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. 2018 Nov 30;8:17492. doi: 10.1038/s41598-018-35681-0

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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(a) Diagrams showing the significant biological processes in which dysregulated proteins were involved, according to Panther classification system. Proteins up and down-regulated have been analyzed separately. Metabolic processes, developmental functions and cellular component organization or biogenesis were enriched in all conditions. (b) Histogram presenting the most enriched sub-functions of metabolic processes following STRING software analysis of all dysregulated proteins after 1 and 2 days of prenatal ATRA treatment. 76 dysregulated proteins following ATRA treatment were involved in metabolic processes. Red bars represented the number of up-regulated proteins, the green bars the down-regulated ones. (c) «Protein Synthesis, Cell Death and Survival, Cancer» network. According to IPA analysis, it was one of the major network in which proteins dysregulated by antenatal ATRA (after both one and 2 days) are involved. Up-regulated proteins are framed in red and down-regulated proteins in green. (d) HIF1A and its network from IPA analysis of proteomics data. Up-regulated proteins are in red and down-regulated proteins in green. In orange, HIF1A is predicted to be activated at E10.5 (1 day of ATRA 100-treatment). The orange arrows referred to activation, whereas yellow arrows evoked an inconsistent finding with state of downstream molecule. The stars highlighted proteins dysregulated in the same way after 1 and 2 days of ATRA-100 treatment.