Placenta plays active part in transferring vitamin D to fetus during
pregnancy

Date:
March 8, 2022
Source:
eLife
Summary:
Scientists have shed new light on the role of the placenta in
managing the relationships between maternal vitamin D and fetal
development, according to a new study.



FULL STORY ========================================================================== Scientists have shed new light on the role of the placenta in managing
the relationships between maternal vitamin D and fetal development,
according to a study published today in eLife.


==========================================================================
The findings demonstrate a complex interplay between vitamin D and the placenta, and could help inform future interventions using vitamin D to
support fetal development and maternal adaptations to pregnancy.

As vitamin D is unable to be produced by a fetus, it must be transferred
across the placenta. This is important for both fetal and lifelong
health. Maternal vitamin D concentrations are positively associated with
fetal bone growth and birth weight, and these associations continue into postnatal life.

Previous work has suggested that maternal vitamin D transfers passively
across the placenta, but the current study challenges this idea.

"Research in kidneys has questioned the role of passive diffusion in
the uptake of vitamin D. It has instead shown that this uptake is driven primarily by endocytosis of vitamin D, where the vitamin is bound to the binding protein albumin and introduced into the organ tissue cells,"
explains Dr Claire Simner, Research Assistant at the University of
Southampton, UK. Simner is a co-first author of the study alongside Dr
Brogan Ashley, who was also at the University of Southampton at the time
the work was carried out. "We proposed that a similar endocytic mechanism exists in the placenta, suggesting that this organ plays an active role
in the delivery of vitamin D to the fetus." To explore this idea further,
the team designed a study to find out how maternal vitamin D is taken up, metabolised and mediates gene expression within the human placenta. They
used a perfusion model -- involving the use of human placental samples collected from term pregnancies immediately after delivery - - and
placental fragment cultures to study the behaviour of the organ tissue.

These methods contrast with cell-model approaches of previous research
into how vitamin D transfers across the placenta.

To determine the mechanisms of placental vitamin D uptake, the team
incubated fresh term human placental fragments with vitamin D alongside
albumin for eight hours. They then analysed the gene expression of the fragments using a technique called quantitative rtPCR. Their analysis
revealed a significant increase in the expression of the CYP24A1 gene --
which is involved in controlling the amount of vitamin D in the body --
in the fragments following incubation, compared to fragments that were incubated with vitamin D only. This suggests that albumin might enable
vitamin D uptake.

"These findings show that endocytosis may play an important role in the
uptake of vitamin D into the human placenta, as previously seen in the kidneys," says Dr Jane Cleal, Lecturer in Epigenetics at the University
of Southampton, and a co-senior author of the study alongside Professor Nicholas Harvey, Professor of Rheumatology and Clinical Epidemiology at
the MRC Lifecourse Epidemiology Centre, University of Southampton.

Additionally, the team demonstrated that vitamin D exposure leads to rapid effects on the full set of messenger RNA molecules (the transcriptome)
and of proteins (the proteome) expressed by the placenta. Their results revealed that the underlying epigenetic landscape of the placenta --
the interaction between the genes and the environment -- helps to dictate
this transcriptional response to vitamin D treatment.

"This is the first quantitative study demonstrating the active transfer
and metabolism of vitamin D by the human placenta, with widespread effects
on the placenta itself," Dr Cleal concludes. "As our data are generated
from term placenta only, additional studies are needed to determine
how our findings relate to earlier stages of gestation. Together,
the insights from our work and future research will be helpful for
identifying potential new options for targeted interventions to improve pregnancy outcomes."

========================================================================== Story Source: Materials provided by eLife. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Claire Simner, Brogan Ashley, Antigoni Manousopoulou, Carl
Jenkinson,
Felicity Hey, Jennifer M Frost, Faisal I Rezwan, Cory H White,
Emma M Lofthouse, Emily Hyde, Laura DF Cooke, Sheila Barton,
Pamela Mahon, Elizabeth M Curtis, Rebecca J Moon, Sarah R Crozier,
Hazel M Inskip, Keith M Godfrey, John W Holloway, Cyrus Cooper,
Kerry S Jones, Rohan M Lewis, Martin Hewison, Spiros DD Garbis,
Miguel R Branco, Nicholas C Harvey, Jane K Cleal. Placental uptake
and metabolism of 25(OH)vitamin D determine its activity within
the fetoplacental unit. eLife, 2022; 11 DOI: 10.7554/eLife.71094 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220308115808.htm

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