Corticotropin-releasing hormone promotes blastocyst implantation and early maternal tolerance
Corticotropin-releasing hormone promotes blastocyst implantation and early maternal tolerance
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DOI：
10.1038/ni719
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发表时间：
2001-11-01
影响因子：
30.5
通讯作者：
Chrousos, GP
中科院分区：
文献类型：
--
作者：
Makrigiannakis, A;Zoumakis, E;Chrousos, GP
囊胚阶段的半同种异体移植胚胎将自身植入子宫内膜，但没有激活免疫排斥过程。胚胎滋养层和母体蜕膜产生促肾上腺皮质激素释放激素 (CRH) 并表达 Fas 配体 (FasL)（一种促凋亡细胞因子）。我们发现 antalarmin（一种 CRH 受体 I 型拮抗剂）可降低 FasL 表达并促进活化的 T 淋巴细胞凋亡，该作用可被 CRH 增强并被 antalarmin 抑制。用antalarmin治疗的雌性大鼠显示着床位点和活胚胎显着减少，子宫内膜FasL表达减少。当母亲服用安塔拉明时，缺乏 T 细胞的母亲或同基因交配的胚胎不会被排斥。这些发现表明，本地产生的 CRH 主要通过杀死活化的 T 细胞来促进早期妊娠的着床和维持。
The semi-allograft embryo in the blastocyst stage implants itself in the endometrium, yet no immune rejection processes are activated. Embryonic trophoblast and maternal decidua produce corticotropin-releasing hormone (CRH) and express Fas ligand (FasL), a proapoptotic cytokine. We found that antalarmin, a CRH receptor type I antagonist, decreased FasL expression and promoted apoptosis of activated T lymphocytes, an effect which was potentiated by CRH and inhibited by antalarmin. Female rats treated with antalarmin showed a marked decrease in implantation sites and live embryos and diminished endometrial FasL expression. Embryos from mothers that lacked T cells or from syngeneic matings were not rejected when the mothers were given antalarmin. These findings suggested that locally produced CRH promotes implantation and maintenance of early pregnancy primarily by killing activated T cells.