Department of Physiology, Basic Medical College, Nanchang University, Nanchang, Jiangxi, 330006, PR China; Nursing School of Jiujiang University, Jiujiang, Jiangxi, 332000, PR China.
Department of Physiology, Basic Medical College, Nanchang University, Nanchang, Jiangxi, 330006, PR China.
Food Chem Toxicol. 2023 Mar;173:113640. doi: 10.1016/j.fct.2023.113640. Epub 2023 Jan 29.
Glyphosate-based herbicides (GBHs) are the most widely used agrochemicals worldwide, increasing the risk of their occurrence in the environment. This study aimed to explore effects and mechanisms of GBH exposure on placental development in vivo during pregnancy in mice. Pregnant mice received GBH by gavage at 0, 5, and 50 mg⋅kg⋅day doses from gestational day (GD) 1 to GD 13 and were sacrificed on GD 13 or GD19. Our data indicated that GBH administration significantly increased the number of resorbed fetuses, reduced the weight of fetuses and placentas, and inhibited placental growth, as evident from decreased placental total area and spongiotrophoblast area on GD 19. GBH treatment also inhibited proliferation and induced apoptosis of placenta via upregulation of Bax, cleaved caspase-3 and -12 expression, and downregulation of B cell lymphoma (Bcl)-2 expression. Further study showed that GBH exposure significantly increased expression levels of glucose-regulated protein 78 (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), and C/EBP homologous protein (CHOP) mRNAs and proteins and triggered oxidative stress in placenta on GD 13 and GD 19. In conclusion, our findings suggest that maternal exposure to GBH can impair placental development through the endoplasmic reticulum stress-mediated activation of GRP78/PERK/CHOP signaling pathway in mice.
草甘膦基除草剂（GBHs）是全球应用最广泛的农用化学品，增加了其在环境中出现的风险。本研究旨在探讨 GBH 暴露对怀孕小鼠体内胎盘发育的影响和作用机制。从妊娠第 1 天（GD1）到第 13 天（GD13），怀孕小鼠通过灌胃接受 0、5 和 50mg⋅kg⋅day 剂量的 GBH，并在 GD13 或 GD19 处死。我们的数据表明，GBH 给药显著增加了吸收胎的数量，降低了胎儿和胎盘的重量，并抑制了胎盘生长，这表现在 GD19 时胎盘总面积和海绵滋养层面积减少。GBH 处理还通过上调 Bax、cleaved caspase-3 和 -12 的表达和下调 B 细胞淋巴瘤（Bcl）-2 的表达，抑制胎盘增殖并诱导其凋亡。进一步的研究表明，GBH 暴露在 GD13 和 GD19 时显著增加了葡萄糖调节蛋白 78（GRP78）、蛋白激酶 RNA 样内质网激酶（PERK）和 C/EBP 同源蛋白（CHOP）mRNA 和蛋白质的表达水平，并引发了胎盘的氧化应激。总之，我们的研究结果表明，母体暴露于草甘膦基除草剂可能通过内质网应激介导的 GRP78/PERK/CHOP 信号通路的激活损害小鼠胎盘的发育。
