tetano
Editor, Senior Moderator
J Glob Health
. 2025 Nov 14:15:04129.
doi: 10.7189/jogh.15.04129. COVID-19 vaccination and miscarriage risk: RNA-seq and bioinformatics analysis at the maternal-foetal interface
Yiyuan Qu[SUP] #[/SUP][SUP] 1 [/SUP], Chengcheng Zhu[SUP] #[/SUP][SUP] 1 [/SUP], Tao Sun[SUP] 1 [/SUP], Jianqiu Jiang[SUP] 1 [/SUP], Ying Gu[SUP] 1 [/SUP], Linping Jin[SUP] 1 [/SUP], Xujia Huang[SUP] 1 [/SUP], Bingbing Wu[SUP] 1 [/SUP], Jian Xu[SUP] 1 2 [/SUP], Xiuying Chen[SUP] 1 [/SUP]
Affiliations
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.
. 2025 Nov 14:15:04129.
doi: 10.7189/jogh.15.04129. COVID-19 vaccination and miscarriage risk: RNA-seq and bioinformatics analysis at the maternal-foetal interface
Yiyuan Qu[SUP] #[/SUP][SUP] 1 [/SUP], Chengcheng Zhu[SUP] #[/SUP][SUP] 1 [/SUP], Tao Sun[SUP] 1 [/SUP], Jianqiu Jiang[SUP] 1 [/SUP], Ying Gu[SUP] 1 [/SUP], Linping Jin[SUP] 1 [/SUP], Xujia Huang[SUP] 1 [/SUP], Bingbing Wu[SUP] 1 [/SUP], Jian Xu[SUP] 1 2 [/SUP], Xiuying Chen[SUP] 1 [/SUP]
Affiliations
- PMID: 41232126
- DOI: 10.7189/jogh.15.04129
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.