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Impact of intermittent maternal fasting on placental calcium transport and fetal skeletal development

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  • Full or part time
    Dr J Glazier
    Dr N Ashton
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

Project Description

Many pregnant women fast during the holy month of Ramadan despite being exempt. As the fetus relies upon the mother for its supply of nutrients, fasting is likely to affect development of the fetus. Osteoporosis is recognised as a skeletal disorder that may be ‘programmed’ by nutritional events in pregnancy. A reduced childhood bone mass increases susceptibility to osteoporosis later in life; therefore acquisition of optimal bone mass and mineralisation is crucially important for bone health later in life.

Most fetal skeletal calcium accretion occurs over the last third of pregnancy, so fasting during this period is likely to have a marked impact on skeletal mineralisation. In rodents, fetal calcium accretion over this period is associated with a marked induction in the expression of the calcium binding protein, calbindin-D9k, in both the placenta and yolk sac. This increase in calbindin-D9k expression is mirrored by an increase in the rate of transplacental calcium transfer.

We have developed a rat model of intermittent fasting (IF) during pregnancy which mimics the pattern of fasting during Ramadan. The primary aim of this study is to investigate the impact of maternal IF on calcium accretion and skeletal development in the fetus. A secondary aim is to examine how maternal IF during pregnancy alters renal calcium transport, as the kidney expresses two isoforms of calbindin proteins, calbindin-D9k and calbindin-D28k. This project will therefore investigate the relationship between calbindin expression and calcium transport capacity in the placenta, yolk sac and kidney in order to determine whether calcium transport in utero is altered by maternal IF. The potential impacts on placental and renal calcium transport function, skeletal development and mineralisation of the skeleton will be determined.

This project interfaces with our current ongoing studies investigating how maternal IF fasting during pregnancy influences offspring metabolism, physiology and function.

Training/techniques to be provided:

This project will employ a variety of in vivo and in vitro techniques to investigate the project objectives including biochemical assays, yolk sac analysis, transplacental calcium flux measurements, placental vesicles, qPCR, immunohistochemistry, Western blotting, renal clearance measurements and offspring assays.

The project will involve the use of laboratory rats; therefore applicants must be comfortable with the use of animals in biomedical research. Full training will be provided and the successful candidate will be expected to pass a Home Office personal licensee training course.

Funding Notes

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a relevant biological/medical science, molecular biology or related discipline. A Masters qualification in a similar area and/or previous research experience would be advantageous. Candidates with experience of in vivo studies are encouraged to apply.

This project has a Band 3 fee. Details of our different fee bands can be found on our website (https://www.bmh.manchester.ac.uk/study/research/fees/). For information on how to apply for this project, please visit our website (https://www.bmh.manchester.ac.uk/study/research/apply/).

Informal enquiries may be made directly to the primary supervisor.

References

Glazier, J.D., Atkinson, D.E., Thornburg, K.L., Sharpe, P.T., Edwards, D., Boyd, R.D.H. & Sibley, C.P. (1992). Gestational changes in Ca2+ transport across rat placenta and mRNA for calbindin9K and CaATPase. American J. Physiology 263: R930-R935.

Glazier, J.D., Mawer, E.B. & Sibley, C.P. (1995).
Calbindin-D9K gene expression in rat chorioallantoic placenta is not regulated by 1,25 dihydroxyvitamin D3. Pediatric Research 37: 720-725.

Bond, H., Dilworth, M.R., Baker, B., Cowley, E., Requena Jimenez, A., Boyd, R.D.H., Husain, S.M., Ward, B.S., Sibley, C.P. & Glazier, J.D. (2008). Increased maternofetal calcium flux in PTHrP-null mice. J. Physiology 586.7: 2015-2025.



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