Department of Obsterics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Virol J. 2011 Mar 11;8:114. doi: 10.1186/1743-422X-8-114.
Human cytomegalovirus (HCMV) is the most common pathogen in uterus during pregnancy, which may lead to some serious results such as miscarriage, stillbirth, cerebellar malformation, fetus developmental retardation, but its pathogenesis has not been fully explained. The hypofunction of extravillous cytotrophoblast (EVT) invasion is the essential pathologic base of some complications of pregnancy. c-erbB-2 is a kind of oncogene protein and closely linked with embryogenesis, tissue repair and regeneration. Matrix metalloproteinase (MMP) is one of the key enzymes which affect EVT migration and invasion function. The expression level changes of c-erbB-2, MMP-2 and MMP-9 can reflect the changes of EVT invasion function.
To explore the influence of HCMV on the invasion function of EVT, we tested the protein expression level changes of c-erbB-2, MMP-2 and MMP-9 in villous explant cultured in vitro infected by HCMV, with the use of immunohistochemistry SP method and western blot. We confirmed that HCMV can reproduce and spread in early pregnancy villus; c-erbB-2 protein mainly expressed in normal early pregnancy villous syncytiotrophoblast (ST) remote plasma membrane and EVT, especially remote EVT cell membrane in villous stem cell column, little expressed in ST proximal end cell membrane and interstitial cells; MMP-2 protein primarily expressed in early pregnancy villous EVT endochylema and rarely in villous trophoblast (VT), ST and interstitial cells; MMP-9 protein largely expressed in early pregnancy villous mesenchyme, EVT and VT endochylema. Compared with control group, the three kinds of protein expression level in early pregnancy villus of virus group significantly decreased (P < 0.05).
HCMV can infect villus in vitro and cause the decrease of early pregnancy villous EVT's invasion function.
人巨细胞病毒(HCMV)是妊娠子宫中最常见的病原体,可能导致一些严重后果,如流产、死产、小脑畸形、胎儿发育迟缓,但其发病机制尚未完全阐明。绒毛外滋养细胞(EVT)侵入功能不全是妊娠某些并发症的基本病理基础。c-erbB-2 是一种癌基因蛋白,与胚胎发生、组织修复和再生密切相关。基质金属蛋白酶(MMP)是影响 EVT 迁移和侵袭功能的关键酶之一。c-erbB-2、MMP-2 和 MMP-9 的表达水平变化可以反映 EVT 侵袭功能的变化。
为了探讨 HCMV 对 EVT 侵袭功能的影响,我们采用免疫组化 SP 法和 Western blot 法检测了体外感染 HCMV 的绒毛外植体中 c-erbB-2、MMP-2 和 MMP-9 的蛋白表达水平变化。我们证实 HCMV 可在早孕绒毛中复制和扩散;c-erbB-2 蛋白主要表达于正常早孕绒毛合体滋养层(ST)远侧质膜和 EVT,尤其是绒毛干细胞柱中 EVT 远侧细胞膜,ST 近侧质膜和间质细胞中表达较少;MMP-2 蛋白主要表达于早孕绒毛 EVT 胞质,绒毛滋养层(VT)、ST 和间质细胞中表达较少;MMP-9 蛋白主要表达于早孕绒毛间质,EVT 和 VT 胞质中表达较多。与对照组相比,病毒组早孕绒毛中这三种蛋白的表达水平均显著降低(P<0.05)。
HCMV 可感染体外绒毛,并导致早孕绒毛 EVT 侵袭功能下降。