Extracellular vesicles and melatonin benefit embryonic develop by regulating reactive oxygen species and 5-methylcytosine

细胞外囊泡和褪黑激素通过调节活性氧和 5-甲基胞嘧啶有益于胚胎发育

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作者:Pengxiang Qu, Shiwei Luo, Yue Du, Yanru Zhang, Xiaojie Song, Xuetao Yuan, Zujie Lin, Yuchen Li, Enqi Liu

Abstract

Embryo culture conditions are crucial as they can affect embryo quality and even offspring. Oviductal extracellular vesicles (EVs) long been considered a major factor influencing interactions between the oviduct and embryos, and thus its absence is associated with inferior embryonic development in in vitro culture. Herein, we demonstrated that melatonin is present in oviduct fluids and oviduct fluid-derived EVs. Addition of either EVs (1.87 × 1011 particles/mL) or melatonin (340 ng/mL) led to a significant downregulation of reactive oxygen species (ROS) and 5-methylcytosine (5-mC), as well as an increase in the blastocyst rate of embryos, which was inhibited by the addition of luzindole-a melatonin receptor agonist. A combination of EVs (1.87 × 1010 particles/mL) and melatonin (at 34.3 pg/mL) led to the same results as well as a significant decrease in the apoptosis index and increase in the inner cell mass (ICM)/trophectoderm (TE) index. These results suggest that an EV-melatonin treatment benefits embryonic development. Our findings provide insights into the role of EVs and melatonin during cell communication and provide new evidence of the communication between embryos and maternal oviduct.

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