Resveratrol reliefs DEHP-induced defects during human decidualization

Abstract

Di-(2-Ethylhexyl) phthalate (DEHP) is widely used as an additive in many plastic products. Studies have revealed that DEHP persistent exposure can affect embryonic development and lead to adverse female reproductive disorders. The establishment of pregnancy involves extensive changes in the endometrial tissue, including massive extracellular matrix (ECM) remodeling. Decidualization of the endometrium provides a suitable environment for subsequent growth by causing changes in the morphology of the uterine stromal cells, is a key process in human pregnancy. Resveratrol (RSV) is a natural polyphenolic plant antitoxin with a wide range of pharmacological effects. Growing evidence indicates that RSV has therapeutic effects on certain female reproductive disorders. In this study, the effect of DEHP on cell viability was investigated by cell proliferation assay. Cell decidualization was induced in vitro, and the downregulation of molecules associated with decidualization was confirmed through quantitative real-time PCR and western blot analysis. Immunofluorescence analysis revealed alteration in cell morphology, and found that administration of DEHP sufficiently induced ERα entry into the nucleus. The effect of DEHP on cells was fully verified by RNA-seq analysis. Interestingly, an upregulation of decidual molecules was observed after rescue with RSV, which was confirmed by RNA-seq transcriptome analysis and quantitative real-time PCR assay. Additionally, the expression of ECM remodeling-related genes was significantly restored by RSV administration. The study revealed the potential mechanisms of DEHP-induced decidualization defects and the functional relieving roles of RSV while providing a perspective therapeutic candidate for alleviating the DEHP-induced deficiencies in decidualization.

Keywords: DEHP; Decidualization; ECM; Environmental pollutant; Resveratrol.