Uterine Injury Caused by Genotype 4 Hepatitis E Virus Infection Based on a BALB/c Mice Model

• Published in: Viruses Vol. 13; no. 10; p. 1950
• Main Authors: Yang, Weimin, Chen, Shuangfeng, Mickael, Houfack K, Xu, Liangheng, Xia, Yueping, Cong, Chao, Zhang, Yike, Qian, Zhongyao, Li, Tengyuan, Wei, Daqiao, Yu, Wenhai, Huang, Fen
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 28.09.2021; MDPI
• Subjects: Abortion, Spontaneous; Animals; Antibodies; Antigens; Apoptosis; Cell culture; Copulation; Cytokeratin; Cytokines; Disease Models, Animal; Endometrium; Estrogen receptors; Estrogens; Female; Genotype; Genotype & phenotype; Genotypes; Hepatitis; Hepatitis Antibodies - immunology; Hepatitis E - complications; Hepatitis E - virology; hepatitis E virus; Hepatitis E virus - classification; Hepatitis E virus - genetics; Hepatitis E virus - pathogenicity; Infections; Infertility; Inflammation; Male; Maternal mortality; Mice; Mice, Inbred BALB C; Miscarriage; Pathogenesis; Pathogens; Pregnancy; Pregnancy Outcome; Premature birth; Stillbirth; Urogenital Abnormalities - virology; uterine injury; Uterus; Uterus - abnormalities; Uterus - injuries; Uterus - pathology; Uterus - virology; Vascular endothelial growth factor; Vimentin; Viral infections; Virus Shedding; Viruses; Womens health; United States > US; China; Japan; hepatitis E virus; miscarriage; pregnancy; uterine injury
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v13101950

To evaluate whether uterine injury caused by hepatitis E virus (HEV) infection is responsible for adverse pregnancy outcomes. HEV-infected female BALB/c mice were coupled with healthy male BALB/c mice at 0, 7, 14, 21, and 91 dpi to explore the uterine injury caused by HEV infection. Mice were euthanized after 10 days of copulation, and uteruses were collected for HEV RNA and antigen detection and histopathological analysis. Inflammatory responses; apoptosis; and estrogen receptor ɑ (ER-ɑ), endomethal antibody (ERAb), cytokeratin-7 (CK7), vimentin (VIM), and vascular endothelial growth factor (VEGF) expression levels were evaluated. After 10 days of copulation, miscarriage and nonpregnancy, as well as enlarged uteruses filled with inflammatory cytokines, were found in HEV-infected mice. HEV RNA and antigens were detected in the sera and uteruses of HEV-infected mice. Significant endometrial thickness (EMT) thinning, severe inflammatory responses, and aggravated apoptosis in the uteruses of HEV-infected mice that experienced miscarriage might contribute to adverse pregnancy outcomes. Furthermore, significantly suppressed ER-ɑ expression and increased ERAb, CK7, VIM, and VEGF expression levels were found in the uteruses of HEV-infected mice that had miscarried. However, uterine damage recovered after complete HEV clearance, and impaired fertility was improved. EMT injury, severe inflammatory responses, and aggravated apoptosis in the uterus caused by HEV infection are responsible for poor pregnancy outcomes.