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

Viruses ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1950
Author(s):  
Weimin Yang ◽  
Shuangfeng Chen ◽  
Houfack K. Mickael ◽  
Liangheng Xu ◽  
Yueping Xia ◽  
...  
Keyword(s):  
Pregnancy Outcomes ◽  
Hepatitis E Virus ◽  
Inflammatory Responses ◽  
Hepatitis E ◽  
Adverse Pregnancy Outcomes ◽  
Vegf Expression ◽  
Genotype 4 ◽  
Infected Female ◽  
Expression Levels ◽  
Adverse Pregnancy

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.

scholarly journals Successful Establishment of Hepatitis E Virus Infection in Pregnant BALB/c Mice

Viruses ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 451 ◽  
Author(s):  
Chenchen Yang ◽  
Xianhui Hao ◽  
Yunlong Li ◽  
Feiyan Long ◽  
Qiuxia He ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Pregnancy Outcomes ◽  
Hepatitis E Virus ◽  
Acute Viral Hepatitis ◽  
Hepatitis E ◽  
Adverse Pregnancy Outcomes ◽  
Pregnant Mice ◽  
Successful Establishment ◽  
Adverse Pregnancy ◽  
Late Stages

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.

scholarly journals Vertical transmission of hepatitis E virus in pregnant rhesus macaques

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Wenhai Yu ◽  
Xianhui Hao ◽  
Yi Li ◽  
Chenchen Yang ◽  
Yunlong Li ◽  
...  
Keyword(s):  
Vertical Transmission ◽  
Hepatitis E Virus ◽  
Rhesus Macaques ◽  
Hepatitis E ◽  
Premature Delivery ◽  
Genotype 4 ◽  
Interferon Stimulated Genes ◽  
Elevated Liver Enzymes ◽  
Adverse Pregnancy ◽  
And Shifts

Abstract Hepatitis E virus (HEV) is the major pathogen of viral hepatitis. HEV causes high mortality in pregnant women. Its infection during pregnancy usually leads to fulminant hepatic failure, spontaneous abortions, premature delivery, or stillbirth. Vertical transmission of HEV has been reported, but the pathogenesis during pregnancy remains largely elusive. Pregnant rhesus macaques were infected with HEV to explore the pathogenesis of genotype 4 HEV infection during pregnancy. Active HEV infections were established with shedding viruses in the feces and blood, and elevated liver enzymes. Notably, higher viral titers and longer durations of HEV infection were found in HEV-infected pregnant rhesus macaques than in non-pregnant macaques. Premature delivery and fetal death occurred in one of the HEV-infected pregnant rhesus macaques. HEV RNA was detected in the liver, spleen, kidneys, and intestines of the dead fetus. This result strongly indicated vertical HEV transmission from mother to fetus. Maternal-transferred antibodies were observed in one of the babies with poor protection. The expressions of interferon-stimulated genes (ISGs) related to HEV infection were completely different between pregnant and non-pregnant rhesus macaques. During pregnancy, impaired innate immune responses, reduced progesterone levels, and shifts in immune states may aggravate HEV infection and result in adverse pregnancy outcomes.

scholarly journals Hepatitis E-related adverse pregnancy outcomes and their prevention by hepatitis E vaccine in a rabbit model

2019 ◽  
Vol 8 (1) ◽  
pp. 1066-1075 ◽  
Author(s):  
Manyu Li ◽  
Shuangshuang Li ◽  
Qiyu He ◽  
Zhaochao Liang ◽  
Lin Wang ◽  
...  
Keyword(s):  
Pregnancy Outcomes ◽  
Rabbit Model ◽  
Hepatitis E ◽  
Adverse Pregnancy Outcomes ◽  
Adverse Pregnancy

Association between Thiopurines Use and Pregnancy Outcomes in Female Patients with Inflammatory Bowel Disease: A Meta-analysis

2020 ◽  
Vol 26 ◽  
Author(s):  
Yang Zhang ◽  
Dandan Li ◽  
Heng Guo ◽  
Weina Wang ◽  
Xingang Li ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Preterm Birth ◽  
Spontaneous Abortion ◽  
Bowel Disease ◽  
Pregnancy Outcomes ◽  
Congenital Malformations ◽  
Meta Analysis ◽  
Adverse Pregnancy Outcomes ◽  
Inflammatory Bowel ◽  
Adverse Pregnancy

Background: Conflicting data exist regarding the influence of thiopurines exposure on adverse pregnancy outcomes in female patients with inflammatory bowel disease (IBD). Objective: The aim of this study was to provide an up-to-date and comprehensive assessment of the safety of thiopurines in pregnant IBD women. Methods: All relevant articles reporting pregnancy outcomes in women with IBD received thiopurines during pregnancy were identified from the databases (PubMed, Embase, Cochrane Library, and ClinicalTrials.gov) with the publication data up to April 2020. Data of included studies were extracted to calculate the relative risk (RR) of multiple pregnancy outcomes: congenital malformations, low birth weight (LBW), preterm birth, small for gestational age (SGA), and spontaneous abortion. The meta-analysis was performed using the random-effects model. Results: Eight studies matched with the inclusion criteria and a total of 1201 pregnant IBD women who used thiopurines and 4189 controls comprised of women with IBD received drugs other than thiopurines during pregnancy were included. Statistical analysis results demonstrated that the risk of preterm birth was significantly increased in the thiopurine-exposed group when compared to IBD controls (RR, 1.34; 95% CI, 1.00-1.79; p=0.049; I 2 =41%), while no statistically significant difference was observed in the incidence of other adverse pregnancy outcomes. Conclusion: Thiopurines’ use in women with IBD during pregnancy is not associated with congenital malformations, LBW, SGA, or spontaneous abortion, but appears to have an association with an increased risk of preterm birth.

The Need for Personalized Risk-Stratified Approaches to Treatment for Gestational Diabetes: A Narrative Review

2021 ◽  
Author(s):  
Shamil D. Cooray ◽  
Jacqueline A. Boyle ◽  
Georgia Soldatos ◽  
Shakila Thangaratinam ◽  
Helena J. Teede
Keyword(s):  
Gestational Diabetes ◽  
Pregnancy Outcomes ◽  
Population Based ◽  
Adverse Pregnancy Outcomes ◽  
Therapeutic Interventions ◽  
Clinical Prediction Model ◽  
Increased Risk ◽  
Adverse Pregnancy ◽  
The Individual ◽  
Personalized Risk

AbstractGestational diabetes mellitus (GDM) is common and is associated with an increased risk of adverse pregnancy outcomes. However, the prevailing one-size-fits-all approach that treats all women with GDM as having equivalent risk needs revision, given the clinical heterogeneity of GDM, the limitations of a population-based approach to risk, and the need to move beyond a glucocentric focus to address other intersecting risk factors. To address these challenges, we propose using a clinical prediction model for adverse pregnancy outcomes to guide risk-stratified approaches to treatment tailored to the individual needs of women with GDM. This will allow preventative and therapeutic interventions to be delivered to those who will maximally benefit, sparing expense, and harm for those at a lower risk.

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