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The effects of plasma-derived extracellular vesicles on cumulus expansion and oocyte maturation in mice
Institution:1. Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;2. Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran;3. Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran;4. Women''s Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran;1. Department of Gynecology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, China;2. Department of Dermatology, Shanghai Baoshan Hospital of Integrated Traditional Chinese and Western Medicine, China;3. Department of Medical Imaging, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, China;1. College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, 730070, Gansu, China;2. Gansu Key Laboratory of Animal Generational Physiology and Reproductive Reg-ulation, China;1. Department of Gynecology, Henan Provincial People’s Hospital; People’s Hospital of Zhengzhou University; People’s Hospital of Henan University, Zhengzhou, 450003, Henan, China;2. Department of Gynecology, Zhou kou Central Hospital, Zhoukou 466000, Henan, China;3. Department of Obstetrics and Gynecology, Zhoukou Maternal and Child Health Care, Zhoukou, 466000, Henan, China;1. Department of Theriogenology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran;2. Institute of Pharmacology and Toxicology, University Medical Center, Georg August University, Göttingen, Germany;3. Department of Embryology, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran;1. Laboratorio de Medicina Reproductiva, Universidad Nacional de Rosario, Suipacha 531, C.P: 2000, Rosario, Santa Fe, Argentina;2. Consejo de Investigaciones de la Universidad Nacional de Rosario (CIUNR), Rosario, Santa Fe, Argentina;3. Consejo Nacional de Investigaciones Científicas y Técnicas, CONICET, Rosario, Santa Fe, Argentina
Abstract:Cumulus cell expansion is required for the ovulation of a fertilizable oocyte. Extracellular vesicles (EVs) are bilayer-lipid membrane vesicles that may be found in a variety of bodily fluids and play an important role in biological processes. This study aimed to examine the effects of plasma-derived EVs on cumulus expansion and in vitro maturation (IVM) of the oocyte. EVswere isolated using ultracentrifugation from the plasma of female mice. The morphology and size of EVs were analyzed by transmission electron microscopy (TEM) and dynamic light scattering (DLS). Western blotting allowed us to identify CD63, CD81, CD9, and HSP70 protein markers of EVs; the expression of the genes related to cumulus cell expansion, including hyaluronan synthase 2 (Has2) and prostaglandinendoperoxide synthase 2 (Ptgs2), were assessed using real-time polymerase chain reaction. Plasma-derived EVs labeled with Dil dye were successfully incorporated with cumulus cells during IVM. Plasma-derived EVs significantly induced cumulus expansion and maturation of oocytes. The percentage of oocytes that reached the MII stage was significantly greater in the EVs treatment group compared with other groups. Although treatment with epidermal growth factor (EGF) significantly increased cumulus expansion in cumulus-oocyte complexes (COCs), the impact was less than that seen with plasma-derived EVs. Furthermore, EVs generated from plasma substantially enhanced Has2 and Ptgs2 mRNA expression in the cumulus-oocyte complex. This research indicates that EVs derived from plasma are capable of promoting cumulus expansion and oocyte maturation.
Keywords:Cumulus expansion  Electronic microscopy  Oocyte maturation  Plasma-derived EVs
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