A small gland, the thymus, hidden behind the sternum, helps prevent miscarriages and diabetes in pregnant women.
- The thymus has been identified as playing an important role in both metabolic control and immunity during pregnancy.
- The thymus is stimulated by female sex hormones that command dramatic changes at the time of pregnancy to produce specialized cells called Tregs.
- The results offered new molecular insights into the development of diabetes during pregnancy which affects approximately 15% of pregnant women.
How the immune system adapts to support mother and fetus is complex. An international research team led by the University of British Columbia (UBC) has uncovered one of these mysteries. She discovered for the first time the importance of a small gland hidden behind the sternum that works to prevent miscarriages and diabetes in pregnant women. They presented their discovery on December 23 in the journal Nature.
A key molecule
The organ in question is the thymus, identified as playing an important role in both metabolic control and immunity during pregnancy. The thymus is stimulated by female sex hormones that command dramatic changes at the time of pregnancy to produce specialized cells called Tregs. These make it possible to cope with the physiological changes that occur during pregnancy.
The researchers also identified “Rank,” a receptor expressed in a part of the thymus called the epithelium, as the key molecule behind this mechanism. “We knew Rank was expressed in the thymus, but its role in pregnancy was unknown,” replaces the study’s lead author, Dr. Josef Penninger, a professor in the department of medical genetics and director of UBC’s Life Sciences Institute. To better understand the role of this molecule, the authors studied mice in which Rank had been deleted from the thymus. “Absence of Rank prevented Treg production in the thymus during pregnancyobserved Dr. Magdalena Paolino, author of the study. This led to a decrease in the number of Tregs in the placentas, resulting in high rates of miscarriages.”
A better understanding of gestational diabetes
The results offered new molecular insights into the development of diabetes during pregnancy which affects approximately 15% of pregnant women. During pregnancy, researchers have found that Tregs migrate to the mother’s fatty tissue to prevent inflammation and help control glucose levels in the body. Pregnant mice that lack the Rank receptor have elevated levels of glucose and insulin in their blood and many other indicators of gestational diabetes. “Just like the babies of women with diabetes during pregnancy, the newborns were much heavier than average”, adds Dr. Magdalena Paolino.
Treg deficiency during pregnancy also had lasting effects on the newborn. The baby mice remained prone to diabetes and overweight throughout their lives. Giving the Rank-deficient mice thymus-derived Tregs reversed all of their health issues, including miscarriages and maternal glucose levels, and also normalized the body weight of their offspring. The researchers also analyzed women with diabetes during pregnancy, revealing reduced numbers of Tregs in their placentas, similar to the mouse study. “The discovery of this new mechanism underlying gestational diabetes potentially offers new therapeutic targets for the mother and the fetus in the future.”, rejoiced the co-author Dr. Alexandra Kautzky-Willer.
“The thymus changes massively during pregnancy and how such rewiring of an entire tissue contributes to a healthy pregnancy has been one of the remaining mysteries of immunology.concludes Dr. Penninger. Our work over many years has not only solved this puzzle – pregnancy hormones rewire the thymus via RANK – but has uncovered a new paradigm for its function: the thymus not only changes the mother’s immune system so that it does not reject the fetus but the thymus also controls the metabolic health of the mother. This research changes our view of the thymus as an active and dynamic organ necessary to protect pregnancies.”
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