title: Beneficial effects of melatonin on in vitro bovine embryonic development are mediated by melatonin receptor 1.
abstract: In the current study, a fundamental question, that is, the mechanisms related to the beneficial effects of melatonin on mammalian embryonic development, was addressed. To examine the potential beneficial effects of melatonin on bovine embryonic development, different concentrations of melatonin (10(-11), 10(-9), 10(-7), 10(-5), 10(-3) M) were incubated with fertilized embryos. Melatonin in the range of 10(-11) to 10(-5) M significantly promoted embryonic development both in early culture medium (CR1aa +3 mg/mL BSA) and in later culture medium (CR1aa + 6%FBS). The most effective concentrations applied in the current studies were 10(-9) and 10(-7) M. Using quantitative real-time PCR with immunofluorescence and Western blot assays, the expression of melatonin receptor MT1 and MT2 genes was identified in bovine embryos. Further studies indicate that the beneficial effects of melatonin on bovine embryo development were mediated by the MT1 receptor. This is based on the facts that luzindole, a nonselective MT1 and MT2 antagonist, blocked the effect on melatonin-induced embryo development, while 4-P-PDOT, a selective MT2 antagonist, had little effect. Mechanistic explorations uncovered that melatonin application during bovine embryonic development significantly up-regulated the expression of antioxidative (Gpx4, SOD1, bcl-2) and developmentally important genes (SLC2A1, DNMT1A, and DSC2) while down-regulating expression of pro-apoptotic genes (P53, BAX, and Caspase-3). The results obtained from the current studies provide new information regarding the mechanisms by which melatonin promotes bovine embryonic development under both in vitro and in vivo conditions.
authors.affiliation: State Key Laboratory of Animal Nutrition, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetic Improvement in Beijing, College of Animal Science and Technology, China Agricultural University, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: XiuZhi
authors.initials: X
authors.lastname: Tian
authors.forename: Lu
authors.initials: L
authors.lastname: Zhang
authors.forename: Chao
authors.initials: C
authors.lastname: Gao
authors.forename: ChangJiu
authors.initials: C
authors.lastname: He
authors.forename: Yao
authors.initials: Y
authors.lastname: Fu
authors.forename: PengYun
authors.initials: P
authors.lastname: Ji
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: GuoShi
authors.initials: G
authors.lastname: Liu
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000187:drug effects; D002417:Cattle; D047108:Embryonic Development / Q000187:drug effects*; D005979:Glutathione Peroxidase / Q000096:biosynthesis; D008550:Melatonin / Q000494:pharmacology*; D044122:Receptor, Melatonin, MT1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D044123:Receptor, Melatonin, MT2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013482:Superoxide Dismutase / Q000096:biosynthesis; D000072105:Superoxide Dismutase-1; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014363:Tryptamines / Q000494:pharmacology
chemical_list: C114459:4-phenyl-2-propionamidotetraline; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D013764:Tetrahydronaphthalenes; D014363:Tryptamines; C057154:luzindole; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D008550:Melatonin
keywords: bovine; embryo; in vitro culture; melatonin; melatonin membrane receptor 1