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Study results published in 05/15/18 issue of Immunity reveal how natural killer cells produce proteins in the uterus and retain memory for healthier future pregnancies
June 6, 2018 – NEW YORK, NY – Researchers at Hadassah Medical Organization in Israel have identified “natural killer cells” as a key component in answering the perplexing question as to why each subsequent pregnancy is easier and healthier than the first, according to Ellen Hershkin, President, Hadassah, The Women’s Zionist Organization in America, Inc. (HWZOA). The study results, published in the May 15th issue of the medical journal immunity, are the product of six years of research led by Dr. Simcha Yagel, head of OB/GYN at HMO, and included analyzing tissue samples from more than 450 pregnancies.
Hershkin states, “Once again, HMO researchers are in the vanguard of providing life-saving, state-of-the-art medical research that is critical to the care, safety and wellbeing of women not only in Israel but around the world. This new study furthers Hadassah’s mission to protect and empower women at one of the most critical and defining moments of their life.”
Natural killer cells are part of the body’s immune system and their name is derived from their ability to wipe out tumors and pathogen-infected cells. These same cells are abundant in the human decidua, the lining of the uterus that forms the maternal part of the placenta during pregnancy.
Yagel’s research, a type of biology called epigenetics, studies the change in an organism caused by modifications of gene expression. Yagel and his team discovered a population of natural killer cells found in repeated pregnancies which has a unique transcription and epigenetic signature and named them “Pregnancy Trained Decidual Natural Killer Cells (PTdNK).”
Natural killer cells help protect the embryo and ensure its development, although they can also cause problems. Yagel explains: “A fetus is essentially a parasite or a tumor. It invades the mother’s tissue and now receives oxygen and nutrient from the mother. 70% of cells in the fetal-maternal interface are natural killer cells. That’s too much for just immune protection so we delved further and discovered that rather than ‘kill,’ the natural killer cells actually improve the chances of a healthy child by producing proteins that support the pregnancy. We should actually call them ‘natural builder cells.’ The biggest surprise was that these natural killer cells have memory – they fight diseases such as the CMV virus. These cells also improve ‘placentation,’ the formation or arrangement of the placenta.”
Yagel and his research team note that this is why preclampsia, a condition caused by inadequate placentation, drops in subsequent pregnancies. Yagel opines: “Our findings may provide an explanation as to why complications of pregnancy, especially the ‘great obstetrical syndromes’ (intrauterine growth and small birth size) are less frequent in repeated pregnancies.”
Yagel’s goal is to develop a test to screen risk factors. “By understanding how natural killer cells work, we can ask what’s missing in the first pregnancies and eventually develop a treatment,” Yagel notes.
One possibility the researchers suggest: an artificial expansion or manipulation of natural killer cells during the women’s menstrual cycle prior to pregnancy. That’s possible because natural killer cells with their unique “memory” function accumulate in menstrual blood. According to Yagel, “The cells seem to be waiting for the next pregnancy.”
Other team members in the project came from across departments at Hadassah Hebrew University, including the Foundation Laboratories at the Lautenberg Centre for Immunology and Cancer Research, the Magda and Richard Hoffman Center for Human Placenta Research, the Department of Obstetrics and Gynecology, and the Department of Developmental Biology and Cancer Research. Additional research support was provided by the Department of Molecular Genetics and the Department of Immunology at the Weizmann Institute of Science in Rehovot.
Hadassah, the Women’s Zionist Organization of America, Inc. (HWZOA) is the largest Jewish women’s organization in the United States. With 330,000 members, associates and supporters Hadassah brings Jewish women together to effect change and advocate on critical issues such as medical care and research and women's empowerment. Through the Hadassah Medical Organization's two hospitals, the world-renowned trauma center and the leading research facility in Jerusalem, Hadassah supports the delivery of exemplary patient care to over a million people every year. HMO serves without regard to race, religion or nationality and earned a Nobel Peace Prize Nomination in 2005 for building “bridges to peace” through equality in medical treatment. For more information, visit www.hadassah.org.