Abstract
Worldwide, the Hepatitis E virus (HEV) is the main pathogen of acute viral hepatitis, with an extremely high mortality in pregnant women. However, the pathogenesis of HEV infection in pregnant women remains largely unknown. We established an HEV-infected pregnant mice animal model to explore the adverse pregnancy outcomes of HEV infection. Mice were infected with HEV in their early, middle and late stages of pregnancy. HEV RNA was detected in the tissues (liver, spleen, kidney, colon, uterus and placenta) of pregnant mice. HEV antigens were also detected in these tissues of HEV-infected pregnant mice. Miscarriages (7/8, 87.5%) occurred in pregnant mice infected with HEV in the middle of pregnancy. Th1-biased immune status was found in these aborted mice. Vertical transmission was confirmed by HEV replication in the uterus and placenta, as well as in the positive HEV RNA and HEV antigen positive in fetal livers. The successful establishment of HEV infection in pregnant mice is beneficial for further study of HEV pathogenesis, especially the adverse pregnancy outcomes caused by HEV infection.
Highlights
The relative expression of negative-strand Hepatitis E virus (HEV) RNA in the serum was compared among non-pregnant, normal delivery and miscarriage mice at 7 dpi in the early and middle pregnancy groups (Figure 2G)
Miscarriage and stillbirth were reported in pregnant women infected by genotype 1 and genotype 4 HEV [10,36]
Genotype 3 HEV infection was thought to be less-pathogenic in the maternal-fetal interface [7]
Summary
We established an HEV-infected pregnant mice animal model to explore the adverse pregnancy outcomes of HEV infection. Miscarriages (7/8, 87.5%) occurred in pregnant mice infected with HEV in the middle of pregnancy. The successful establishment of HEV infection in pregnant mice is beneficial for further study of HEV pathogenesis, especially the adverse pregnancy outcomes caused by HEV infection. 33.33% (8/24) of anti-HEV IgM positive pregnant women in China where the prevalent genotype 4 HEV has adverse pregnancy outcomes, including four threatened preterm births, three premature ruptures of membranes and one threatened abortion [10]. More severe pregnancy outcomes were reported in both anti-HEV IgM and IgG positive pregnant women with a 72.22% (13/18) occurrence of poor pregnancy outcomes, including 10 threatened preterm births, two premature ruptures of membranes and one threatened abortion [11].
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