139. PLACENTAL EXPRESSION OF microRNAs ALTERS WITH GESTATION IN THE GUINEA PIG

Functional development of the placenta ensures an adequate supply of nutrients for fetal growth throughout gestation. Placental nutrient transport capacity increases during gestation, through alterations in structure and abundance of its molecular determinants, including expression of Slc2a1 (glucose transporter type-1) and Slc38a2 (system A amino acid transporter), as well as Igf1and Igf2. Each of these genes are predicted targets of microRNAs. Non-coding RNAs can down-regulate, as well as activate translation, by interacting with complementary regions in the promoter, coding, or 3’UTR of target mRNAs.(1) MicroRNAs are present in the mammalian placenta,(2) but little is known about developmental changes in their expression and actions. We hypothesised that placental expression of microRNAs which target molecular mediators of nutrient transport changes during gestation. Expression of microRNAs in the guinea pig placenta was examined at D30 (n = 7) and D60 (n = 7) of gestation (term = D70) by Exiqon microarray. Gene expression was measured by real-time PCR. Predicted gene targets were identified using miRecords and networks and pathways by Ingenuity Pathway Analysis. Placental expression of 119 microRNAs was upregulated (P < 0.05), and that of 40 was down-regulated (P < 0.05), at late compared to early gestation. Of the 20 most abundant differentially up- or down-regulated microRNAs, 11 are predicted to target members of solute carrier families. This includes has-miR-26a (↑2X), which is predicted to target Slc38a2 mRNA and expression of has-miR-26a and Slc38a2 was positively correlated (P < 0.02). Alternate predicted targets of has-miR-26a include networks involving amino acid metabolism, molecular transport and small molecular biochemistry. These findings support the hypotheses that gestational changes in microRNA expression act to regulate functional development of the placenta, including expression of genes that mediate nutrient transport. (1) Breving K, Esquela-Kerscher A. Int J Biochem Cell Biol 2009.(2) Barad O, et al. Genome Res 2004 14: 2486–2494.