Temporal Changes in the Transcriptomic Profile of Granulosa Cells of Pigs Treated with 2,3,7,8-Tetrachlorodibenzo-p-dioxin.

The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) compound is an environmental chemical adversely affecting reproductive processes. Intracellular TCDD effects are mediated via aryl hydrocarbon receptor (AhR). The aim of the current study was to identify genes linking the AhR pathway with phenotypic consequences of TCDD action in granulosa cells of pigs. By applying multifactorial analysis, with TCDD and incubation time as factors, it was possible to determine temporal changes induced by TCDD in the cell transcriptome. Among the identified 144 differentially expressed genes (DEGs; Padjusted<0.05, log2 fold change (FC)≥1), 111 DEGs were classified as sustained genes (FC values changing between 3 and 24 h). Eighty six DEGs were classified as early genes and only nine as late genes (FC changes observed between 3 and 12 h or 12 and 24 h, respectively). The sustained gene category included genes related to TCDD mechanism of action (AHR, ARNTL, CYP1A1), cell proliferation (TGFβ3), follicular development and ovulation (PTGS2) as well as stress response (NR3C1). The early gene category contained DEGs associated with cell proliferation (DUSP4, TAB1) and cellular response to stress (DHX34). The CYP1A1 gene was the only DEG classified as an early, late and sustained gene. The multifactorial approach allowed for statistically analyzing TCDD-induced changes over time in the gene expression in granulosa cells of pigs. Changes over time in the granulosal transcriptome profile indicated the involvement of stress related molecules in the cellular response to TCDD and TCDD effects on ovulation. The TCDD effects were particularly evident during the early stage of action by this compound.