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Understanding the impact of placental aging on placental function


Project Description

Prolonged pregnancy (>41 weeks gestation) is associated with an increase in perinatal mortality (the death of a baby before or shortly after birth) from a nadir of 1 per 1,000 births at 39 weeks’ to 3 per 1,000 births at 41 weeks which continues to rise beyond this time. However, the reasons underpinning this increase in risk are unknown. One possible explanation is a reduction in function of the placenta, the transient organ responsible for transfer of oxygen and nutrients to the developing fetus, due to ageing processes. In support of this hypothesis there is increased apoptosis and aggregates of effete nuclei in placental villi of prolonged pregnancies. However, others have questioned the concept of placental ageing.

This project will directly address the hypothesis that prolonged pregnancy is associated with altered cell turnover, favouring cell death rather than proliferation, and reduced metabolic activity and hormone synthesis compared to pregnancies ending at 39 weeks’ gestation. The secondary hypothesis is that, if present, these changes will be accompanied by changes consistent with ageing. The student will obtain placental tissue (using the local biobank) to compare apoptosis, proliferation, density of syncytial knots, vascularity, trophoblast area and inflammation in placental villi using established techniques in the laboratory. Biomarkers of ageing and senescence will be assessed using immunohistochemical staining. Placental mitochondrial function will be assessed in fresh tissue using an Oroboros oxygraph which assesses activity of the electron transport chain. Hormone release will be measured in conditioned culture medium from placental explants.

Training/techniques to be provided:
Training will be provided in placental sampling, immunohistochemical techniques, use of oxygraph and tissue culture. The laboratory also has significant expertise in placental perfusion, wire myography and nutrient uptake experiments which would allow these techniques to be considered for the doctoral programme of work.

Entry Requirements:
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area / subject. Candidates with experience in reproductive biology or with an interest in ageing are encouraged to apply.

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk

Funding Notes

Applications are invited from self-funded students. This project has a Band 3 fee. Details of our different fee bands can be found on our website (View Website). For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (View Website).

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

1. Heazell AEP, Newman L, Lean SC, Jones RL. Pregnancy outcome in mothers over the age of 35. Curr Opin Obstet Gynecol. 2018 Dec;30(6):337-343.
2. Lean SC, Heazell AEP, Dilworth MR, Mills TA, Jones RL. Placental Dysfunction Underlies Increased Risk of Fetal Growth Restriction and Stillbirth in Advanced Maternal Age Women. Sci Rep. 2017 Aug 29;7(1):9677
3. Ptacek I, Smith A, Garrod A, Bullough S, Bradley N, Batra G, Sibley CP, Jones RL, Brownbill P, Heazell AE. Quantitative assessment of placental morphology may identify specific causes of stillbirth. BMC Clin Pathol. 2016 Feb 9;16:1.

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