Previous research suggested that maternal vitamin D passes passively across the placenta, but the current study challenges this opinion.
“Research in the kidney has questioned the role of passive diffusion in vitamin D absorption. Instead, it has shown that this absorption is primarily driven by vitamin D’s intracellular process, where this vitamin is bound to the albumin-binding protein and taken up into organ tissue. Dr Claire Simner, Research Assistant at the University of Southampton, UK explains.
Simner was the first co-author of the study with Dr Brogan Ashley, who was also at the University of Southampton at the time the work was done. “We propose that a similar intracellular mechanism exists in the placenta, suggesting that this organ plays an active role in fetal vitamin D delivery.”
To further explore this idea, the team designed a study to understand how maternal vitamin D is absorbed, metabolized, and mediates gene expression inside the human placenta. They used an infusion model – which involves the use of samples of human placenta collected from full-term pregnancies immediately after birth – and cultured placental fragments to study the behavior of organ tissue. . These approaches contrast with the cellular modeling approaches of previous research on how vitamin D crosses the placenta.
To determine the placenta’s mechanism of vitamin D absorption, the team incubated fresh human placental fragments with vitamin D along with albumin for eight hours. They then analyzed the gene expression of the fragments using a technique called quantitative rtPCR.
Their analysis showed a significant increase in the expression of the CYP24A1 gene – which is involved in the control of vitamin D levels in the body – in the fragments after incubation, compared with fragments incubated with vitamin D alone. This suggests that albumin may help with vitamin D absorption.
“These findings suggest that endocytosis may play an important role in the absorption of vitamin D into the human placenta, as previously observed in the kidney.” Dr Jane Cleal, Lecturer in Genetics at the University of Southampton, and co-author of the study with Professor Nicholas Harvey, Professor of Rheumatology and Clinical Epidemiology at the Center for Living Pathological Epidemiology MRC, University of Southampton.
In addition, the team demonstrated that vitamin D exposure leads to rapid effects on the entire set of messenger RNA molecules (transcriptomes) and proteins (proteomes) expressed by the placenta.
Their results reveal that the underlying epigenetic landscape of the placenta – the interaction between genes and the environment – helps determine this transcriptional response to vitamin D treatment.
“This is the first quantitative study to demonstrate active metabolism and metabolism of vitamin D across the human placenta, with widespread effects on the placenta itself.” Dr. Clear concludes.
“Since our data were generated only from term placentas, additional studies are needed to determine how our findings relate to earlier stages of pregnancy. Insights from our work and future research will be helpful to identify potential new options for targeted interventions to improve pregnancy outcomes.”