Abstract
Di-2-ethylhexyl phthalate (DEHP) has been proven to boost miR-155-5p level in trophoblasts, but how DEHP-induced miR-155-5p regulates trophoblastic functions is unclear. For in vivo experiments, DEHP was administered to pregnant Sprague-Dawley (SD) rats at various dosages. After birth, the development of rat fetuses was evaluated. The morphology of the placentae was evaluated using HE staining. miR-155-5p level in placentae was measured utilizing RT-qPCR. Placental cAMP/PKA pathway activation and lipid metabolism levels were assessed using WB, RT-qPCR, and ELISA. For in vitro experiments, DEHP, miR-155-5p inhibitor, or cAMP/PKA inhibitor were applied to treat HTR-8/Svneo cells. Cell viability and functions were investigated utilizing WB, RT-qPCR, CCK-8, transwell assay, plate colony formation assay, and flow cytometry. Besides, the cAMP/PKA pathway activation and lipid metabolism levels in HTR-8/Svneo cells were detected via ELISA, WB, and RT-qPCR. DEHP resulted in fetal malformations and abnormal placental histopathology. DEHP also promoted placental miR-155-5p expression, the cAMP/PKA inactivation, and lipid metabolism in placentae. miR-155-5p knockdown abrogated DEHP-induced proliferative, migrative, and invasive inhibition in HTR-8/Svneo cells. Moreover, miR-155-5p downregulation abolished DEHP-induced inactivation of the cAMP/PKA pathway and enhanced lipid metabolism. Additionally, DEHP-induced miR-155-5p facilitated lipid metabolism by inhibiting the cAMP/PKA signaling pathway in HTR-8/Svneo cells. The current study reveals that miR-155-5p plays an indispensable role in DEHP-induced trophoblastic toxicity by promoting lipid metabolism via inhibiting the cAMP/PKA signaling pathway, indicating miR-155-5p might be a promising therapeutic target for DEHP exposure during pregnancy.