Research results, Scientific Publications

During pregnancy, the human embryo is initially supplied with nutrients via the yolk sac; later, the placenta takes over this role. It consists of maternal and embryonic tissue, through whose blood vessels the mother’s blood flows. An interdisciplinary research team at Hannover Medical School (MHH) has now demonstrated in a mouse model that, during placental development, tiny, localised blood clots at the interface between maternal and embryonic tissue play an important regulatory role. The physiological significance of these microthrombi for a successful pregnancy is a new finding. Previously, these blood clots were primarily regarded as a cause of pregnancy complications.

“These so-called placental microthrombi play a crucial role: like tiny temporary dams, they restrict the flow of maternal blood at specific points. In this way, they help to direct the blood through the developing placenta,” says Dr. Markus Abeln from the MHH Institute of Clinical Chemistry and Central Laboratory. Together with Dr. Arno Smid, he led this study, which was published in the “Journal of Clinical Investigation”. To carry out the research, the scientists collaborated with several MHH institutes and clinics, including Prof. Dr. Andreas Tiede from the MHH Department of Haematology, Haemostaseology, Oncology and Cell Therapy, as well as Cardiff University. The German Research Foundation (DFG) funded this work as part of the research group “Sialic Acid as Regulator in Development and Immunity”.

Pregnancy requires a delicate balance

The researchers were also able to show that the microthrombi contain maternal platelets as well as proteins that regulate blood clotting (coagulation factors). They also consist of the complement protein C3, a key component of the innate immune system. The scientists investigated how platelets, clotting factors and the complement system interact to form the microthrombi: first, the clotting enzyme thrombin activates the platelets. These then form a surface on which the complement system can be stimulated in a localised manner.
The absence of a specific sugar molecule (sialic acid) on the surface of the placenta led to excessive activation of the complement system, extensive deposits of platelets and clotting factors, excessive thrombosis and severely impaired placental development.

The results show that a successful pregnancy requires a delicate balance: platelets, the coagulation system and the complement system must be sufficiently active to regulate blood flow, but must not trigger an uncontrolled inflammatory or coagulation response. This interplay is essential for preventing bleeding in early pregnancy.

A dysregulation could also be significant in relation to pregnancy complications in humans. Alterations in the complement and coagulation systems have already been described in pre-eclampsia – a serious pregnancy-related condition that can endanger both mother and child – as well as in recurrent miscarriages and adverse pregnancy outcomes associated with autoimmune diseases. However, as the current study was conducted using mouse models, further investigations using human placental tissue and suitable human models are necessary. In the long term, the findings could help to develop more targeted approaches to treat placental thrombosis and excessive complement reactions.

As part of this collaboration, Dr. Abeln joined the Haemostaseology Research Group, led by Dr. Sonja Werwitzke and Professor Tiede. There, he is continuing his research into how blood clotting, the immune system and glycosylation interact.

The placenta

The placenta is a tissue that develops on the wall of the uterus during pregnancy. It forms when embryonic tissue grows into the uterine lining and consists of both embryonic and maternal tissue. The embryo (referred to as the foetus in later stages of development) is connected to the mother’s bloodstream via the placenta. From the twelfth week of pregnancy onwards, the placenta supplies the embryo with nutrients and oxygen. It performs hormonal functions and facilitates the removal of waste products. The placenta influences the mother’s immune system in such a way that it does not reject the child as foreign tissue, whilst at the same time continuing to protect the mother from infections. The connection between the embryo and the placenta is via the umbilical cord. After childbirth, the placenta is expelled as the afterbirth.

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For more information, please contact Dr. Markus Abeln at Abeln.Markus@mh-hannover.de.

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Originalpublikation:
You can find the original publication “Platelets link coagulation and complement in regulating murine placental vascular development” here: https://www.jci.org/articles/view/200372