然杀伤细胞。巨噬细胞和子宫自然杀伤细胞从分泌期子宫内膜到妊娠早期数量增加，并通过诱导初始结构变化在介导螺旋动脉转化过程中发挥关键作用。因此，螺旋动脉的血管重塑似乎是独立于滋养层细胞入侵而启动的。免疫系统的失调可能导致生殖失败或妊娠并发症，在这方面，最近的研究已经推进了我们对妊娠期间免疫耐受调节机制的理解，提出了几种机制用于半同种异体胎儿耐受的发展。特别是，这些包括滋养层避免母体识别的几种策略。最后，正在探索一个重要的新维度：妊娠综合征和子宫胎盘血管重塑受损可能与未来母亲甚至儿童的心血管疾病风险有关。这些意见的功能证据将进行讨论。
Research on the placenta as the interface between the mother and the fetus has been undertaken for some 150 years, and in 2 subsequent reviews, we attempted to summarize the situation. In the first part, we described the discovery of unique physiological modifications of the uteroplacental spiral arteries, enabling them to cope with a major increase in blood flow necessary to ensure proper growth of the fetus. These consist of an invasion of the arterial walls by trophoblast and a progressive disappearance of its normal structure. Researchers then turned to the pathophysiology of the placental bed and in particular to its maternal vascular tree. This yielded vital information for a better understanding of the so-called great obstetrical syndromes (preeclampsia, fetal growth restriction, premature labor and delivery, placenta accreta). Systematic morphological investigations of the uteroplacental vasculature showed that preeclampsia is associated with decreased or failed transformation of spiral arteries and the persistence of endothelial and smooth muscle cells in segments of their myometrial portion. Here we report on recent functional investigations of the placental bed, including in situ biophysical studies of uteroplacental blood flow and vascular resistance, and manipulation of uteroplacental perfusion. These new methodologies have provided a novel way of identifying pregnancies in which remodeling is impaired. In animals it is now possible to manipulate uteroplacental blood flow, leading to an enhancement of fetal growth; this opens the way to trials in abnormal human pregnancies. In this second part, we explored a new, extremely important area of research that deals with the role of specific subsets of leukocytes and macrophages in the placental bed. The human first-trimester decidua is rich in leukocytes called uterine natural killer cells. Both macrophages and uterine natural killer cells increase in number from the secretory endometrium to early pregnancy and play a critical role in mediating the process of spiral artery transformation by inducing initial structural changes. It seems therefore that vascular remodeling of spiral arteries is initiated independently of trophoblast invasion. Dysregulation of the immune system may lead to reproductive failure or pregnancy complications, and in this respect, recent studies have advanced our understanding of the mechanisms regulating immunological tolerance during pregnancy, with several mechanisms being proposed for the development of tolerance to the semiallogeneic fetus. In particular, these include several strategies by which the trophoblast avoids maternal recognition. Finally, an important new dimension is being explored: the likelihood that pregnancy syndromes and impaired uteroplacental vascular remodeling may be linked to future maternal and even the child's cardiovascular disease risk. The functional evidence underlying these observations will be discussed.