Thymus gland works to prevent miscarriage, diabetes in pregnant women

An international research team led by the University of British Columbia (UBC) has discovered for the first time the importance of a small gland behind the sternum that works to prevent miscarriage and miscarriage. diabetes in pregnant women.

The thymus is the organ, which was identified in a study published today in the journal Nature as playing an important role in metabolic control and immunity in pregnancy.

How the immune system is changing to support both mother and fetus has been a concern for researchers for decades. The study – conducted by an international research team, comprising Drs. Josef Penninger at UBC – reveals response. The researchers have found that female sex hormones direct important changes in the thymus, a key organ of the immune system, to produce specific cells called Tregs to counteract the resulting physiological changes. the crop in pregnancy.

The researchers also identified RANK, a receptor expressed in a part of the thymus called the epithelium, as the main molecules behind this mechanism.

We knew that RANK was expressed in the thymus, but its role in pregnancy was unknown.. “

Dr. Josef Penninger, Senior Research Author and Professor, Department of Medical Genetics and Director of the Institute of Life Sciences, University of British Columbia

To gain a better understanding, the authors studied mice where RANK was excised from the thymus.

“The absence of RANK prevented Tregs from being excreted in the thymus during pregnancy. As a result there were fewer Tregs in the placentas, leading to high levels of miscarriage,” said the lead author of the study, Dr. Magdalena Paolino, assistant professor in the field of medicine. at the Karolinska Institute.

The findings also offer new molecular perspectives on the development of diabetes during pregnancy, known as gestational diabetes, a disease that affects about 15 percent of pregnant women across the world. the world, and about which scientists still do not know much.

In a healthy pregnancy, the researchers found that Tregs moved to maternal fat tightening to prevent inflammation and help control glucose levels in the body. Pregnant mice lacking RANK and many other signs of gestational diabetes had high levels of glucose and insulin, including higher-than-average juveniles.

“Like the babies of pregnant women with diabetes, the newborn pups were much heavier than average,” says Dr. Paolino.

The lack of Tregs during pregnancy also led to long-term intergenerational effects on the children. Puppies were still susceptible to diabetes and obesity throughout their lives. Providing the mice derived from thymus with RANK mice separated from pregnancy by a normal child eliminated their health issues, including premature birth and maternal glucose levels, and also normalize the body weights of the pups.

The researchers also analyzed women with diabetes during pregnancy, showing a smaller number of Tregs in their placentas, similar to the study in mice.

“This new approach that underlies gestational diabetes may find new therapeutic targets for future mothers and fetuses,” said co-author Dr. Alexandra Kautzky-Willer, clinical researcher based at the University of Medicine Vienna.

“The thymus changes dramatically during pregnancy and how a full-fledged relapse contributes to a healthy pregnancy has become one of the remaining mysteries of immunology,” says Dr. Penninger. “Our work over a number of years has now solved this puzzle – fetal hormones regenerate the thymus through RANK – but they have found a new paradigm for its function: the thymus is not -only alters the mother’s immune system so that it does not reject the fetus, but the thymus also controls the mother’s metabolic health.

“This research is changing our view of the thymus as an active and dynamic organ needed to prevent pregnancy,” says Dr. Penninger.