Tiny blood clots help guide blood flow as placenta develops, mouse study finds
· Medical Xpressby Inka Burow, Hannover Medical School
edited by Lisa Lock, reviewed by Andrew Zinin
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During pregnancy, the human embryo is initially supplied with nutrients through 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 demonstrated in a mouse model that tiny, localized blood clots at the interface between maternal and embryonic tissue play an important regulatory role during placental development.
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, who led the study with Dr. Arno Smid. Their research was published in the Journal of Clinical Investigation.
The scientists collaborated with several MHH institutes and clinics, including Dr. Andreas Tiede from the MHH Department of Hematology, Hemostaseology, Oncology and Cell Therapy, as well as Cardiff University.
Pregnancy requires a delicate balance
The researchers also showed that the microthrombi contain maternal platelets and proteins that regulate blood clotting (coagulation factors). They also contain 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 locally.
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.
Dysregulation could also be significant in pregnancy complications in humans. Alterations in the complement and coagulation systems have already been described in preeclampsia—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, because the current study used mouse models, further investigations using human placental tissue and suitable human models are necessary. In the long term, the findings could help develop more targeted approaches to treat placental thrombosis and excessive complement reactions.
As part of this collaboration, Abeln joined the Hemostaseology Research Group, led by Dr. Sonja Werwitzke and 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 fetus in later stages of development) is connected to the mother's bloodstream through the placenta.
From the 12th week of pregnancy onward, 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 so that it does not reject the child as foreign tissue while continuing to protect the mother from infections. The embryo is connected to the placenta by the umbilical cord. After childbirth, the placenta is expelled as the afterbirth.
Publication details
Arno Smid et al, Platelets link coagulation and complement in regulating murine placental vascular development, Journal of Clinical Investigation (2026). DOI: 10.1172/jci200372
Journal information: Journal of Clinical Investigation
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Obstetrics & gynecologyPregnancy Provided by Hannover Medical School Who's behind this story?
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