A placenta model, developed at the University of Cambridge, is enabling scientists to better understand the underlying cause of reproductive disorders.
Common disorders of pregnancy, such as pre-eclampsia, can often be traced back to abnormal placental development. Despite the fact that abnormal development of the placenta is a leading cause of maternal and fetal death, conducting research on the early stages of human pregnancy remains ethically and logistically challenging.
'Most of the major disorders of pregnancy – pre-eclampsia, stillbirth, growth restriction, for example – depend on failings in the way the placenta develops in the first few weeks,' said corresponding author Professor Ashley Moffett, from the University of Cambridge. 'This is a process that is incredibly difficult to study – the period after implantation, when the placenta embeds itself into the endometrium, is often described as a "black box of human development".'
In hopes of gaining a more mechanistic understanding of how reproductive disorders occur, Professor Moffett and colleagues at the Friedrich Miescher Institute, Basel, Switzerland and the Wellcome Sanger Institute, near Cambridge, used 'mini-placentas' to model early placental development.
The study, published in Cell Stem Cell details how 'trophoblast organoids' grown from placenta cells were used to better understand interactions between cells of the placenta and cells of the endometrium. The trophoblast is the outermost layer of the developing embryo, and is responsible for placenta formation.
Following up on previous work that highlighted the importance of immune cells called 'uterine natural killer cells' in mediating these interactions, this study simulated the in vivo conditions of placental implantation. In doing so, researchers were able to pinpoint specific proteins that facilitate the invasion of placental cells in the uterus.
'If the cells aren't able to invade properly, the arteries in the womb don't open up and
so the placenta – and therefore the baby – are starved of nutrients and oxygen,' explained Professor Moffett. 'That's why you get problems later on in pregnancy, when there just isn't enough blood to feed the baby.'
Researchers from this study are not alone in their efforts to develop a placenta model that can improve our understanding of reproductive disorders. In July of 2023, researchers at the University of Dundee developed 3D models of the human placenta grown from induced pluripotent stem cells (see BioNews 1199). Unlike the placental organoids used in this study, which are derived from first-trimester placental tissue, placenta models grown from stem cells are derived from human skin cells and bypass the need to obtain placental tissue.
Further studies using placenta models such as these may provide important insights into the cause of reproductive disorders.
Speaking about this latest study, Dr Margherita Turco, from the Friedrich Miescher Institute in Switzerland, stated that this work with 'mini-placentas' shows 'the power of basic science in helping us understand our fundamental biology, something that we hope will one day make a major difference to the health of mothers and their babies.'
Sources and References
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Human uterine natural killer cells regulate differentiation of extravillous trophoblast early in pregnancy
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'Mini-placentas’ help scientists understand the causes of pre-eclampsia and pregnancy disorders
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Cambridge lab grows 'mini-placentas' for pre-eclampsia study
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'Mini-Placentas' shine light on the cause of pre-eclampsia
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Scientists devise 'mini-placentas' to study early stages of pregnancy
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