Placenta is initiated first, as cells of a fertilised egg divide and specialise

September 24, 2020

The first stages of placental development take place days before the embryo starts to form in human pregnancies. The finding highlights the importance of healthy placental development in pregnancy, and could lead to future improvements in fertility treatments such as IVF, and a better understanding of placental-related diseases in pregnancy.

In a study published in the journal Nature, researchers looked at the biological pathways active in human embryos during their first few days of development to understand how cells acquire different fates and functions within the early embryo.*

They observed that shortly after fertilisation as cells start to divide, some cells start to stick together. This triggers a cascade of molecular events that initiate placental development. A subset of cells change shape, or 'polarise', and this drives the change into a placental progenitor cell - the precursor to a specialised placenta cell - that can be distinguished by differences in genes and proteins from other cells in the embryo.

"This study highlights the critical importance of the placenta for healthy human development," said Dr Kathy Niakan, group leader of the Human Embryo and Stem Cell Laboratory at the Francis Crick Institute and Professor of Reproductive Physiology at the University of Cambridge, and senior author of the study.

Niakan added: "If the molecular mechanism we discovered for this first cell decision in humans is not appropriately established, this will have significant negative consequences for the development of the embryo and its ability to successfully implant in the womb."

The team also examined the same developmental pathways in mouse and cow embryos.** They found that while the mechanisms of later stages of development differ between species, the placental progenitor is still the first cell to differentiate.

"We've shown that one of the earliest cell decisions during development is widespread in mammals, and this will help form the basis of future developmental research. Next we must further interrogate these pathways to identify biomarkers and facilitate healthy placental development in people, and also cows or other domestic animals," said Claudia Gerri, lead author of the study and postdoctoral training fellow in the Human Embryo and Stem Cell Laboratory at the Francis Crick Institute.

During IVF, one of the most significant predictors of an embryo implanting in the womb is the appearance of placental progenitor cells under the microscope. If researchers could identify better markers of placental health or find ways to improve it, this could make a difference for people struggling to conceive.

"Understanding the process of early human development in the womb could provide us with insights that may lead to improvements in IVF success rates in the future. It could also allow us to understand early placental dysfunctions that can pose a risk to human health later in pregnancy," said Niakan.
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The research was led by scientists at the Francis Crick Institute, in collaboration with colleagues at the Royal Veterinary College, Vrije Universiteit Brussel, Université de Nantes and Bourn Hall Clinic. Kathy Niakan is incoming Director of the University of Cambridge's Centre for Trophoblast Research, and Chair of the Cambridge Strategic Research Initiative in Reproduction.

The work was funded by the UK Medical Research Council, Wellcome and Cancer Research UK. It was approved by the UK Human Fertilisation and Embryology Authority (HFEA) and the Health Research Authority's Research Ethics Committee.

Notes to editors

Reference: Gerri, C. et al. (2020). Initiation of a conserved trophectoderm program in human, cow and mouse embryos. Nature. 10.1038/s41586-020-2759-x.

*The human embryos examined during this study were in the morula stage of early-development, consisting of around 16-32 cells before progressing into the blastocyst stage (around 200 cells). They had been donated to research with consent by people undergoing in vitro fertilisation (IVF) and were not needed during the course of their treatment.

This study was approved by the UK Human Fertilisation and Embryology Authority (HFEA): research licence number R0162, and the Health Research Authority's Research Ethics Committee (Cambridge Central reference number 19/EE/0297).

**Cow ovaries were obtained as surplus material from abattoirs and bull sperm was obtained from Genus ABS UK and UK Sire Services. This work was approved by the Ethics Committee at the Royal Veterinary College, and followed all relevant institutional and national guidelines and regulations.

Mice were mated under laboratory conditions and mouse fertilised eggs isolated for the purpose of this study. This study was approved by the Animal Ethics Committee and by the UK Home Office licence number 70/8560, and followed all relevant institutional and national guidelines and regulations.

The Francis Crick Institute is a biomedical discovery institute dedicated to understanding the fundamental biology underlying health and disease. Its work is helping to understand why disease develops and to translate discoveries into new ways to prevent, diagnose and treat illnesses such as cancer, heart disease, stroke, infections, and neurodegenerative diseases.

An independent organisation, its founding partners are the Medical Research Council (MRC), Cancer Research UK, Wellcome, UCL (University College London), Imperial College London and King's College London.

The Crick was formed in 2015, and in 2016 it moved into a brand new state-of-the-art building in central London which brings together 1500 scientists and support staff working collaboratively across disciplines, making it the biggest biomedical research facility under a single roof in Europe.

http://crick.ac.uk/

The Francis Crick Institute

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