Cyclosporin A improves murine pregnancy outcome in abortion-prone matings: involvement of CD80/86 and CD28/CTLA-4.
Cyclosporin A improves murine pregnancy outcome in abortion-prone matings: involvement of CD80/86 and CD28/CTLA-4.
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DOI：
10.1530/rep-07-0063
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发表时间：
2008-03
期刊：
影响因子：
3.8
通讯作者：
Wen-hui Zhou;Lin Dong;M. Du;Xiaoyong Zhu;Dajin Li
中科院分区：
文献类型：
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作者：
Wen-hui Zhou;Lin Dong;M. Du;Xiaoyong Zhu;Dajin Li
妊娠期间的免疫调节是复杂的，因此妊娠并发症的最佳治疗一直是生殖医学的一大挑战。环孢素A（CsA）是一种有效的免疫抑制剂，可预防同种异体移植物的排斥反应，但CsA对母胎关系的调节作用尚不清楚。在此，将与DBA/2雄性交配的怀孕CBA/J雌性作为流产倾向模型，在妊娠第4.5天给予CsA，并将与BALB/c雄性交配的怀孕CBA/J雌性作为成功妊娠对照。结果表明，CsA可显著上调CBA/J × DBA/2流产倾向小鼠着床窗CTLA-4的表达，下调CD80、CD86和CD28的表达，并显著降低流产倾向小鼠的胚胎吸收率。提示CsA对共刺激分子表达的调节可能有助于胎儿抵御母体免疫攻击。此外，CsA治疗诱导小鼠滋养层细胞的生长增强和细胞凋亡减少。总之，这些研究结果表明，CsA对流产倾向交配的母胎界面有有益的影响，从而改善妊娠结局，这可能为自发性妊娠浪费提供新的治疗方法。
Immune regulation during pregnancy is complex, and thus an optimal therapy for pregnancy complications is always a big challenge to reproductive medicine. Cyclosporin A (CsA), a potent immunosuppressant, prevents rejection of allografts by hosts, but little is known about the modulating effect of CsA on the materno-fetal relationship. Here, pregnant CBA/J females mated with DBA/2 males as an abortion-prone model were administered with CsA on day 4.5 of gestation, and the pregnant CBA/J females mated with BALB/c males were established as successful pregnancy control. It was demonstrated that administration of CsA at the window of implantation significantly up-regulated the expression of CTLA-4, while down-regulating the levels of CD80, CD86, and CD28 at the materno-fetal interface in the CBA/J x DBA/2 abortion-prone matings, and the embryo resorption rate of the abortion-prone matings reduced significantly after CsA treatment, implying that modulation of costimulatory molecule expression by CsA might contribute to preventing the fetus from maternal immune attack. In addition, treatment with CsA induced enhanced growth and reduced cell apoptosis of the murine trophoblast cells. Together, these findings indicate that CsA has a beneficial effect on the materno-fetal interface in abortion-prone matings, leading to a pregnancy outcome improvement, which might provide new therapeutics for spontaneous pregnancy wastage.