In vitro study on human cytomegalovirus affecting early pregnancy villous EVT's invasion function

Liu Tao,Chen Juanjuan,Xiao Juan,Yin Zongzhi,Chen Suhua,Zhang Dandan

doi:10.1186/1743-422x-8-114

Abstract

BackgroundHuman 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.ResultsTo 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).ConclusionHCMV can infect villus in vitro and cause the decrease of early pregnancy villous EVT's invasion function.

Highlights

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]
When infected group was added into HCMV and cultured for 48 h, HCMVpp65 signals showed almost all CT, extravillous cytotrophoblast (EVT), ST, interstitial cells and around villous interstitial substance small blood vessels in villus (Figure 2B), while there was no HCMVpp65 antigen signal in control group(Figure 2A)
HCMV was added into early pregnancy villus in vitro culture, after 48 h, which can cause villus infection

Summary

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). 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. 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. Matrix metalloproteinase (MMP) is one of the key enzymes which affect EVT migration and invasion function. The expression level changes of c-erbB2, MMP-2 and MMP-9 can reflect the changes of EVT invasion function

Methods

Results

Discussion

Conclusion