Garcia Mariana G, Tirado-Gonzalez Irene, Handjiski Bori, Tometten Mareike, Orsal Arif S, Hajos Silvia E, Fernández Nelson, Arck Petra C, Blois Sandra M
Charité, Medicine University of Berlin, Biomedical Research Building (BMFZ), Raum 2.0549, Campus Virchow, Augustenburger Platz 1, 13353 Berlin, Germany.
Placenta. 2007 Jul;28(7):650-7. doi: 10.1016/j.placenta.2006.09.010. Epub 2006 Nov 16.
The materno-fetal interface has for long been considered as an immune privileged biological site and thus understanding the mechanisms underlying fetal survival have been the focus of intense research. In adults, survivin and Stat-3 proteins are involved in tolerance as well as the induction of apoptosis. However, the role of these molecules in pregnancy and development has not been addressed. We have evaluated the expression of survivin and Stat-3 in allogeneic mouse models of low abortions (CBA/J x Balb/c), abortion prone (CBA/J x DBA/2J) and stress-triggered abortions from DBA/2J-mated CBA/J mice. We show that survivin is over-expressed in abortion-prone mating on gestation day 7.5. This effect was also found in stress-exposed mice, whereas expression was low in normal pregnancy mice. The phosphorylated Stat-3 (p-Stat-3) was down regulated in high abortion mating compared with low abortion mating, CBA/J x Balb/c. The level of apoptosis was similar in the three groups studied. Our results suggest that high expression of survivin and low expression of p-Stat-3 are involved in pregnancy loss in mice.
母胎界面长期以来一直被视为一个免疫特惠生物学部位,因此了解胎儿存活的潜在机制一直是深入研究的重点。在成年人中,生存素和信号转导与转录激活因子3(Stat-3)蛋白参与免疫耐受以及细胞凋亡的诱导。然而,这些分子在妊娠和发育中的作用尚未得到研究。我们评估了低流产率(CBA/J×Balb/c)、易流产(CBA/J×DBA/2J)以及DBA/2J与CBA/J交配产生的应激诱导流产的同种异体小鼠模型中生存素和Stat-3的表达。我们发现,在妊娠第7.5天,易流产交配中生存素过度表达。在应激暴露小鼠中也发现了这种效应,而正常妊娠小鼠中的表达较低。与低流产率交配(CBA/J×Balb/c)相比,高流产率交配中磷酸化Stat-3(p-Stat-3)下调。研究的三组中细胞凋亡水平相似。我们的结果表明,生存素的高表达和p-Stat-3的低表达与小鼠妊娠丢失有关。