skip to primary navigationskip to content

Major scientific milestones

Listed here are contributions from the CTR that have had a major impact on our understanding of trophoblast and placental biology. A full list of papers published by members of the CTR is available at Publications.


The first molecular evidence demonstrating heterogeneity of placental pathology in cases of pre-eclampsia. Placental stress responses pathways are strongly activated in cases of early-onset pre-eclampsia, whereas placentas from late-onset cases (>34 weeks) are almost indistinguishable from normal controls. These data indicate a contrasting role of the placenta in causation of the two forms of the syndrome. Link

Magda Zernicka-Goetz creates a major breakthrough by developing an in vitro system enabling implantation of the blastocyst to be visualized and recorded in real time. The technique opens possibilities or understanding morphogenetic aspects of blastocyst development during implantation, and interactions with extracellular matrices. Link

Jens Kieckbusch and Louise Gaynor, working with Francesco Colucci and Ashley Moffett, provide compelling evidence that uterine Natural Killer cells play a key role in establishing the blood supply to the placenta. Inhibition of these cells during implantation in the mouse leads to compromised remodeling of the uterine spiral artery supplying the placenta and reduced fetal growth. Link



Another first!..some compelling evidence of a role for the placenta in programming of adult life. Increased reactivity to anxiety-provoking stimuli is manifest later in life only in those animals where there is a mismatch between placental supply and fetal demand for nutrients during gestation. These findings further distinguish placental dysfunction from IUGR, and reveal a novel role for the placenta on long term programming of emotional behaviour. Link

The first demonstration that endoplasmic reticulum stress can lead to reduced energy levels through impairment of mitochondrial function. Inhibition of protein synthesis by stress-response pathways is associated with reduced levels and activities of complexes in the electron transport chain. These effects are seen in placentas from pregnancies at high altitude, and may contribute to the accompanying growth restriction. Link

Hydrogen sulphide and the placenta; first demonstration that hydrogen sulphide is a potent vasodilator of the fetal circulation in the human placenta, and that the enzyme responsible for its production in the smooth muscle around stem villus arteries is reduced in pathological placentas associated with increased umbilical vascular resistance. Link


First experimental evidence that endoplasmic reticulum stress can lead to placental dysmorphogenesis, and that this is associated with loss of multipotency of trophoblast stem cells secondary to reduced bioactivity of key growth factors. This may be one mechanism by which placental stress results in growth restriction of the fetus. Link

First identification that oxidative stress in the fetal cardiovascular system is the mechanism through which developmental hypoxia programmes both cardiac and vascular disease in later life, providing not only an insight to mechanism but also possible targets for clinical intervention. Link


First identification that interactions between paternal antigens on the invading trophoblast cells and receptors on the maternal immune cells (uterine Natural Killer cells) affect the blood flow to the fetus, and hence pup weight, in the mouse. This study confirmed the importance of immunological crosstalk for normal physiological function of the placenta, and the importance of immunological interactions for the developmental programming of adult Link

Demonstration that a low protein maternal diet influences gene expression in the pancreas of the rat fetus in utero, predisposing to type 2 diabetes in later life. This study identified a fundamental mechanism by which poor fetal nutrition, during critical periods of development, interacts with the genome to influence long-term health, and has major relevance for the current epidemic of diabetes. Link

First direct evidence of developmental mechanisms that limit total demand for maternal nutrients during fetal overgrowth. Prior to this study nothing was known about the relationship between the placenta and the fetus in the situation of genetically determined overgrowth. This work shows that feto-placental signals are in operation to avoid excess drainage of maternal resources that might otherwise compromise fetal viability and future maternal reproductive success. This work has important implications to our understanding of fetal overgrowth, as large-for-gestation age infants are becoming more common in many parts of the world. Link


Publication of 'The Human Placenta and Developmental Programming'. This is the first text to explore the association between placental development and function, and the risk of developing chronic disease in later adult life. Link

First direct evidence that adverse maternal-fetal immunological interactions are associated with complications of human pregnancy, such as miscarriage, intrauterine growth restriction and pre-eclampsia. This study identified that certain combinations of antigens on the invading trophoblast cells and receptors on the uterine Natural Killer cells appear to place the pregnancy at risk. Link

First identification of an epigenetically regulated trophoblast stem cell compartment in the human early placenta. This study demonstrated the presence of a population of highly proliferative cytotrophoblast cells positive for the transcription factor ELF5 over the villous surface and at the proximal end of the cytotrophoblast cell columns. Link


First demonstration that some nuclei within the syncytiotrophoblast are transcriptionally active, shedding new insight into how this critical tissue is able to adapt rapidly to changes in the intrauterine environment. Link


First identification of the molecular mechanism underlying the differentiation of trophoblast cells in the mouse. This study demonstrated that the transcription factor, ELF5, creates a positive-feedback loop with trophoblast stem cell determinants, but is repressed by methylation in the cells of the embryo. Link

First demonstration of endoplasmic reticulum stress as a major component of the placental pathology in complications of pregnancy associated with intrauterine growth restriction and low birth weight. This study provides a molecular mechanism for the reduced cell proliferation seen in these pregnancies, opening new avenues for therapies. Link

Publication of 'Comparative placentation; structures, functions and evolution', a monograph providing details on placental structures from sharks and fishes through to higher primates and man. Link