Abstract schematic of syncytiotrophoblast stress in maternal COVID-19 and preeclampsia. Credit score: American Journal of Obstetrics and Gynecology (2025). DOI: 10.1016/j.ajog.2025.01.028
A research printed within the American Journal of Obstetrics & Gynecology by researchers at Baylor Faculty of Medication, UTHealth Houston and collaborating establishments reveals that maternal COVID-19 an infection triggers distinct stress responses within the placenta, together with upregulation of preeclampsia-associated genes.
The stress responses promote cell proliferation within the placenta that reinforces the barrier between the fetus and maternal blood circulation. Evaluating placental stress responses in COVID-19 and preeclampsia revealed similarities which will assist clarify the overlapping presentation of those medical syndromes.
“It’s well known that maternal COVID-19 increases the risk of adverse pregnancy outcomes, including preeclampsia, stillbirth and preterm delivery,” mentioned first creator Rachel Keuls, graduate scholar in Dr. Ronald Parchem lab at Baylor. Parchem, co-corresponding creator of the work, is an affiliate professor of molecular and mobile biology and member of the Stem Cells and Regenerative Medication Middle and Dan L Duncan Complete Most cancers Middle at Baylor.
The virus triggers a cytokine storm within the mom—an extreme, uncontrolled launch of mediators of sturdy inflammatory immune responses. The cytokines circulating within the maternal blood attain the syncytiotrophoblasts, specialised epithelial cells that type the outermost layer of the placenta, a barrier that separates maternal and fetal circulation and whose capabilities embody defending the fetus from disease-causing microbes and poisonous compounds. Syncytiotrophoblasts reply to the maternal cytokine storm with a stress response of their very own that isn’t effectively understood.
“In the current study, we investigated the syncytiotrophoblast stress response within the human placenta from mothers with COVID-19 at birth,” Keuls mentioned. “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.”
Syncytiotrophoblasts are distinctive as a result of they’re fused, multinucleated cells as a substitute of typical cells with one nucleus, posing a problem to profiling gene expression in syncytiotrophoblasts with excessive decision utilizing present strategies. To know how syncytiotrophoblasts responded to maternal COVID-19, the researchers used single-nucleus transcriptional profiling, a method to establish modifications in gene expression that circumvents the challenges related to capturing syncytiotrophoblasts with strategies beforehand used for profiling the placenta.
“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,” mentioned co-corresponding creator Dr. Jacqueline G. Parchem, assistant professor within the Division of Obstetrics, Gynecology and Reproductive Sciences at McGovern Medical Faculty at UTHealth Houston. She is also an adjunct school member within the Division of Molecular and Mobile Biology at Baylor.
The precise place, on the proper time
“This project has been very close to the team personally,” Parchem mentioned. “I used to be pregnant throughout the early days of the pandemic and anxious in regards to the unknown penalties getting contaminated would have on the newborn. I used to be extraordinarily invested in understanding the biology. We didn’t know then whether or not the virus contaminated the placenta straight, and a vaccine was not obtainable, but.
“But we were in a unique position to find answers about how this newly emerging and rapidly spreading virus affected pregnancies. As a physician, I was able to collect placenta samples for our study. It would be impossible to collect severe, primary infection cases from unvaccinated patients today.”
“I conducted the analyses of the placentas working through the very early days of the pandemic,” Keuls mentioned. “As a developmental biologist, I applied my expertise to study the placentas at high cellular resolution to explore uncharted territory, something we knew nothing about—what the direct effects of COVID-19 were on the placenta. I worked in the deserted lab, walked empty hallways. Most of the lights were off in the buildings as access was limited due to the pandemic. These were difficult times, but the findings are very rewarding.”
Extra info:
Rachel A. Keuls et al, Single-nucleus transcriptional profiling of the placenta reveals the syncytiotrophoblast stress response to COVID-19, American Journal of Obstetrics and Gynecology (2025). DOI: 10.1016/j.ajog.2025.01.028
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Human placenta stress response to maternal COVID-19 an infection reinforces maternal-fetal barrier (2025, April 22)
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