Sulphate is an important nutrient for growth and development. During pregnancy, sulphate transporters in the maternal kidney (SLC13A1) and placenta (SLC13A4) are critical for sulphate supply to the fetus. The importance of maternal sulphate supply is relevant to preterm infants that rapidly become sulphate deficient. Accordingly, sulphate replacement therapies could potentially provide developmental benefits for preterm infants. However, we first need to identify an animal model that has similar sulphate physiology to humans before we consider preclinical sulphate interventional studies.
We investigated sulphate status in the preterm piglet as a potential model of the human preterm infant, including: (1) tissue distribution of SLC13A1 and SLC13A4 mRNA expression in the adult female pig; (2) plasma sulphate levels in pregnant and non-pregnant sows, and in preterm piglets; and (3) compared those data to published human findings. Pig SLC13A1 mRNA was expressed in kidney and ileum, whereas SLC13A4 mRNA was abundant in the placenta and brain, similar to human. Both genes share similar gene structure (SLC13A1 has 15 exons; SLC13A4 has 16 exons) to the human orthologues. In addition, pig SLC13A1 and SLC13A4 amino acid sequences share high homology, 87 and 90% respectively, with human sequences. Plasma sulphate levels in non-pregnant (1.02±0.17 mmol/L, mean±SD) and pregnant sows (0.75±0.23mmol/L) were approximately 3-fold higher than published human values, suggesting a high requirement for sulphate in pig physiology. Sulphate levels in preterm piglets at birth (0.93±0.17 mmol/L) were decreased to 0.77±0.20mmol/L by 8 hours post-delivery (P<0.01), which is consistent with depleting plasma sulphate levels in human neonates.
This study showed conserved sulphate transporter gene expression profiles between pig and human, as well as decreasing plasma sulphate levels in the preterm piglet. These findings suggest that the pig is most likely an appropriate model for testing sulphate replacement therapies, which is the next phase of this research.