Placenta defects critical factor in prenatal deaths

The role of the placenta in healthy foetal development is being seriously under-appreciated according to a new paper The study was part of the Wellcome-funded “Deciphering the Mechanisms of Developmental Disorders (DMDD)” consortium. Dr Myriam Hemberger at the Babraham Institute, Cambridge led the research, working with colleagues at the Wellcome Sanger Institute, Cambridge, the Francis Crick Institute, London, the University of Oxford and the Medical University of Vienna, Austria. The team studied 103 genetic mutations in mice that cause embryos to die before birth. The results showed that the majority, almost 70 per cent, cause defects in the placenta.
Each of the 103 gene mutations causes the loss of a particular factor. Many of these had not been previously linked to placenta development, and hence the study highlights the unexpected number of genes that affect development of the placenta. By studying a select group of three genes in further detail, the team went on to show that the death of the embryo could be directly linked to defects in the placenta in one out of these three cases. This may mean that a significant number of genetic defects that lead to prenatal death may be due to abnormalities of the placenta, not just the embryo.
Although this research uses mice, the findings are likely to be highly relevant to complications during human pregnancy and the study highlights the need for more work to be done on investigating development of the placenta during human pregnancies.
The placenta is vital for normal pregnancy progression and embryo development in most animals that give birth to live young, including humans. It provides a unique and highly specialised interface between the embryo and the mother, ensuring an adequate provision of nutrients and oxygen to the embryo. The placenta is also involved in waste disposal from the embryo and produces important hormones that help sustain pregnancy and promote foetal growth. Although previous research has highlighted the pivotal role of the placenta for a healthy pregnancy, its potential contribution to pregnancy complications and birth defects continues to be overlooked.
Scientists call mutations that cause death in the womb embryonic lethal. Mouse lethal genes are enriched for human disease genes and the affected embryos often show morphological abnormalities, i.e. changes to their shape and structure. Around one-third of all gene mutants studied in mouse are lethal or subviable (i.e. mutant offspring are less likely to survive than non-mutant pups).
“Analysis of embryonic lethal mutants has largely focused on the embryo and not the placenta, despite its critical role in development. Of the mutations we’ve studied, far more than expected showed defects in the placenta and this is particularly true for mutations that cause death during the early stages of pregnancy. Intriguingly, our analysis also indicates that issues in the placenta often occur alongside specific defects in the embryo itself.”
“Our data highlight the hugely under-appreciated importance of placental defects in contributing to abnormal embryo development and suggest key molecular nodes governing placentation. The importance of a healthy placenta has often been overlooked in these studies and it is important that we start doing more to understand its contribution to developmental abnormalities.”
Wellcome Sanger Institutewww.sanger.ac.uk/news/view/placenta-defects-critical-factor-prenatal-deaths