GPER1 is required to protect fetal health from maternal inflammation

GPER1 in utero to the rescue! Several common pathogens, including influenza A virus (IAV), can activate systemic type I interferon (IFN) signaling during pregnancy. Such infections would be expected to cause birth defects and fetal mortality, but maternal IAV infections rarely produce such effects, suggesting the presence of a protective mechanism in fetal tissues. Harding et al. used a CRISPR screen to uncover IFN regulators that can mediate differential IFN control across tissues in human cell lines. They found that G protein–coupled estrogen receptor 1 (GPER1), which is expressed in fetal tissues, acts as a protective suppressor of IFN responses in the placenta during maternal infection. In a mouse model, pharmacological activation of GPER1 shielded fetuses from maternal inflammation. Activation of GPER1 might be promising therapeutically to protect the fetus from both maternal and fetal infections. Science , this issue p. 271