A new article published in Nature demonstrates miscarriages during pregnancy could have a surprising link to a very small gland called the thymus.
Efficient pregnancies depend on the mother's adaptations, including major immune system changes. The thymus, the central lymphoid gland, has long been known to change dramatically during pregnancy. In the study, researchers showed that the "RANK" osteoclast differentiation receptor links female sex hormones with thymus rewiring during birth. The authors say RANK facilitates the hormone mediated growth and improved functional role of maternal T cells during breastfeeding.
The thymus is a specialized primary lymphoid organ of the immune system. T cells are critical to the adaptive immune system, where the body adapts specifically to foreign invaders. Abnormalities of the thymus can result in autoimmune diseases such as Autoimmune polyendocrine syndrome type 1 and myasthenia gravis. These are often associated with cancer of the tissue of the Thymus.
"We knew RANK was expressed in the thymus, but its role in pregnancy was unknown, says the study's senior author Dr. Penninger, professor in the department of medical genetics and director of the Life Sciences Institute at UBC according to Science Daily.
Biologists have long wondered how the immune system adapts to protect the mother and fetus. The analysis led by an international team of scholars, including Dr. Josef Penninger of UBC reveals a potential answer. The researchers also showed that female sex hormones are instructing the development of specialized T cells to cope with the physiological changes that occur during pregnancy in significant changes in the thymus.
The researchers used mice, where RANK was excluded from the thymus to achieve a deeper understanding. The formation of thymic T cells by RANK, in a way that relies on thymic medullary epithelial cells, drives sex hormones, in particular progesterone. The RANK decline in the mice led to a reduction of natural T cell accumulation in the placenta as well as an increase in miscarriages.
Pregnant mice without RANK had elevated blood glucose levels and insulin, as well as many other gestational diabetes markers, including larger-than-average offspring. T cell dysfunction during birth has also had long-term gender-based effects on the infants. The offspring of the lab mice remained vulnerable to diabetes and overweight throughout their life.
"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" according to Penninger. The author suggests the research also "uncovered a new paradigm for its function: the thymus not only changes the immune system of the mother so it does not reject the fetus, but the thymus also controls metabolic health of the mother."