The organoids will offer a new perspective on the effects of COVID-19 infection on pregnant women and their children. The CoV-2 virus infects the placental barrier between maternal and fetal blood, changing the barrier’s ability to function.
The study sheds light on why unvaccinated pregnant women infected with SARS-CoV-2 are at increased risk of stillbirth or premature infants. It also explains why the risk of getting serious illness from viral infections is more likely in pregnant women. women than in non-pregnant women.
To examine the effects of SARS-CoV-2 on pregnant women and their children, the study team cultured placental organoids. Organoids are created from stem mobiles. Stem mobiles have the remarkable ability to become almost any type of mobile. When those mobiles get the right environmental and chemical signals, they can interact with others and shape human tissue, adding tissues that form structures like the placenta.
The study team created their human skin cells placental organoids. By exposing human skin cells to express chemical signals, the team reprogrammed the skin cells into trophoblastic stem cells. Trophoblastic stem cells can eventually expand into two other types of placental cells: extravillous cytotrophoblasts and syncytiotrophoblasts.
After growing the placental cells and generating the organoid, the researchers tested the lab-grown placental tissue for any receptors historically linked to SARS-CoV-2 infection. Two points for SARS-CoV-2 infection are ACE2 and transmembrane serine protease 2.
ACE2 is a receptor protein that provides an access point for SARS-CoV-2 infection. Transmembrane serine protease 2 activates the SARS-CoV-2 viral spike protein and complements the virus’ ability to enter cells with the ACE2 receptor. By staining placental tissue grown in the lab, the researchers showed that the tissue expressed ACE2 and TMPRSS2. These proteins were specifically expressed in syncytiotrophoblasts.
The team then inflamed their placental tissue with the SARS-CoV-2 virus. Interestingly, while the virus gently inflamed syncytiotrophoblastic cells, trophoblastic stem cells and extravillous cytotrophoblasts remained inflammation-free. These effects were also consistent when the researchers inflamed cells with the Delta and Omicron variants of SARS-CoV-2.
Since syncytiotrophoblasts were the only cells inflamed with SARS-CoV-2, the researchers focused on assessing how the infection altered the function of syncytiotrophoblasts. The syncytiotrophoblast is a layer of the placenta comprising a spectrum of cells ranging from immature stem cells to fully evolved syncytial cells. The placental layer plays a role in the exchange of nutrients and gases between mother and baby.
Figure 2: The researchers focused on the syncytiotrophoblastic (ST) cells that shape a layer of the human placenta.
After analyzing the syncytiotrophoblast cells, the researchers found that the inflamed cells were less mature than the non-inflamed cells. Similarly, they observed that inflamed tissue contained a higher proportion of immature stem cells. These effects suggest that SARS-CoV-2 infection reduces the expansion and progression of syncytiotrophoblastic tissue.
Another measure of the mobile service is the cytotoxic stress point. Cytotoxic stress occurs when external influences cause damage or death to the mobile. To find out if SARS-CoV-2 increases cytotoxic stress, the researchers analyzed their samples for chemicals released by cell phones when injured. Unsurprisingly, the inflamed mobiles emitted particularly high levels of damage-induced signals.
To expand a deeper understanding of the effects of SARS-CoV-2 infection on syncytiotrophoblast cells, the researchers performed genetic testing on the cells. The effects of genetic testing made us think that inflamed cells expressed genes than non-inflamed cells. It should be noted that genes that are expressed in the syncytiotrophoblast were expressed particularly less than in non-inflamed cells. This indicated a loss of service in syncytiotrophoblasts after SARS-CoV-2 infection.
These effects have led to a question; How can researchers save you from SARS-CoV-2 infection in syncytiotrophoblasts?
Since ACE2 serves as an access point for the virus, the researchers investigated whether the ACE2 receptor can be a target to prevent the virus from entering the cell. To do this, they created an anti-ACE2 antibody that could block viral access. .
To check their anti-ACE2 antibody, the researchers exposed the cells to the antibody and the virus, and then assessed whether the cells were inflamed with the virus. To their surprise, the researchers did not stumble upon the infectious virus in cells treated with the anti-ACE2 antibody. In addition, cells treated with the anti-ACE2 antibody had gene expression similar to that of healthy cells and without inflammation. These effects demonstrate that an anti-ACE2 antibody can syncytiotrophoblasts from SARS-CoV-2 infection.
Overall, this study provides valuable insights into how viruses like SARS-CoV-2 not only affect pregnant women, but also their unborn children. While more studies are needed to determine whether anti-ACE2 antibodies can definitively save infections in humans, those findings mark significant progress toward remedies that may be offering greater viral coverage to pregnant women and their children.