Norflurazon, an inhibitor of carotenoid synthesis, is a pre-emergent herbicide that prevents growth of weeds. The norflurazon is known to hamper embryo development in non-mammals. However, specific toxic effects of norflurazon on mammalian maternal and fetal cells have not been elucidated. Thus, the hypothesis of this study is that norflurazon may influence the toxic effects between maternal and fetal cells during early pregnancy in pigs. We aimed to examine the toxic effects of norflurazon in porcine trophectoderm (Tr) and uterine luminal epithelium (LE) cells. Norflurazon, administered at 0, 20, 50 or 100 μM for 48 h was used to determine its effects on cell proliferation and cell-cycle arrest. For both uterine LE and Tr cell lines, norflurazone caused mitochondrial dysfunction by inhibiting mitochondrial respiration and ATP production, and down-regulated expression of mRNAs of mitochondrial complex genes. Norflurazon increased cell death by increasing intracellular calcium and regulating PI3K and MAPK cell signaling pathways, as well as endoplasmic reticulum (ER) stress, ER-mitochondrial contact, and autophagy-related target proteins. Norflurazone also inhibited expression of genes required for implantation of blastocysts, including , , and . These findings indicate that norflurazon may induce implantation failure in pigs and other mammals through adverse effects on both Tr and uterine LE cells.

中文翻译：

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Norflurazon 导致细胞死亡并抑制猪滋养外胚层和子宫腔上皮细胞中与着床相关的基因

Norflurazon 是一种类胡萝卜素合成抑制剂，是一种芽前除草剂，可防止杂草生长。已知诺氟拉酮会阻碍非哺乳动物的胚胎发育。然而，诺氟拉松对哺乳动物母体和胎儿细胞的具体毒性作用尚未阐明。因此，本研究的假设是，氟磺草酮可能会影响猪妊娠早期母体和胎儿细胞之间的毒性作用。我们的目的是检查诺氟拉松对猪滋养外胚层 (Tr) 和子宫腔上皮 (LE) 细胞的毒性作用。 Norflurazon 以 0、20、50 或 100 μM 给药 48 小时，用于确定其对细胞增殖和细胞周期停滞的影响。对于子宫 LE 和 Tr 细胞系，去甲氟拉酮通过抑制线粒体呼吸和 ATP 产生以及下调线粒体复合物基因 mRNA 的表达而导致线粒体功能障碍。 Norflurazon 通过增加细胞内钙和调节 PI3K 和 MAPK 细胞信号通路以及内质网 (ER) 应激、ER-线粒体接触和自噬相关靶蛋白来增加细胞死亡。诺氟拉酮还抑制胚泡植入所需基因的表达，包括 、 和 。这些发现表明，诺氟拉松可能通过对 Tr 和子宫 LE 细胞产生不利影响，导致猪和其他哺乳动物着床失败。