Journal of global health · 2025
COVID-19 vaccination and miscarriage risk: RNA-seq and bioinformatics analysis at the maternal-foetal interface.
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Qu Yiyuan, Zhu Chengcheng, Sun Tao, Jiang Jianqiu, Gu Ying, Jin Linping, Huang Xujia, Wu Bingbing, Xu Jian, Chen Xiuying
Аннотация
BACKGROUND: Vaccine hesitancy persists because definitive evidence regarding the underexplored safety of COVID-19 vaccines in pregnancy is still lacking, particularly concerning their effects on the maternal-foetal interface (MFI) and potential links to miscarriage. We aimed to verify whether COVID-19 vaccines modulate gene expression at the MFI, thereby influencing recurrent miscarriage.
METHODS: We conducted an RNA sequencing analysis on decidual tissues from six pairs of early pregnancy participants, both vaccinated and unvaccinated. We extracted the data sets associated with COVID-19 placenta (GSE181238) and recurrent miscarriage (GSE22490) from the Gene Expression Omnibus database for further bioinformatic analysis, focussing on the expression, function, and distribution of core genes at the MFI.
RESULTS: Compared to the control group, 879 differentially expressed genes (P < 0.05; fold changes >1.5; false discovery rate <0.05) were identified in the vaccinated group. Complement activation and cell adhesion pathways were up-regulated, while the graft-vs-host response was down-regulated. The vaccine down-regulated some genes overexpressed in recurrent miscarriage cases. Three significant genes - FOS, FOSB, and LY96 - associated with miscarriage were identified; these genes are up-regulated during infection but suppressed by the vaccine. Functional enrichment analysis revealed the vaccine's immune activity, similar to but weaker than COVID-19 infection, and it inhibited certain miscarriage-related pathways, such as the tumour necrosis factor signalling pathway. Gene set variation analysis suggested a positive influence of the vaccine on immune tolerance at MFI.
CONCLUSIONS: This study indicates that the COVID-19 vaccine may exert nonnegative effects on the maternal-foetal immune micro-environment and is unlikely to increase the risk of miscarriage.
METHODS: We conducted an RNA sequencing analysis on decidual tissues from six pairs of early pregnancy participants, both vaccinated and unvaccinated. We extracted the data sets associated with COVID-19 placenta (GSE181238) and recurrent miscarriage (GSE22490) from the Gene Expression Omnibus database for further bioinformatic analysis, focussing on the expression, function, and distribution of core genes at the MFI.
RESULTS: Compared to the control group, 879 differentially expressed genes (P < 0.05; fold changes >1.5; false discovery rate <0.05) were identified in the vaccinated group. Complement activation and cell adhesion pathways were up-regulated, while the graft-vs-host response was down-regulated. The vaccine down-regulated some genes overexpressed in recurrent miscarriage cases. Three significant genes - FOS, FOSB, and LY96 - associated with miscarriage were identified; these genes are up-regulated during infection but suppressed by the vaccine. Functional enrichment analysis revealed the vaccine's immune activity, similar to but weaker than COVID-19 infection, and it inhibited certain miscarriage-related pathways, such as the tumour necrosis factor signalling pathway. Gene set variation analysis suggested a positive influence of the vaccine on immune tolerance at MFI.
CONCLUSIONS: This study indicates that the COVID-19 vaccine may exert nonnegative effects on the maternal-foetal immune micro-environment and is unlikely to increase the risk of miscarriage.