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/MATERIALS, SETTING, METHODS The findings were validated using real-time PCR, Western blot, immunofluorescence, transmission electron microscopy, and shRNA knockdown approaches. MAIN RESULTS AND THE ROLE OF CHANCE Exposure to PA-upregulated ACBP expression in both human HTR-8/SVneo cells and hTSCs-EVT, as well as in mouse placenta. PA exposure also induced autophagic dysfunction in HTR-8/SVneo cells, hTSCs-EVT, and mouse placenta. Through studies on ACBP placental conditional knockout mice and ACBP knockdown human trophoblast cells, it was revealed that reduced ACBP expression led to trophoblast malfunction and affected the expression of autophagy-related proteins LC3B-II and P62, thereby impacting embryonic development. Conversely, ACBP knockdown partially mitigated PA-induced impairment of placental trophoblast autophagy, observed both in vitro in human trophoblast cells and in vivo in mice. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Primary EVT cells from early pregnancy are fragile, limiting research use. Maintaining their viability is tough, affecting data reliability. The study lacks depth to explore PA diet cessation effects after 12 weeks. Without follow-up, understanding postdiet impacts on pregnancy stages is incomplete. Placental abnormalities linked to elevated PA diet in embryos lack confirmation due to absence of control groups. Clarifying if issues stem solely from PA exposure is difficult without proper controls. WIDER IMPLICATIONS OF THE FINDINGS Consuming a high-fat diet before and during pregnancy may result in complications or challenges in successfully carrying the pregnancy to term. It suggests that such dietary habits can have detrimental effects on the health of both the mother and the developing fetus. STUDY FUNDING/COMPETING INTEREST(S) This work was supported in part by the National Natural Science Foundation of China (82171664, 82301909) and the Natural Science Foundation of Chongqing Municipality of China (CSTB2022NS·CQ-LZX0062, cstc2019jcyj-msxmX0749, and cstc2021jcyj-msxmX0236). The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER N/A.

中文翻译：

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棕榈酸通过诱导酰基辅酶 A 结合蛋白 (ACBP) 上调抑制滋养层自噬，从而损害人类和小鼠胎盘功能

研究问题 接触棕榈酸 (PA)（一种常见的饱和脂肪酸）能否通过调节酰基辅酶 A 结合蛋白 (ACBP) 来调节人和小鼠滋养层细胞的自噬？摘要答案 妊娠前和妊娠期间 PA 暴露会通过涉及胎盘自噬和 ACBP 表达的机制损害胎盘发育。已知的情况 高脂肪饮食（包括 PA）会对人类胎盘和胎儿发育产生不利影响。尽管认识到这一点，但这些效应背后的精确分子机制尚未完全了解。研究设计、大小、持续时间将绒毛外滋养层 (EVT) 细胞系 HTR-8/SVneo 和人滋养层干细胞 (hTSC) 衍生的 EVT (hTSCs-EVT) 暴露于 PA 或载体对照中 24 小时。将雌性野生型 C57BL/6 小鼠分为 PA 组和对照组（每组 n = 10），并接受为期 12 周的饮食干预。随后，它们与雄性野生型 C57BL/6 小鼠交配，并在妊娠第 14 天处以安乐死。雌性 ACBPflox/flox 小鼠也被随机分配到对照组和 PA 暴露组（每组 10 只小鼠），接受相同的饮食干预并与 ACBPflox/floxELF5-Cre 雄性小鼠交配，然后在妊娠第 14 天实施安乐死。该研究评估了 PA 对小鼠胚胎发育和胎盘自噬的影响。此外，还研究了 ACBP 在 PA 诱导的胎盘毒性发病机制中的作用。参与者/材料、背景、方法 使用实时 PCR、蛋白质印迹、免疫荧光、透射电子显微镜和 shRNA 敲低方法验证了研究结果。主要结果和机会的作用 暴露于 PA 上调的人 HTR-8/SVneo 细胞和 hTSC-EVT 以及小鼠胎盘中的 ACBP 表达。 PA 暴露还会诱导 HTR-8/SVneo 细胞、hTSC-EVT 和小鼠胎盘中的自噬功能障碍。通过对ACBP胎盘条件性敲除小鼠和ACBP敲除人滋养层细胞的研究发现，ACBP表达减少导致滋养层功能障碍，影响自噬相关蛋白LC3B-II和P62的表达，从而影响胚胎发育。相反，在体外人类滋养层细胞和小鼠体内观察到，ACBP 敲低部分减轻了 PA 诱导的胎盘滋养层自噬损伤。大规模数据不适用。局限性和注意事项 妊娠早期的原代 EVT 细胞很脆弱，限制了研究用途。维持其生存能力非常困难，会影响数据可靠性。该研究缺乏深度探讨 12 周后 PA 饮食戒断的影响。如果没有后续行动，了解饮食后对怀孕阶段的影响是不完整的。由于缺乏对照组，与胚胎中高 PA 饮食相关的胎盘异常缺乏证实。如果没有适当的控制，很难澄清问题是否仅由 PA 暴露引起。研究结果的更广泛意义在怀孕前和怀孕期间食用高脂肪饮食可能会导致并发症或成功怀孕至足月的挑战。这表明这种饮食习惯会对母亲和发育中的胎儿的健康产生不利影响。研究经费/竞争利益 这项工作得到了国家自然科学基金 (82171664, 82301909) 和重庆市自然科学基金 (CSTB2022NS·CQ-LZX0062、cstc2019jcyj-msxmX0749 和 cstc2021jcyj) 的部分支持-msxmX0236）。作者声明他们没有利益冲突。试用注册号 不适用。