Placental, Renal, and Ileal Sulfate Transporter Gene Expression in Mouse Gestation1

Abstract

Sulfate is important for mammalian growth and development. During pregnancy, maternal circulating sulfate levels increase by 2-fold, enhancing sulfate availability to the fetus. We used quantitative real-time PCR to determine sulfate transporter mRNA levels during mouse gestation in three tissues: kidney and ileum, to identify transporters involved in sulfate absorption and maintaining high maternal circulating sulfate level; and placenta, to build a model of directional sulfate transport from mother to fetus. In the kidney, Slc13a1 and Slc26a1 were the most abundant sulfate transporter mRNAs, which increased by ≈2-fold at E4.5 or E6.5, whereas lower levels of Slc26a2, Slc26a6, and Slc26a7 mRNA increased by ≈3- to 6-fold from E4.5. Ileal sulfate transporter mRNA levels were not increased in gestation, but slight decreases (by ≈30-40%) were found for Slc26a3 and Slc26a6. In placentae, Slc13a4 and Slc26a2 mRNAs were most abundant, with levels increasing from E10.5 and peaking (≈8-fold) from E14.5 to E18.5, whereas Slc26a1 increased by ≈3-fold at E18.5. The spatial expression of placental mRNAs was determined by in situ hybridization showing Slc13a4 and Slc26a6 in yolk sac, Slc26a1 in spongiotrophoblasts, and Slc13a4, Slc26a2, Slc26a3, and Slc26a7 in the labyrinthine layer. Within the labyrinth, cell-specific staining revealed Slc13a4 expression in syncytiotrophoblast-II (SynT-II) and Slc26a2 in SynT-I. Together, these data show kidney Slc13a1 and Slc26a1 and placental Slc13a4 and Slc26a2 to be the most abundant sulfate transporter mRNAs in mouse gestation, which likely play important physiological roles in maintaining high maternal serum sulfate levels during pregnancy and mediating sulfate supply to the fetus.

Loss of Rearranged L-Myc Fusion (RLF) results in defects in heart development in the mouse

“…Digoxigenin (DIG) labelled cRNA probes were synthesized in accordance with manufacturer's directions (Roche) and as previously described (Simmons et al, 2007). ISH on 10 µm paraffinembedded sections were undertaken as previously described (Dawson et al, 2012). Negative controls included the use of sense probes for all mRNA analysed, and positive controls included the detection of antisense probes in positive control tissues (See Supplementary Fig.…”

Loss of the sulfate transporter Slc13a4 in placenta causes severe fetal abnormalities and death in mice

“…The sulfate transporter SLC13A4 is expressed predominantly in the placenta, where it is proposed to mediate sulfate supply to the fetus [8]. Previously we examined the spatial localization of all 10 sulfate transporters in human [9] and mouse placenta [8] and identified Slc13a4 as the most abundant sulfate transporter localized to the transporting syncytiotrophoblasts. In the current study we describe the critical requirement of placental Slc13a4 activity for normal fetal development in mice.…”

The Biological Roles of Steroid Sulfonation

“…Recently, the relative abundance and cellular expression of all known placental sulfate transporters was described [91]. That study identified Slc13a4 (aka NaS2, Sodium sulfate transporter-2) to be the most abundant placental sulfate transporter, which was localised to the syncytiotrophoblasts of mouse placenta, where it is proposed to supply sulfate into the placenta from maternal circulation.…”