Estrogen receptors in the mother’s placenta are critical during viral infection

Durham, North Carolina – Researchers in Duke and Mount Sinai have identified a molecular mechanism that prevents a viral infection during a mother’s pregnancy from harming her unborn child.

When a person becomes infected with a virus, their immune system sends a chemical signal called type 1 interferon, which tells surrounding cells to increase their antiviral defenses, including causing more inflammation.

This response helps prevent the virus from copying itself and gives the adaptive immune system more time to recognize the new invader and begin to hunt it down.

A pregnant woman facing the virus generates these same signals to protect herself, but if the signaling molecules and the resulting inflammation can cross the placenta and reach the fetus, it will lead to serious developmental abnormalities and even fetal death.

But this generally doesn’t happen, with the exception of the Zika virus and a handful of other viruses known to breed inside and harm an embryo. (Although there are nearly 100 million reported cases of COVID-19 to date worldwide, there is no strong evidence that the disease causing virus, SARS-CoV-2, poses a threat to the fetus.)

The research team found a mechanism that protects the fetus from the damage that the mother’s immune response to the virus may cause. In a paper appearing on January 15th Science, They identify the key player in this pathway as an estrogen receptor on the surface of a cell called GPER1, which is specially present in placenta and fetus tissues.

“This likely explains why the fetus does not have many infections during pregnancy,” said study lead Nicholas Heaton, assistant professor of molecular genetics and microbiology at Duke School of Medicine.

After arriving at GPER1 as a potential candidate for this effect through a series of screens, the researchers found that GPER1 receptors are concentrated in the placenta, where the mother’s blood supply passes oxygen and nutrients to the fetus. Estrogen levels are much higher during pregnancy, which makes GPER1 receptors better able to suppress interferon signals in the placenta and fetus development.

Researchers attempted to block this estrogen receptor in pregnant mice with a compound called G15. They found changes to the placenta during influenza A virus infection or G15 treatment, resulting in the pups of young mice. But with both the G15 and the influenza virus, the pups were significantly smaller and many were stillborn.

They also tested the pregnancies of mice infected with Zika virus and influenza B, and observed that the addition of G15 treatment again led to many fetal defects.

“If we disrupt the GPER1 pathway, even a benign maternal infection (such as influenza) will now cause major problems in fetal development,” Heaton said.

Heaton describes it as a pathway because his team has yet to understand how GPER1 provides this protection. They suspect the receiver triggering other downstream mechanisms that play their role.

The beauty of this baby-centered system is that it protects the fetus from infection, Heaton said, while leaving the rest of the mother’s tissues better able to use interferon to fight the virus.

The researchers will then run tests on whether “hyper-activation” of the GPER1 pathway would be a way to protect the growth of the fetus when the mother is infected with the virus.


This research was supported by the National Institutes of Health, the National Institute of Allergy and Infectious Diseases, the National Heart, Lung, and Blood Institute, and the Hartwell Foundation. (Grant number T32-CA009111, T32-AI07647, R21AI139593, R21AI144844, R01AI37031, R01HL142985)

Quote: “GPER1 is required to protect fetal health from maternal infection,” Alfred Harding, Marisa Goff, Heather Froggatt, Jane Lim, Nicholas Heaton. Science، 15 January 2021. DOI: 10.1126 / science.aba9001

https: //Today.duke.Edo /2021 /01 /Estrogen receptor-mum% E2% 80% 99s-placenta is critical during viral infection

Related Articles

Leave a Reply

Your email address will not be published. Required fields are marked *

Back to top button