Maternal exposure to a glyphosate-based herbicide impairs placental development through endoplasmic reticulum stress in mice. (March 2023)

• Record Type: Journal Article
• Authors: Liu, Mengling; Lu, Siying; Yang, Chuanzhen; Zhang, Dalei; Zhu, Jun; Yin, Jiting; Zhao, Hongru; Yang, Bei; Kuang, Haibin
• Is Part Of: Food and chemical toxicology. Volume 173(2023)
• Publication Date: 2023-03
• Subjects: Glyphosate-based herbicides -- Placenta -- Apoptosis -- Endoplasmic reticulum stress -- Pregnancy; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2023.113640
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: 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 −1 ⋅day −1 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. Graphical abstract: Image 1 Highlights: Maternal exposure to GBH increased the numbers of resorbed fetus. GBH inhibited the placental development. GBH induced placental apoptosis by endoplasmic reticulum stress. GRP78/PERK/CHOP pathway was involved in GBH-induced placental impairment.