Uterine natural killer cells and angiogenesis in recurrent reproductive failure
Uterine natural killer cells and angiogenesis in recurrent reproductive failure
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DOI：
10.1093/humrep/den348
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发表时间：
2009-01-01
影响因子：
6.1
通讯作者：
Bulmer, Judith
中科院分区：
文献类型：
--
作者：
Quenby, Siobhan;Nik, Helena;Bulmer, Judith
表型异常的CD56(明亮)CD16-子宫自然杀伤(Unk)细胞的数量增加与复发性生殖失败有关。UNK细胞产生血管生成生长因子，是早孕蜕膜血管生成的潜在调节因子。早期妊娠丢失的最终常见机制被认为是母体循环过早开始和胎盘过度氧化应激。我们验证了这样的假设，即植入前子宫内膜中Unk细胞的增加与血管生成的改变有关。对122例反复生育失败的妇女进行了子宫动脉多普勒和子宫内膜活检。UNK细胞密度与血管形成(P=0.005.0 5，r=0.5)、淋巴管形成(P=0.0001，r=0.6)、螺旋小动脉平滑肌分化(P=0.0 1，r=0.5)、子宫内膜水肿(P=0.004)呈正相关。这些数据表明，Unk细胞可能调节非妊娠子宫内膜的血管生成。与Unk细胞密度增加相关的生殖失败的机制似乎是血管生成和围着床期血流增加，这可能导致早期母体循环，从而由于过度的氧化应激而导致妊娠失败。
Increased numbers of phenotypically unusual CD56(bright) CD16- uterine natural killer (uNK) cells have been associated with recurrent reproductive failure. uNK cells produce angiogenic growth factors and are potential regulators of decidual angiogenesis in early pregnancy. The final common mechanism for early pregnancy loss is thought to be early onset of the maternal circulation and excessive placental oxidative stress. We tested the hypothesis that increased uNK cells in preimplantation endometrium are associated with altered angiogenesis.Women with recurrent reproductive failure (n = 122) were investigated with uterine artery Doppler and endometrial biopsy. Immunohistochemistry was used to identify uNK, endothelial and vascular smooth muscle cells and image analysis was used to assess location, density and differentiation.uNK cell density was positively correlated with the formation of blood (P = 0.005, r = 0.5) and lymphatic vessels (P = 0.0001, r = 0.6), spiral arteriole smooth muscle differentiation (P = 0.01, r = 0.5) and endometrial oedema (P = 0.004). The functional effect of this was a reduced uterine artery resistance to blood flow.These data suggest that uNK cells may regulate angiogenesis in non-pregnant endometrium. The mechanisms of reproductive failure associated with increased uNK cell density appear to be increased angiogenesis and peri-implantation blood flow, which may lead to early maternal circulation and hence pregnancy failure due to excessive oxidative stress.