A recent study has been published in the American Journal of Obstetrics & Gynecology by researchers from Baylor College of Medicine and UTHealth Houston, among other institutions. The findings indicate that maternal COVID-19 infection triggers specific stress responses in the placenta. These responses involve the upregulation of preeclampsia-associated genes and promote cell proliferation, reinforcing the barrier between the fetus and maternal blood.
“It's well known that maternal COVID-19 increases the risk of adverse pregnancy outcomes, including preeclampsia, stillbirth and preterm delivery,” explained Rachel Keuls, first author and graduate student in Dr. Ronald Parchem's lab at Baylor. Parchem, who is a co-corresponding author, holds a position as associate professor of molecular and cellular biology at Baylor and is also affiliated with the Stem Cells and Regenerative Medicine Center and the Dan L Duncan Comprehensive Cancer Center.
The study highlights that the virus can initiate a cytokine storm in the mother, leading to an excessive immune response. These cytokines can reach the syncytiotrophoblasts, specialized cells forming the placenta's outer layer. While the understanding of these cells' stress responses to the maternal inflammatory reaction is limited, the current study explored the syncytiotrophoblast stress response specifically in placentas from mothers with COVID-19.
Keuls noted, “It’s important to note that direct placental infection with the COVID-19 virus is rare. The placental stress responses are triggered by the maternal inflammatory response to the virus.”
To examine gene expression changes despite challenges associated with profiling these unique multinucleated cells, researchers employed single-nucleus transcriptional profiling. This method enabled the identification of multiple syncytiotrophoblast clusters, each with distinct gene expression responses to maternal inflammation.
“This technique revealed multiple clusters of syncytiotrophoblasts. Each cluster expresses a different set of genes, meaning that the clusters have distinct stress responses to the COVID-19-triggered maternal inflammatory response,” said Dr. Jacqueline G. Parchem, co-corresponding author and assistant professor at UTHealth Houston.
The project was particularly significant for Dr. Parchem on a personal level. She recounted, “I was pregnant during the early days of the pandemic and concerned about the unknown consequences getting infected would have on the baby. I was extremely invested in understanding the biology.”
Keuls reflected on the project's unique challenges, stating, “I conducted the analyses of the placentas working through the very early days of the pandemic,” adding that these efforts during difficult times led to rewarding findings.
The researchers received support from various sources, including the Center for Clinical and Translational Sciences COVID-19 Pilot Grant and the Department of Obstetrics and Gynecology at UTHealth Houston, along with other notable grants. Contributions to the study came from Scott A. Ochsner, Mary B. O’Neill, Diana R. O’Day, Akihiko Miyauchi, Kadeshia M. Campbell, Natalie Lanners, Jeffrey A. Goldstein, Connor Yee, Neil J. McKenna, and Ronald J. Parchem.
