Fig. 8: KDM5C overexpression promotes embryo resorption in a mouse model.

Mouse trophoblast stem cells were transduced with adenovirus-mediated GFP (Ad-GFP) or adenovirus-mediated mouse KDM5C gene (Ad-KDM5C). Level of KDM5C (A, B), TGFβ2 and RAGE. (C, D) expression in trophoblast stem cells was detected through qRT-PCR assay at the mRNA level and western blotting at the protein level; C, n = 3 for each group. E Western blotting to determine the level of KDM5C expression in mouse placenta with Ad-GFP or Ad-KDM5C treatments. F, G Embryo-resorption rates in mice treated with Ad-GFP (n = 7) or Ad-KDM5C treatments (n = 11). Representative macroscopic imaging of uteri at gestational age E 11.5 in pregnancies that received various treatments. H Protein level of TGFβ2 and RAGE expression in mouse placenta with Ad-GFP or Ad-KDM5C treatments as determined by western blotting. I Level of TGFβ2 and RAGE mRNA detected in primary trophoblasts isolated from Ad-GFP- and Ad-KDM5C-injected mice were determined by qRT-PCR; n = 5 for each group. J In normal pregnancies, decreased expression of KDM5C is associated with higher H3K4me3 methylation in the promoters of target genes, such as TGFβ2 and RAGE, therefore promoting transcription of the TGFβ2 and RAGE gene, which keeps trophoblasts in a normal state of proliferation and invasion (Left). In RM, this signal transduction pathway is altered due to an increase in the expression of KDM5C, which binds to the promoters of certain target genes, such as TGFβ2 and RAGE, and reduces the local H3K4me3 constitutively to repress transcription of these target genes, ultimately resulting in inhibition of trophoblast invasion and proliferation and the development of RM (Right). dCCT distal cell column trophoblast; pCCT proximal cell column trophoblast; STB syncytiotrophoblast; vCTB villous cytotrophoblast; EVTs extravillous trophoblasts. Data are shown as the mean ± SEM; Student’s t test was used to evaluate the statistical significance; *p < 0.05.