Laboratory of Reproduction and Metabolism, CEFYBO-CONICET, School of Medicine, University of Buenos Aires, Argentina.
Reprod Toxicol. 2011 Dec;32(4):449-62. doi: 10.1016/j.reprotox.2011.09.003. Epub 2011 Sep 24.
Maternal diabetes increases the risks for embryo malformations. Matrix metalloproteinase-2 (MMP-2) and MMP-9 are two relevant MMPs for embryo development. Here, we addressed whether changes in these MMPs and in tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and TIMP-2 are altered in embryos and decidua from type 1 diabetic rats during early organogenesis. Our results demonstrate MMP-2 and MMP-9 overactivities and overexpression, together with increases in lipid peroxidation and nitric oxide production in embryos and decidua from diabetic animals. There is a concomitant increase in the inhibitory activity of TIMP-1 and TIMP-2 in embryos and decidua, and an increase in protein expression of embryonic TIMP-1 and TIMP-2. In situ zymography demonstrated MMPs overactivities despite increased TIMPs in embryos and decidua in maternal diabetes during early organogenesis. This study reveals that maternal diabetes leads to profound alterations in MMPs/TIMPs balance during embryo organogenesis, the gestational period during which most malformations are induced.
母体糖尿病增加胚胎畸形的风险。基质金属蛋白酶-2（MMP-2）和 MMP-9 是胚胎发育相关的两种重要 MMPs。在这里，我们研究了在早期器官发生期间，1 型糖尿病大鼠的胚胎和蜕膜中这些 MMPs 以及基质金属蛋白酶抑制剂-1（TIMP-1）和 TIMP-2 的变化是否发生改变。我们的结果表明，糖尿病动物的胚胎和蜕膜中 MMP-2 和 MMP-9 的活性和表达过度增加，同时伴随着脂质过氧化和一氧化氮产生的增加。胚胎和蜕膜中 TIMP-1 和 TIMP-2 的抑制活性也随之增加，胚胎中 TIMP-1 和 TIMP-2 的蛋白表达增加。原位酶谱分析表明，尽管在母体糖尿病期间胚胎和蜕膜中的 TIMPs 增加，但 MMPs 的活性仍过度增加。这项研究表明，母体糖尿病导致胚胎器官发生期间 MMPs/TIMPs 平衡发生深刻变化，这是大多数畸形发生的妊娠时期。
