Sulfate is an important nutrient for fetal growth and development. The fetus has no mechanism for producing its own sulfate and is totally reliant on sulfate from the maternal circulation (1). In human and rodent gestation, maternal serum sulfate levels increase by 2-fold, enhancing sulfate availability to the fetus (2). This doubling of maternal serum sulfate levels is achieved via increased activity of the renal SLC13A1 sulfate transporter which reduces sulfate loss in the maternal urine, and increases blood sulfate levels (3). Maternal sulfate is then transported to the fetus by a related transporter (SLC13A4) in the placenta. We have shown reduced fecundity in Slc13a1 null mice (2,4) and are now investigating Slc13a4 null mice.
We identified SLC13A4 to be the most abundant placental sulfate transporter mRNA in both mice and humans. SLC13A4 mRNA was localised specifically to syncytiotrophoblast cells, where it is situated to mediate sulfate transport across the feto-maternal blood barrier. Slc13a4 null mice, from heterozygous Slc13a4 matings, have major developmental defects and die in late gestation. We observed significantly reduced litter sizes from heterozygous Slc13a4 matings (median = 5 pups, compared to 8 pups from heterozygous x wildtype matings), which cannot be solely attributed to loss of Slc13a4 null fetuses. This suggests reduced survival of some Slc13a4 heterozygous and wildtype littermates during pregnancy or at birth, and indicates a possible perturbation to maternal care.
Together, our studies in mice have further revealed the unappreciated roles of sulfate in fetal growth and survival, which have prompted us to investigate the role of sulfate transporters in pregnant women with altered sulfate homeostasis.
References: (1) Dawson 2011 Sem.Cell Devel.Biol. (2) Dawson et al. 2011 J.Reprod.Devel. (3) Dawson et al 2012 Biol.Reprod. (4) Dawson et al 2003 Proc.Natl.Acad.Sci.USA.