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  3. Melatonin mediates the BMP4/MAPK signaling pathway to alleviate zearalenone-induced abnormal embryonic development in mice

Melatonin mediates the BMP4/MAPK signaling pathway to alleviate zearalenone-induced abnormal embryonic development in mice

  • Ecotoxicol Environ Saf. 2025 Apr 1:294:118068. doi: 10.1016/j.ecoenv.2025.118068.
Mengyao Wang 1,  Zhixin Pu 1,  Jing Zhang 1,  Peiwen Wang 1,  Yaxin Chen 1,  Yating Zhu 1,  Hongzhen Ruan 1,  Dongmei Ji 2,  Weiwei Zou 2,  Huiru Cheng 1,  Zhiming Ding 3,  Yunxia Cao 4,  Yajing Liu 5,  Dan Liang 6
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei, Anhui 230032, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, Hefei, Anhui 230032, China.
  • 2 Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China; Engineering Research Center of Biopreservation and Artifical Organs, Ministry of Education, Hefei, Anhui 230032, China; Anhui Province Key Laboratory of Reproductive Health and Genetics, Hefei, Anhui 230032, China.
  • 3 Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei, Anhui 230032, China; Biopreservation and Artificial Organs, Anhui Provincial Engineering Research Center, Anhui Medical University, Hefei, Anhui 230032, China.
  • 4 Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei, Anhui 230032, China; Anhui Provincial Institute of Translational Medicine, Hefei, Anhui 230032, China. Electronic address: caoyunxia6@126.com.
  • 5 Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei, Anhui 230032, China; Anhui Provincial Institute of Translational Medicine, Hefei, Anhui 230032, China. Electronic address: yjl@ustc.edu.cn.
  • 6 Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, China; NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract (Anhui Medical University), Hefei, Anhui 230032, China; Key Laboratory of Population Health Across Life Cycle (Anhui Medical University), Ministry of Education of the People's Republic of China, Hefei, Anhui 230032, China; Engineering Research Center of Biopreservation and Artifical Organs, Ministry of Education, Hefei, Anhui 230032, China. Electronic address: ahmuxl@sina.com.
PMID: 40120487 DOI: 10.1016/j.ecoenv.2025.118068
Abstract

Zearalenone (ZEA) is a common mycotoxin found in crops that poses a threat to human health, particularly the female reproductive system. Here, we show that exposing mouse zygotes to ZEA in vitro significantly impairs embryo development, leading to embryo arrest. Remarkably, treatment of ZEA-exposed mouse embryos with melatonin significantly improved the blastocyst rates from approximately 40 % to nearly 80 %. Furthermore, melatonin effectively mitigates the harmful effects of ZEA exposure by reducing Reactive Oxygen Species (ROS) levels, preventing mitochondrial dysfunction, and decreasing cell Apoptosis. Following embryo transplantation, the birth rate of offspring increased markedly from 7.2 % to 23.62 %. Further research revealed that the abnormal elevation of bone morphogenetic protein 4 (BMP4) signaling induced by ZEA exposure, coupled with the inhibition of the downstream mitogen-activated protein kinase (MAPK) signaling pathway, contributes to developmental blockade in ZEA-exposed mouse embryos. Melatonin rescued ZEA-induced defects in mouse embryo development by inhibiting BMP4 signaling and regulating the MAPK pathway. Moreover, the Bmp4 inhibitor Noggin or its receptor inhibitor DMH-1 could also effectively ameliorate the ZEA-induced impairment of embryo development. Taken together, these findings underscore the potential of melatonin as a therapeutic intervention for addressing the adverse effects of ZEA exposure on mouse embryos.

Keywords

Bone morphogenetic protein 4; Embryo development; Melatonin; Mitogen-activated protein kinase; Zearalenone.

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