Molecular mechanisms of Zika virus teratogenesis from animal studies: a systematic review protocol
Gabriela Elis Wachholz1,2,3, Julia do Amaral Gomes1,2,3, Juliano André Boquett1,4
1Graduate Program in Genetics and Molecular Biology, Department of Genetics, Biosciences Institute, Universidade Federal do Rio Grande do Sul, Porto Alegre, 91501-970, Brazil.
Background:
Due to the diversity of studies in animal models reporting that molecular mechanisms are involved in the teratogenic effect of the Zika virus (ZIKV), the objective of the present study is to evaluate the methodological quality of these studies, as well as to demonstrate which genes and which molecular pathways are affected by ZIKV in different animal models.
Methods:
This search will be performed in four databases: PubMed/MEDLINE, EMBASE, Web of Science, and Scopus, as well as in the grey literature. The studies selection process will be reported through the PRISMA Statement diagram model. All studies describing the molecular mechanisms possibly involved in the development of malformations caused by embryonic/fetal ZIKV exposure in animal models with an appropriate control group and methodology will be included (including, for instance, randomized and non-randomized studies). All animals used as experimental models for ZIKV teratogenesis may be included as long as exposure to the virus occurred during the embryonic/fetal period. From the selected studies, data will be extracted using a previously prepared standard form. Bias risk evaluation will be conducted following the SYRCLE's Risk of Bias tool. All data obtained will be tabulated and organized by outcomes (morphological and molecular).
Discussion:
With the proposed systematic review, we expect to present results about the methodological quality of the published studies with animal models that investigated the molecular mechanisms involved in the teratogenic effect of ZIKV, as well as to show the studies with greater reliability.
Systematic Review Registration:
PROSPERO CRD42019157316.
Insights
This systematic review assesses studies on Zika virus (ZIKV) teratogenesis in animal models. It evaluates methodological quality and identifies affected genes and molecular pathways, aiming to highlight reliable research on ZIKV
Area of Science:
- Virology
- Teratology
- Molecular Biology
- Systematic Review Methodology
Background:
- Numerous studies in animal models suggest molecular mechanisms underlie Zika virus (ZIKV) teratogenic effects.
- Understanding these mechanisms is crucial for developing interventions against ZIKV-induced congenital abnormalities.
- A critical evaluation of existing research quality is needed to identify reliable findings.
Purpose of the Study:
- To systematically evaluate the methodological quality of studies investigating ZIKV teratogenesis in animal models.
- To identify specific genes and molecular pathways affected by ZIKV exposure during embryonic/fetal development.
- To determine the reliability of current research on ZIKV's molecular teratogenic effects.
Main Methods:
- Comprehensive literature search across PubMed/MEDLINE, EMBASE, Web of Science, and Scopus, including grey literature.
- Study selection based on PRISMA guidelines, including animal models with ZIKV exposure during embryonic/fetal periods and control groups.
- Methodological quality assessment using SYRCLE's Risk of Bias tool, with data extraction and tabulation by morphological and molecular outcomes.
Main Results:
- The review will present findings on the methodological rigor of published studies.
- It will identify and summarize molecular targets and pathways implicated in ZIKV-induced teratogenesis.
- Reliable studies demonstrating significant molecular alterations will be highlighted.
Conclusions:
- This systematic review will provide a critical assessment of the quality of evidence regarding ZIKV's molecular teratogenic effects in animal models.
- The findings will consolidate knowledge on affected genes and pathways, guiding future research.
- Identifying high-quality studies will enhance confidence in the understanding of ZIKV's developmental toxicity.


