Palmitic acid impairs human and mouse placental function by inhibiting trophoblast autophagy through induction of acyl-coenzyme A-binding protein (ACBP) upregulation

作者：Yi Zhang, Ling‐Ling Ruan, Mingrui Li, Yao Lü, Fangfang Li, You‐Long Xie, Jing Tang, Qian Feng, Xiao-Yan Chen, Yu‐Bin Ding, Lijuan Fu · 发表于：Human Reproduction · 年份：2024 · DOI：10.1093/humrep/deae091 · 被引用次数：12 · 研究领域：Prenatal Substance Exposure Effects、Lipid metabolism and biosynthesis、Fatty Acid Research and Health

STUDY QUESTION: Can exposure to palmitic acid (PA), a common saturated fatty acid, modulate autophagy in both human and mouse trophoblast cells through the regulation of acyl-coenzyme A-binding protein (ACBP)? SUMMARY ANSWER: PA exposure before and during pregnancy impairs placental development through mechanisms involving placental autophagy and ACBP expression. WHAT IS KNOWN ALREADY: High-fat diets, including PA, have been implicated in adverse effects on human placental and fetal development. Despite this recognition, the precise molecular mechanisms underlying these effects are not fully understood. STUDY DESIGN, SIZE, DURATION: Extravillous trophoblast (EVT) cell line HTR-8/SVneo and human trophoblast stem cell (hTSC)-derived EVT (hTSCs-EVT) were exposed to PA or vehicle control for 24 h. Female wild-type C57BL/6 mice were divided into PA and control groups (n = 10 per group) and subjected to a 12-week dietary intervention. Afterward, they were mated with male wild-type C57BL/6 mice and euthanized on Day 14 of gestation. Female ACBPflox/flox mice were also randomly assigned to control and PA-exposed groups (each with 10 mice), undergoing the same dietary intervention and mating with ACBPflox/floxELF5-Cre male mice, followed by euthanasia on Day 14 of gestation. The study assessed the effects of PA on mouse embryonic development and placental autophagy. Additionally, the role of ACBP in the pathogenesis of PA-induced placental toxicity was investigated. PARTICIPANTS/MATER...