Background
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.
Results
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).
Conclusion
HCMV can infect villus in vitro and cause the decrease of early pregnancy villous EVT’s invasion function.
Introduction
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[1]. It is currently considered that in later stage of blastula’s nidation, cytotrophoblast (CT) differentiates to villous trophoblast (VT) and extravillous cytotrophoblast (EVT). VT is active in karyokinesis, fusing to form syncytiotrophoblast (ST). ST performs the functions of internal secretion, immunity and material exchange and so on; EVT forms cell column after its proliferation and migration, invasively grow towards uterus mesenchyme and spiral artery lumen, rebuilding spiral artery[2]. The hypofunction of EVT invasion is the essential pathologic base of miscarriage, premature birth, stillbirth, fetus developmental retardation, gestational hypertension and other complications of pregnancy[3]. As being one of the symbolic proteins of EVT, c-erbB-2 protein participates in the process of EVT invasion[4]. In addition, Matrix metalloproteinase (MMP) is one of the key enzymes which affect EVT migration and invasion function, especially MMP-2 and MMP-9. At present, there are only a few studies on HCMV’s influence on EVT invasion function. In order to explore the correlation of EVT invasion dysfunction and HCMV intrauterine infection which causes miscarriage, stillbirth and fetus developmental retardation, this paper adopts early pregnancy villous explant cultured in vitro, so as to observe HCMV’s influence on EVT invasion function in villus.