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作者

Xiao Gu, Haixia Liu, Wei Luo, Xietong Wang, Hongying Wang, Lei Li

作者单位

Key Laboratory of Birth Regulation and Control Technology of National Health and Family Planning Commission of China, Maternal Child Health Hospital of Shandong Province, Jinan, China. Electronic address: wxt65@vip.16 Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China. ⁴ Department of Obstetrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan 250021, Shandong, China Department of Obstetrics and Gynecology, Liao Cheng People's Hospital, 67 Dongchang West Road, Liaocheng 252000, Shandong, China com. ⁵ Department of Obstetrics and Gynecology, Liao Cheng People's Hospital, 67 Dongchang West Road, Liaocheng 252000, Shandong, China. Electronic address: hongyingwang6@16 com. ⁶ Department of Obstetrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan 250021, Shandong, China. Electronic address: lilei@sdfmu.edu.cn. Affiliations ¹ Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China China Shandong Key Laboratory of Reproductive Medicine, Jinan, Shandong, China. ² Department of Obstetrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan 250021, Shandong, China. ³ Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China

刊名

Reproductive toxicology (Elmsford, N.Y.)

年份

2022

ISSN

1873-1708

关键词

DEHP Lipid metabolism Placenta Trophoblast cAMP/PKA miR-155-5p

摘要

Di-2-ethylhexyl phthalate has been proven to boost miR-155-5p level in trophoblasts, but how DEHP-induced miR-155-5p regulates trophoblastic functions is unclear. For in vivo experiments, DEHP was administered to pregnant Sprague-Dawley rats at various dosages. After birth, the development of rat fetuses was evaluated. The morphology of the placentae was evaluated using HE staining. miR-155-5p level in placentae was measured utilizing RT-qPCR. Placental cAMP/PKA pathway activation and lipid me...更多

Di-2-ethylhexyl phthalate has been proven to boost miR-155-5p level in trophoblasts, but how DEHP-induced miR-155-5p regulates trophoblastic functions is unclear. For in vivo experiments, DEHP was administered to pregnant Sprague-Dawley rats at various dosages. After birth, the development of rat fetuses was evaluated. The morphology of the placentae was evaluated using HE staining. miR-155-5p level in placentae was measured utilizing RT-qPCR. Placental cAMP/PKA pathway activation and lipid metabolism levels were assessed using WB, RT-qPCR, and ELISA. For in vitro experiments, DEHP, miR-155-5p inhibitor, or cAMP/PKA inhibitor were applied to treat HTR-8/Svneo cells. Cell viability and functions were investigated utilizing WB, RT-qPCR, CCK-8, transwell assay, plate colony formation assay, and flow cytometry. Besides, the cAMP/PKA pathway activation and lipid metabolism levels in HTR-8/Svneo cells were detected via ELISA, WB, and RT-qPCR. DEHP resulted in fetal malformations and abnormal placental histopathology. DEHP also promoted placental miR-155-5p expression, the cAMP/PKA inactivation, and lipid metabolism in placentae. miR-155-5p knockdown abrogated DEHP-induced proliferative, migrative, and invasive inhibition in HTR-8/Svneo cells. Moreover, miR-155-5p downregulation abolished DEHP-induced inactivation of the cAMP/PKA pathway and enhanced lipid metabolism. Additionally, DEHP-induced miR-155-5p facilitated lipid metabolism by inhibiting the cAMP/PKA signaling pathway in HTR-8/Svneo cells. The current study reveals that miR-155-5p plays an indispensable role in DEHP-induced trophoblastic toxicity by promoting lipid metabolism via inhibiting the cAMP/PKA signaling pathway, indicating miR-155-5p might be a promising therapeutic target for DEHP exposure during pregnancy.收起

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