July 19, 2024

Yale Researchers Discover the Crucial Role of Protein CXCR4 in Pregnancy

Researchers from Yale have made a significant discovery regarding the role of immune cells during pregnancy. In a study published in the journal JCI Insight, the team found that a protein called CXCR4, which is present throughout the body, plays a major role in modulating the immune system during pregnancy. This modulation is essential for the development of the fetus and the protection of both the parent and fetus from external threats such as viruses. The findings of the study could potentially pave the way for new treatments for reproductive conditions in the future.

During pregnancy, the immune system needs to adjust its responses to strike a balance between tolerating the developing fetus and defending against potentially harmful foreign organisms. Many of these adaptations occur within the decidua, the tissue that surrounds and interacts with the placenta. Previous studies conducted by the same research team revealed that bone marrow cells, including immune cells, migrate to the uterus and the decidua early in pregnancy. The researchers were particularly interested in understanding the mechanisms that attract these cells to the pregnant uterus.

Previous research has indicated that a protein called C-X-C chemokine receptor type 4 (CXCR4), as well as its binding protein, are crucial for the trafficking of bone marrow cells in various organs and tissues throughout the body. CXCR4 is also found in higher concentrations in the uterus at the start of pregnancy. To investigate the role of CXCR4 in pregnancy, the researchers deleted the gene responsible for coding this protein in adult female mice. This removal effectively eliminated the protein from the body.

The results showed that the mice lacking CXCR4 experienced a greater number of fetal losses during pregnancy and had smaller litter sizes compared to normal mice. However, when the researchers specifically removed CXCR4 only in the uterus, there were no negative effects on pregnancy. This finding suggested that it is not the expression of CXCR4 within uterine cells themselves that is crucial, but rather the expression of CXCR4 from outside the uterus that plays a significant role in maintaining pregnancy, according to Dr. Reshef Tal, the lead researcher of the study.

As immune cells are recruited to the uterus from outside the organ, the researchers then examined how the deletion of CXCR4 affected immune cell populations in the decidua. They discovered that in mice without CXCR4, fewer natural killer cells were trafficked to the uterus, and those that did arrive clustered abnormally. Additionally, these natural killer cells expressed lower levels of a particular enzyme called granzyme B, leading to an abnormal inflammatory response in the uterus. The mice also exhibited irregular blood vessel arrangement in the placenta and decidua, potentially impacting the exchange of nutrients between the parent and fetus.

To confirm whether these changes were caused by immune cell dysfunction, the researchers transplanted healthy bone marrow from normal mice into mice lacking CXCR4. The results showed that this transplantation significantly rescued the effects observed. The mice with transplanted bone marrow experienced fewer pregnancy losses and had normal levels of natural killer cells, proper cell distribution, enzyme expression, and blood vessel arrangement in the placenta.

Dr. Tal highlighted that one of the main findings of the study is the potential to utilize the ability of bone marrow cells to target the uterus and influence both the immune status of the decidua and the vascular remodeling of the placenta. This knowledge could lead to the development of new cell therapy approaches for reproductive conditions such as recurrent pregnancy loss and preeclampsia. According to Dr. Tal, these conditions are believed to involve an imbalance in immune factors and factors related to blood vessel formation. The findings of this study could potentially pave the way for innovative treatments for these conditions in the future.

1. Source: Coherent Market Insights, Public sources, Desk research
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