Department of Obstetrics and Gynecology, Nagoya City University, Graduate School of Medical Sciences, One Kawasumi, Mizuho-ku, Aichi, Nagoya 467-8601, Japan.
Department of Obstetrics and Gynecology, Nagoya City University, Graduate School of Medical Sciences, One Kawasumi, Mizuho-ku, Aichi, Nagoya 467-8601, Japan; Department of Obstetrics and Gynecology, Nagoya City University West Medical Center, 1-1-1 Hirate-cho, Kita-ku, Aichi, Nagoya 462-8508, Japan.
J Reprod Immunol. 2024 Aug;164:104270. doi: 10.1016/j.jri.2024.104270. Epub 2024 May 26.
Matrix metalloproteinases (MMPs) degrade extracellular matrix proteins and are important for placenta formation during early pregnancy. Recurrent pregnancy loss (RPL) is associated with abnormalities in endometrial extracellular matrix remodeling. This study aimed to elucidate the roles of MMP2 and MMP9 in RPL pathogenesis. In total, 295 women with a history of RPL and 101 controls were included in this genetic study. Genotype analysis was performed using polymerase chain reaction (PCR) restriction fragment length polymorphisms. For proteolytic analysis, decidua and villi were collected from 10 RPL-miscarried women with normal fetal chromosomes (NC) and 19 women with fetal chromosome aberrations (AC). The expression of MMP2 and MMP9 in the decidua and villi was measured by IHC and ELISA. All samples were collected after obtaining informed consent. There were no statistically significant differences in MMP2-735 C/T and MMP9-1562 C/T frequencies between women with RPL and the controls. There was no significant difference in MMP2 expression levels in the villi; however, MMP9 expression was significantly higher in normal fetal chromosomes. In the decidua, the expression of MMP2 in the NC group was significantly lower, and MMP9 in the NC group was significantly higher than in the AC group. Although no differences in MMP2-735 C/T and MMP9-1562 C/T gene polymorphisms were observed in the present study, it is suggested that differences at the protein level are involved in the pathogenesis of RPL since MMP expression is not only regulated by genes but also by local inflammation and various inductive signals.
基质金属蛋白酶（MMPs）降解细胞外基质蛋白，在妊娠早期对于胎盘形成非常重要。复发性流产（RPL）与子宫内膜细胞外基质重塑异常有关。本研究旨在阐明 MMP2 和 MMP9 在 RPL 发病机制中的作用。共有 295 名有 RPL 病史的妇女和 101 名对照者纳入本项遗传研究。采用聚合酶链反应（PCR）限制性片段长度多态性进行基因型分析。为了进行蛋白水解分析，从 10 名 RPL 流产且胎儿染色体正常（NC）和 19 名胎儿染色体异常（AC）的妇女中收集了蜕膜和绒毛组织。采用免疫组化和 ELISA 法测量 MMP2 和 MMP9 在蜕膜和绒毛中的表达。所有样本均在获得知情同意后采集。RPL 患者与对照组之间 MMP2-735 C/T 和 MMP9-1562 C/T 频率无统计学差异。绒毛中 MMP2 表达水平无显著差异，而 MMP9 在正常胎儿染色体中表达显著升高。在蜕膜中，NC 组 MMP2 表达显著降低，而 MMP9 在 NC 组中显著高于 AC 组。虽然本研究未观察到 MMP2-735 C/T 和 MMP9-1562 C/T 基因多态性的差异，但由于 MMP 表达不仅受基因调控，还受局部炎症和各种诱导信号的影响，因此提示蛋白水平的差异可能与 RPL 的发病机制有关。
