Prenatal exposure to triphenyl phosphate activated PPARγ in placental trophoblasts and impaired pregnancy outcomes
2022
Hong, Jiabin | Jiang, Mengzhu | Guo, Lihao | Lin, Juntong | Wang, Yao | Tang, Huanwen | Liu, Xiaoshan
The health risks of triphenyl phosphate (TPhP) have increased since its widespread application. Using placental trophoblast cell line JEG-3, we demonstrated that TPhP could induce endoplasmic reticulum stress (ERS) and cell apoptosis through PPARγ-mediated lipid metabolism. However, the developmental toxicity of TPhP through the placenta is not known. In this study, prenatal TPhP exposure to mice was investigated. Pregnant mice were orally exposed to TPhP (1 and 5 mg/kg) from embryonic day 0 (E0) until delivery. The results showed that TPhP could accumulate in placenta and impair pregnancy outcomes. After exposure, at E18, placental hormone chorionic gonadotrophin and testosterone levels were significantly decreased, but progesterone and estradiol levels were significantly increased, and placental angiogenesis was activated in the low-dose exposure group. While, in the high-dose exposure group, only estradiol levels were significantly increased. Different with the effect on hormone level or angiogenesis, TPhP significantly increased PPARγ and its regulated lipid transport proteins FABP, FATP, and CD36, and induced lipid accumulation in placental trophoblasts of both low- and high-exposure group. RNA-seq analysis of the placenta identified differentially expressed genes that were mainly involved in the ERS and MAPK signaling pathways. Western blot analysis verified that the protein levels related to ERS stress and apoptosis were significantly increased. To further confirm the role of PPARγ in TPhP mediated placental toxicity, pregnant mice were orally exposed to TPhP (1 mg/kg) or TPhP (1 mg/kg) + GW9662 (PPARγ inhibitor, 2 mg/kg) from E0 until delivery. The results showed that GW9662 could ameliorate the effect of TPhP on placental lipid accumulation, ERS and cell apoptosis, suggesting that PPARγ mediated the placental toxicity of TPhP. Overall, our results indicated that prenatal TPhP exposure impaired pregnancy outcomes, at least partly through PPARγ regulated function of trophoblast.
اظهر المزيد [+] اقل [-]الكلمات المفتاحية الخاصة بالمكنز الزراعي (أجروفوك)
المعلومات البيبليوغرافية
تم تزويد هذا السجل من قبل National Agricultural Library