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. 2022 Oct 10;60(1):68–83. doi: 10.1007/s12035-022-03046-4

Table 2.

Main characteristics related to morphological analysis

Study ID Sample size Outcome evaluation method Embryo age at morphological outcome evaluation Main teratogenic finding Evaluated organs
Li et al., 2016 [18] Not mentioned Histological evaluation of brain slices, including Immunohistochemistry and Nissl staining and confocal imaging 3dpi (E16.5) and 5dpi (E18.5) Thinner cortex and microcephaly Brain
Shao et al., 2016 [32] 3 ZIKV/3 control Histological processing, including TUNEL assay and immunohistochemistry P1 and P3 Microcephaly, growth restriction, and abnormal vasculature Brain
Vermillion et al., 2017 [33] 4 ZIKV/5 control litters* Histological evaluation of cortical thickness of neonates (Nissl-stained tissue sections), immunohistochemistry, and immunofluorescence imaging P0 Reduction on cortical thickness and reduced litter size Brain
Yockey et al., 2018 [25] Different number of infected and control animals according to period of exposure and described below* Weight, size, gross anomalies, resorption, crown-rump measurement and placental morphology and histology, including immunofluorescence and immunohistochemistry E9.5, E10.5, E11.5 and E12.5 Ifnar1 + / − fetuses present higher growth restriction, death, resorption, lower weight, and placental abnormalities Whole body
Khaiboullina et al., 2019 [34] 26 ZIKV/31 control No morphometric evaluation, just fetal and placental weight GD 17.5 Reduction on fetal and placental weight Whole body
Rathore et al., 2019 [35] At least 5 individuals per each group and for each evaluation Fetal mass, head circumference, cortical thickness, gene expression E8, E10 or E18 Reduction of fetal mass and head circumferences in all groups infected with ZIKV; stunned growth and cortical thickness was also moderately reduced in the fetuses of naïve ZIKV-infected whole embryo, brain, placenta
Westrich et al., 2021 [36] At least 3 individuals per each group Fetal and placental weight and fetal skull area E19 (mice) and E58 (guinea pigs) No differences in fetus and placental weight and in the skull area between ZIKV exposed fetus and mock for mice and guinea pigs Whole fetus, placenta, maternal brain, uterus and spleen
Darbellay et al., 2017 [20] 12 ZIKV/28 control Computed tomography, magnetic resonance imaging, histology, and morphometry 1 PN and 21 PN Neonatal body length and weight in the IP + IA group was lower than in the control group; two piglets had possible neurological or developmental defects Brain
Thawani et al., 2018 [24]

3dpi: 8 ZIKV/10 controls;

7 dpi (brain wet weight): 11 ZIKV/10 controls;

(TE epithelial thickness): 5 ZIKV/5 controls

Magnetic Resonance Imaging to brain size quantification, Histology and Morphometry E5 and E9 ZIKV treated embryos presented MB and FB smaller than controls Whole body

*Pup number not mentioned; dpi: days post infection

E: embryonic day; FB: forebrain; GD: gestational day; MB: midbrain; TE: telencephalon; P and PN: postnatal. Sample number of Yockey et al., 2018: E9.5 uninfected Ifnar1−/− n = 7 and Ifnar1+/− n = 12 from 2 litters infected Ifnar1−/− n = 9 and Ifnar1+/− n = 10 from 3 litters; E10.5 uninfected Ifnar1−/− n = 15 and Ifnar1+/− n = 5 from 3 litters, infected Ifnar1−/− n = 24 and Ifnar1+/− n = 17 from 6 litters; E11.5 uninfected Ifnar1−/− n = 5 and Ifnar1+/− n = 12 from 3 litters, infected Ifnar1−/− n = 12 and Ifnar1+/− n = 11 from 3 litters; E12.5 uninfected Ifnar1−/− n = 11 and Ifnar1+/− n = 11 from 3 litters, infected Ifnar1−/− n = 19 and Ifnar1+/− n = 19 from 5 litters