About this Research Topic
Human haemochorial placentation is unique since there is a very deep trophoblast invasion into maternal uterine tissues and an intimate contact between maternal and fetal cells at the maternal-fetal interfaces. Therefore, the establishment and maintenance of human pregnancy requires tightly controlled immune interactions and tolerance mechanisms, which include cellular, microvesicular and molecular transport of biological information and signaling between the mother and the fetus. The related immune interactions and trophoblast invasion mechanisms can be severely impacted by the malfunctioning of the placenta, the systemic inflammation or infection of the mother, local infections of the uterine cavity, as well as some other causes. The failure of these mechanisms has been observed in a spectrum of pregnancy complications.
Humans have an extraordinarily high rate of implantation failure, miscarriages and obstetrical syndromes (e.g. preeclampsia, intrauterine growth restriction) compared to other species. For example, 15% of clinically recognized pregnancies end with miscarriage and ~25% of the remainder are affected by these syndromes. Pregnancies impacted by these syndromes have complex pathology, since mothers and fetuses can be both severely affected. Moreover, women who develop these syndromes are also at high risk for metabolic and cardiovascular diseases later in life. Furthermore, in 5-18% of cases babies are born preterm with the sequelae of prematurity, low birth-weight and severe neuro-developmental disorders including cerebral palsy. Barker’s theory and further observations demonstrated that babies born from pregnancies affected by these syndromes also have high risk for diabetes, metabolic syndrome or cardiovascular disease later in life due to the developmental origins of these adult diseases. Due to the enormous hospitalization and rehabilitation care costs as well as long-term sequelae, these obstetrical syndromes are of major medical concern and are a significant healthcare burden throughout the world.
The clinical symptoms, phenotypes and outcomes in patients affected by pregnancy complications can be quite different in spite of the overlapping placental pathologies, which hinder advances in early diagnostic and personalized therapeutic strategies. The extent of the problem with immune or trophoblast malfunctioning and the symptoms of patients vary between patients due to a complex interplay between maternal and fetal, (epi)genetic, immunological, hormonal, metabolic make-up, nutrition and environmental factors affecting final pregnancy outcome. The exact mechanisms of these pregnancy complications can only be understood at the level of signaling pathways or gene regulatory networks, an area of research that has recently been rising in perinatal medicine.
This Research Topic aims to summarize recent developments in the field, focusing on:
(i) How fetal cells (e.g. trophoblast) and molecules released from the placenta may re-set and regulate maternal immune system during pregnancy;
(ii) How maternal immune cells modulate placental functions;
(iii) How maternal infections and local or systemic inflammation may affect placental and fetal development and health later in life and
(iv) How systems biological approaches can stratify patients based on disease pathways and define new diagnostic and personalized therapeutic tools.
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