Multiomics profiling uncovers curdione-induced reproductive toxicity in HTR-8/SVneo cells
Qibin Wu,
Mengting Chen,
Yifan Lin,
Jian Zhang,
Xinyue Gao,
Yajiao Wu,
Caijin Wu,
Jiaxin Wen,
Jiaqi Li,
Chutao Li,
Wenqiang Bao,
Dongcheng Zhang,
Meijin Zheng,
An Zhu
Affiliations
Qibin Wu
Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, China
Mengting Chen
Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, 350108, China
Yifan Lin
Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, 350108, China
Jian Zhang
Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, 350108, China
Xinyue Gao
Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, 350108, China
Yajiao Wu
Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, 350108, China
Caijin Wu
Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, China
Jiaxin Wen
Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, 350108, China
Jiaqi Li
Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, 350108, China
Chutao Li
Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, 350108, China
Wenqiang Bao
Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, 350108, China
Dongcheng Zhang
Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, 350108, China
Meijin Zheng
Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, China; Corresponding author. Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, China.
An Zhu
Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics & Gynecology and Pediatrics, Fujian Medical University, Fuzhou 350001, China; Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, 350108, China; Corresponding author. Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, Fuzhou, 350108, China.
The assessment of medication toxicity and safety is pivotal during pregnancy. Curdione, a sesquiterpene compound extracted from Curcumae Radix, displays beneficial properties in terms of anti-inflammatory, tumor growth suppression, and anti-coagulative effects. However, its reproductive toxicity and precise mechanism remain unclear. This study aims to explore the mechanism of curdione-induced toxicity damage in HTR-8/SVneo cells through the epigenetics, proteomics, and metabolomics, and experimental verification. The results showed that curdione elicited alterations in m6A modification, gene expression, protein levels, and cellular metabolism of HTR-8/SVneo cells. Additionally, curdione induces oxidative stress, mitochondrial and DNA damage, while also downregulating the expression of Wnt6, β-catenin, ZO-1, and CLDN1 proteins. Curdione has the potential to modulate oxidative stress, mitochondrial dysfunction, and disruption of tight junctions via the Wnt/β-catenin signaling pathway, which contributes to cellular damage in HTR-8/SVneo cells.
