RESUMEN
Nutrient sulfate is important for fetal development. The fetus has a limited capacity to generate sulfate and relies on maternal sulfate supplied via the placenta. The gestational age when fetal sulfate generation begins is unknown but would require cysteine dioxygenase (CDO1) which mediates a major step of sulfate production from cysteine. We investigated the ontogeny of Cdo1 mRNA expression in mouse fetal and placental tissues, which showed increasing levels from embryonic day 10.5 and was localised to the decidua and several fetal tissues including nasal cavities and brain. These findings suggest a role for Cdo1 in sulfate generation from mid-gestation.
Asunto(s)
Cisteína-Dioxigenasa/genética , Feto/metabolismo , Expresión Génica , Placenta/metabolismo , Animales , Encéfalo/metabolismo , Cisteína-Dioxigenasa/metabolismo , Femenino , Ratones , EmbarazoRESUMEN
Sulfate is an important nutrient for fetal growth and development. The fetus has no mechanism for producing its own sulfate and is therefore totally reliant on sulfate from the maternal circulation via placental sulfate transport. To build a model of directional sulfate transport in the placenta, we investigated the relative abundance of the 10 known sulfate transporter mRNAs in human placenta from uncomplicated term pregnancies. SLC13A4 and SLC26A2 were the most abundant sulfate transporter mRNAs, which localized to syncytiotrophoblast and cytotrophoblast cells, respectively. These findings indicate important physiological roles for SLC13A4 and SLC26A2 in human placental sulfate transport.
Asunto(s)
Proteínas de Transporte de Anión/biosíntesis , Placenta/metabolismo , Simportadores/biosíntesis , Trofoblastos/metabolismo , Transporte Biológico , Femenino , Humanos , Embarazo , ARN Mensajero/metabolismo , Transportadores de Sulfato , Sulfatos/metabolismo , TranscriptomaRESUMEN
The human solute linked carrier (SLC) 13A4 gene is primarily expressed in the placenta where it is proposed to mediate the transport of nutrient sulfate from mother to fetus. The molecular mechanisms involved in the regulation of SLC13A4 expression remain unknown. To investigate the regulation of SLC13A4 gene expression, we analysed the transcriptional activity of the human SLC13A4 5'-flanking region in the JEG-3 placental cell line using luciferase reporter assays. Basal transcriptional activity was identified in the region -57 to -192 nucleotides upstream of the SLC13A4 transcription initiation site. Mutational analysis of the minimal promoter region identified Nuclear factor Y (NFY), Specificity protein 1 (SP1) and Krüppel like factor 7 (KLF7) motifs which conferred positive transcriptional activity, as well as Zinc finger protein of the cerebellum 2 (ZIC2) and helix-loop-helix protein 1 (HEN1) motifs that repressed transcription. The conserved NFY, SP1, KLF7, ZIC2 and HEN1 motifs in the SLC13A4 promoter of placental species but not in non-placental species, suggests a potential role for these putative transcriptional factor binding motifs in the physiological control of SLC13A4 mRNA expression.