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Vitamin D supplementation in pregnancy leads to altered gene signals in the baby

Published: 21 November 2018
Vitamin D supplementation in pregnancy leads to altered gene signals in the baby

Vitamin D supplementation in pregnancy could change the way a baby’s genes works to regulate vitamin D and bone health, a new University of Southampton study has shown.

Researchers from the Medical Research Council (MRC) Lifecourse Epidemiology Unit (LEU) and the Institute of Developmental Sciences (IDS) at the University of Southampton, who are also part of the EpiGen Consortium, investigated whether vitamin D supplementation in pregnancy might influence whether a gene involved in bone health and vitamin D signalling is switched on or off. The team studied a gene called RXRA, which has previously been identified as being linked with vitamin D status and offspring bone mass in a large mother-offspring cohort, the Southampton Women’s Survey.

The results, published in the Journal of Bone and Mineral Research, provide an insight into the influence of vitamin D on early determinants of skeletal growth, and improve the understanding of how osteoporosis could be prevented in future generations.

There is increasing evidence to suggest that the switching on and off of genes in particular human cells can change throughout life and can be affected by a range of environmental factors before birth, such as their parents’ health, diet and lifestyle before conception and during pregnancy. This switching on or off of genes is known as epigenetic modification.

An important epigenetic mechanism is DNA methylation, a crucial way of regulating biological processes which can last into adulthood. Rather like the addition of punctuation altering the meaning of a sentence, the epigenetic marks made on the DNA bases (often cyostine) change how it is converted into protein and what the cell can do.

The Southampton researchers, alongside collaborators from Oxford and Sheffield Universities, analysed the levels of DNA methylation in umbilical cord tissue of 453 babies born in the MAVIDOS Maternal Vitamin D Osteoporosis trial, a randomised controlled trial of vitamin D supplementation (1000 IU cholecalciferol daily) from the 14th week of pregnancy.

They compared the DNA methylation levels in the RXRA gene in babies born to mothers who had received a daily Vitamin D supplement through pregnancy and compared them with those born to mothers who received a placebo tablet daily. They also analysed DXA bone densitometry data, performed on the babies shortly after birth.

They found that vitamin D supplementation was linked to lower DNA methylation in particular parts of the RXRA gene, which is known to play a role in vitamin D signalling. They also saw associations between methylation at the RXRA gene and the baby’s bone mass– these findings will be explored in more detail as the children of the MAVIDOS trial grow up.

Nicholas Harvey, Professor of Rheumatology and Clinical Epidemiology at the MRC LEU, University of Southampton, led the study with Dr Elizabeth Curtis, Wellcome Trust Clinical Research Fellow, and Nevena Krstic, PhD student.

He said: “The health of a child’s bones when they are young can influence the risk of osteoporosis in older age. For the first time in a randomised trial setting, this study provides exciting insights into the role of vitamin D and epigenetics in bone health, and might allow us to more accurately predict an individual’s future risk of osteoporosis. Our ongoing studies should enable us to work out whether vitamin D supplementation will lead to persistent epigenetic changes, and lead to improved bone health in the offspring.”

Professor Cyrus Cooper, Director of the MRC LEU, said: "This major finding links our previous observations on maternal nutrition and lifestyle during pregnancy with the later risk of musculoskeletal ageing in the offspring. This work forms part of a larger programme of research at the MRC Lifecourse Epidemiology Unit, University of Southampton, addressing the early life determinants of bone development, and will inform novel strategies aimed at improving bone health across future generations.”

This latest study is another example of how the health of parents before and during pregnancy can affect the health of their baby. This will be the topic of debate at a Question Time-style event on Wednesday 21 November entitled ‘Fake Food’.

The event, organised by the IDS, will include a panel of experts taking audience questions and discussing the big food issues that matter from the very earliest points of development and across the life course. It is a free event which anyone can attend.


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