BREAKING NEWS! COVID-19 Infections During Pregnancy Alters Expression Of Important Pregnancy Genes That Can Give Rise To Complications!
SARS-CoV-2 Infection Induced Substantial Changes To The Epigenome And Transcriptome At The Maternal–Fetal Interface, Which Can Cause Pregnancy Complications!
: In a new study conducted by researchers at The Hong Kong University of Science and Technology-China, the intricate molecular changes that occur in the maternal-fetal interface during COVID-19 infections have been unveiled. These changes, affecting both the epigenome and transcriptome, have been found to potentially contribute to pregnancy complications.
Pregnancy is a delicate phase in a woman's life, and any disruption at the maternal-fetal interface can lead to adverse outcomes.
Previous studies have shown an increased incidence of complications in pregnant patients with COVID-19, but the underlying mechanisms have remained elusive.
This new research aimed to explore the molecular impacts of SARS-CoV-2 infection on the maternal-fetal interface, shedding light on the intricate interactions that take place during pregnancy.
By analyzing bulk and single-nucleus transcriptomic and epigenomic profiles from patients with COVID-19 and control samples, the study team discovered significant immune activation and angiogenesis dysregulation in distinct cells from infected individuals. Surprisingly, they also observed dysregulation of retrotransposons in specific cell types. Retrotransposons, which are derived from retroviruses, play a crucial role in normal placental development and function. However, viral infections, including SARS-CoV-2, have been associated with the abnormal activation of retrotransposons, potentially leading to widespread transcriptional dysregulation.
The precise molecular mechanism behind COVID-19-associated pregnancy complications has been a subject of uncertainty. To unravel the complexities of the maternal-fetal interface, the study team conducted cell type-specific analyses.
Corresponding author, Dr Danny Leung from the Center for Epigenomics Research at the Hong Kong University of Science and Technology told Thailand Medical
News, “While previous studies had focused on single-nucleus transcriptomics, this study also explored the associated epigenomic alterations. The results revealed global changes in gene expression and epigenetic marks in patients, including the misregulation of immune-response and angiogenesis genes.”
Interestingly, the study team identified dysregulated retrotransposons, specifically enhancers derived from a retrotransposon called LTR8B. These enhancers were found to be functionally linked to the downregulation of pregnancy-specific glycoprotein genes in syncytiotrophoblasts, a type of placental cell. Pregnancy-specific glycoproteins play crucial roles in immunoregulation, angiogenesis, and preventing blood clotting during pregnancy. Their disruption is associated with complications such as preeclampsia.
The study also revealed that reduced enhancer activities at LTR8B-derived elements, along with th
e downregulation of the transcription factor GATA2, contributed to decreased expression of pregnancy-specific glycoproteins in patients with COVID-19.
Throughout the COVID-19 pandemic, hospitals have seen an increasing number of pregnant patients infected with SARS-CoV-2. While it has been established that these patients face higher risks of adverse pregnancy outcomes, this research provides valuable insights into the molecular mechanisms underlying these complications.
The findings indicate that patients with COVID-19 may have a higher susceptibility to placenta-related complications, necessitating specific care and management strategies.
The study also highlighted the importance of immunomodulation at the maternal-fetal interface for successful pregnancies. Aberrant interferon expression, a common cause of pregnancy disorders, was observed across different cell types in patients with COVID-19. Furthermore, abnormal angiogenesis, a known feature of various pregnancy complications, was found to be dysregulated in patients, potentially contributing to endothelial dysfunction.
The dysregulation of retrotransposons, revealed by this study, adds another layer of complexity to our understanding of the impact of COVID-19 on pregnancy.
Retrotransposons have extensive regulatory roles in normal placental function, and their dysregulation may disrupt important molecular processes, leading to pregnancy complications.
In conclusion, this comprehensive research has provided extensive multi-omic datasets that uncover the critical role of epigenetic regulation and retrotransposon-derived enhancers in COVID-19-related pregnancy complications.
The findings emphasize the need for further studies to investigate whether new variants of SARS-CoV-2 could induce similar immune activation and angiogenesis dysregulation.
The study findings were published in the peer reviewed journal: Nature Cell Biology.
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