Work

Dibutyl phthalate exposure suppresses Wnt/β-catenin pathway and induces oxidative damage in placenta

Year: 2025
Type: article
Abstract: Currently, the literature on mechanistic studies of the toxicity of phthalate metabolites on placental development is not only limited but also incomplete. Given this, the core aim of this study was to investigate in depth the potential association between exposure to dibutyl phthalate (DBP) during pregnancy and placental development. A series of experiments were conducted to achieve this goal. Firstly, the human placenta was carefully examined; meanwhile, the rat animal model and HTR8/svn cell model were constructed. Using relevant experimental techniques, we examined the expression of PLGF and VEGF, which are key factors in placental development, and the expression of Wnt/β-catenin pathway-related factors and oxidative stress factors. The results showed that DBP exposure down-regulated the expression of SATB1, β-catenin, PLGF, and VEGF, and up-regulated the expression of GSK-3β and APC, which inhibited the Wnt/β-catenin pathway in human placenta, rat placenta and HTR8/svn cells. In addition, DBP exposure increased superoxide dismutase (SOD) activity, increased malondialdehyde (MDA) and glutathione (GSH) levels, and decreased catalase (CAT) activity, which ultimately led to oxidative damage to placental tissues and cells. Animal experiments further confirmed that DBP adversely affected the normal development of the rat placenta, resulting in fetal weight loss, shortened length, and inhibited placental cell proliferation. In the HTR8/svneo cell assay, the use of specific agonists and inhibitors to regulate the Wnt/β-catenin pathway could attenuate or exacerbate the toxicity and oxidative damage produced by DBP on HTR8/svneo cells. In conclusion, DBP exposure during pregnancy adversely affects the normal development of the placenta by inhibiting the Wnt/β-catenin pathway and increasing the oxidative damage to the placenta.
Language: English
Open Access status: gold
Estimated APC paid: $3,650
OpenAlex ID: W4410782850
FWCI: 1.591
Cites: 56
Cited by: 4
Related to: 10