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. 2020 Feb 8;21(3):1135. doi: 10.3390/ijms21031135

Table 2.

Effects of melatonin on assisted reproductive technology under in vitro conditions. COC: cumulus oocyte complex; IVM: in vitro maturation; M II: metaphase II; ROS: reactive oxygen species; MT1, MT2: melatonin membrane receptors; BMP: bone morphogenic protein; PTX3: pentraxin-3; HAS2: hyaluronan synthase 2; EGFR: epidermal growth factor receptors; GSH: glutathione; ATP: adenosine triphosphate; GDF: growth differentiation factor; SOD: superoxide dismutase; GPX: glutathione peroxidase; Bcl-2: B-cell lymphoma-2; GSX: reduced glutathione; OCT4: octamer-binding transcription factor 4; H2AX: histone H2 family member X; H3K4me: methylation of lysine4 on histone H3; H4K27me: methylation of lysine27 on histone H3; CAT: catalase; HSP: heat shock protein; MTNR1A: melatonin receptor 1A; MT: melatonin receptor; 4P-PDOT: 4-phenyl-2-propionamidotetralin; BimEL: Bcl-2 interacting mediator of cell death extra-long; ERK: extracellular signal-regulated kinase; H3K9: histone H3 lysine 9.

Animal Design Melatonin Treatment Result Year Author/Reference
mouse vitro COCs 10−6 M Cumulus expansion, M-Ⅱ ↑
ROS, Acetyla on level of H4k12 ↓
2017 Keshavarzi Somayeh [51]
mouse vitro, IVM, implantation 10−7 M blastocyst rate, hatching blastocyst rate and blastocyst cell number ↑
pregnancy rate and birth rate↑, (ROS) production and cellular apoptosis ↓
2017 Tian Xiuzhi [69]
sheep vitro, IVM 10−7 M rates of nuclear maturation, cumulus cells expansion, cleavage, and blastocyst ↑
MT1 and MT2 were expressed in oocytes, cumulus cells, and granulosa cells
BMP15, PTX3, HAS2, EGFR ↑, cAMP level ↓, cGMP ↑
2017 Tian Xiuzhi [65]
bovine vitro, IVM 10−9 M ROS↓, GSH↑,mitochondrial normal distribution increase ATP level
upregulated ATPase 6, BMP-15, GDF-9, SOD-1, Gpx-4, and Bcl-2
downregulated apoptotic gene expression of caspase-3.
2017 Yang Minghui [68]
porcine vitro IVM COCs 10−7, 10−6, 10−5 M oocyte quality, embryo development ↑
ROS generation, apoptosis, and DNA damage ↓, GSX, OCT4, H2AX
2018 Lin Tao [52]
bovine vitro, IVM 10−9 M G1 blastocyst ↑, cell number ↑,
apoptotic cell ↓
glutathione content, mitochondrial membrane potential ↑
antioxidant gene (SOD2) heat shock protein (HSPB1) ↑
2018 Marques TC [53]
porcine vitro prolonged culture 10−3 M blastocyst rate↑ methylation at H3K4me2 and H3K27me2 ↓
imprinted gene NNAT ↓
2018 Nie Junyu [71]
bovine vitro, IVM 10−9 M blastocyst, total cell number ↑, apoptotic cell ↓
ROS ↓, GSH ↑ caspase-3 ↓, BCL-2, XIAP, CAT, HSP70 ↑
2018 Pang Yunwei [66]
Goat vitro, IVM 10−9 M, 10−12 M M-II stage, blastocyst ↑, GSH ↑, MTNR1A in cumulus cell and oocytes
DNA methyltransferases (DNMTs) global DNA methylation ↓
2018 Saeedabadi Saghar [63]
mouse vitro, IVM 10 μM fertilization rate ↑
hyaluronan synthase-2 (HAS2) and Progesterone receptor (PGR) ↑
2018 Ezzati Maryam [70]
porcine vitro COCs 10−9 M blastocyst, cell number, cumulus expansion ↑, apoptosis ↓
MT2 was expressed in both oocytes and cumulus cells
M effects were abolished when either luzindole or 4P-PDOT (MT antagonist)
2018 Lee Sanghoon [62]
porcine vitro COCs 10−9 M pro-apoptotic protein BimEL, ERK-mediated phosphorylation
M only promoted the ubiquitination of phosphorylated BimEL
M action was independent of its receptor and its antioxidant properties
2018 Wang Yingzheng [67]
bovine vitro cloned embryo 10−9 M cloned embryo development ↑
oxidative stress, apoptosis, mitochondria, chromosome alignment
epigenetic modifications, H3K9 acetylation ↑, H3K9 methylation ↓
2019 An Quanli [56]