Transcriptome‐wide profile of 1α,25 dihydroxyvitamin D₃ in HTR‐8/SVneo cells

Abstract

Aim Vitamin D3 has been implicated in multiple reproductive events, whereas the effect of its bioactive metabolite 1α, 25 dihydroxyvitamin D3 (1,25(OH) 2D3) on transcriptome profile of the placenta is unclear. The aim of this article is to determine transcriptome‐wide profile caused by 1,25(OH) 2D3 in human placental trophoblast cells. Methods We performed RNA sequencing after stimulation of HTR‐8/SVneo cells with 0.1, 1, 10, and 100 nM 1,25(OH)2D3 for 24 h, identified differentially expressed genes by edgeR package (version 3.38.4), and analyzed Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways by webtool Metascape. Also, common genes and specific genes in different concentrations of 1,25(OH) 2D3 were identified. Results There were 180, 158, 161, and 174 differentially expressed genes after 0.1, 1, 10, and 100 nM 1,25(OH) 2D3 stimulation, respectively. KEGG pathway analysis displayed that “lipid and atherosclerosis” were significantly enriched at 0.1 and 1 nM 1,25(OH)2D3, while “cytokine‐cytokine receptor interaction,” “TGF‐beta signaling pathway” and “hippo signaling pathway” were significantly enriched in 1, 10, and 100 nM 1,25(OH)2D3. CYP24A1 was a significantly expressed common gene. UCP3 was significantly expressed in low concentrations and might affect energy metabolism. TCF24, EIF3CL, ABCD2, EPHA7, CRLF1, and SECTM1 were specific genes at physiological concentration. Similarly, SPDYE1, IQUB, IL18R1, and ZNF713 were considered as specific genes at supraphysiological concentration. Conclusions 1,25(OH)2D3 mainly affected the expression of CYP24A1 gene in HTR‐8/SVneo cells. Specific genes accounted for the majority of differentially expressed genes at different concentrations. However, their functions need to be further confirmed.