title: Melatonin inhibits paraquat-induced cell death in bovine preimplantation embryos.
abstract: Preimplantation embryos are sensitive to oxidative stress-induced damage that can be caused by reactive oxygen species (ROS) originating from normal embryonic metabolism and/or the external surroundings. Paraquat (PQ), a commonly used pesticide and potent ROS generator, can induce embryotoxicity. The present study aimed to investigate the effects of melatonin on PQ-induced damage during embryonic development in bovine preimplantation embryos. PQ treatment significantly reduced the ability of bovine embryos to develop to the blastocyst stage, and the addition of melatonin markedly reversed the developmental failure caused by PQ (20.9% versus 14.3%). Apoptotic assay showed that melatonin pretreatment did not change the total cell number in blastocysts, but the incidence of apoptotic nuclei and the release of cytochrome c were significantly decreased. Using real-time quantitative polymerase chain reaction analysis, we found that melatonin pre-incubation significantly altered the expression levels of genes associated with redox signaling, particularly by attenuating the transcript level of Txnip and reinforcing the expression of Trx. Furthermore, melatonin pretreatment significantly reduced the expression of the pro-apoptotic caspase-3 and Bax, while the expression of the anti-apoptotic Bcl-2 and XIAP was unaffected. Western blot analysis showed that melatonin protected bovine embryos from PQ-induced damage in a p38-dependent manner, but extracellular signal-regulated kinase (ERK) and c-JUN N-terminal kinase (JNK) did not appear to be involved. Together, these results identify an underlying mechanism by which melatonin enhances the developmental potential of bovine preimplantation embryos under oxidative stress conditions.
authors.affiliation: Embryo Biotechnology and Reproduction Laboratory, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Yun-Wei
authors.initials: YW
authors.lastname: Pang
authors.affiliation: Embryo Biotechnology and Reproduction Laboratory, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Ye-Qing
authors.initials: YQ
authors.lastname: Sun
authors.affiliation: Embryo Biotechnology and Reproduction Laboratory, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Wei-Jun
authors.initials: WJ
authors.lastname: Sun
authors.affiliation: Embryo Biotechnology and Reproduction Laboratory, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Du
authors.affiliation: Embryo Biotechnology and Reproduction Laboratory, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Hai-Sheng
authors.initials: HS
authors.lastname: Hao
authors.affiliation: Embryo Biotechnology and Reproduction Laboratory, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Shan-Jiang
authors.initials: SJ
authors.lastname: Zhao
authors.affiliation: Embryo Biotechnology and Reproduction Laboratory, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China.
authors.forename: Hua-Bin
authors.initials: HB
authors.lastname: Zhu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001755:Blastocyst / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002417:Cattle; D005260:Female; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008550:Melatonin / Q000494:pharmacology*; D010269:Paraquat / Q000009:adverse effects* / Q000494:pharmacology; D010575:Pesticides / Q000009:adverse effects* / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
chemical_list: D010575:Pesticides; D019253:Proto-Oncogene Proteins c-bcl-2; D051636:X-Linked Inhibitor of Apoptosis Protein; D053148:Caspase 3; D008550:Melatonin; D010269:Paraquat
keywords: apoptosis; embryo; melatonin; oxidative damage; paraquat