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• Juglone exposure led to the defects of mouse early embryo development. • Juglone exposure disturbed mitochondrial function in mouse early embryo. • Juglone exposure produced abnormal epigenetic modifications in early embryo. • Vitamin C eliminated the excessive ROS induced by juglone exposure. • Vitamin C reduced DNA damage and apoptosis caused by juglone exposure. Juglone, a naphthoquinone isolated from many species of the Juglandaceae (walnut) family, has been used in traditional Chinese medicine for centuries for its various pharmacological effects. Our previous research found its toxic effects on oocytes maturation. But we still know a little about its toxic effects on embryo development. Here, we used mouse embryo as a model to explore the effects of juglone on early mammalian embryo development. Exposure to juglone significantly decreased the development rate in early mouse embryos in vitro. Moreover, juglone exposure led to developmental arrest by disturbing mitochondrial function, producing abnormal epigenetic modifications, inducing high levels of oxidative stress and DNA damage, and increasing the rate of embryonic cell apoptosis. However, vitamin C (VC) ameliorated the toxic effects of juglone to a certain extent. Overall, juglone has a toxic effect on early embryo development through the generation of ROS and apoptosis. But VC was able to protect against these juglone-induced defects. These results not only give a new perspective on juglone's pharmacological effects on early mammalian embryo development, but also provide ideas for the better application of this agent in traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

Heavy metal cadmium (Cd) is a widespread environmental contaminant with a potential toxicity that might adversely influence the health of experimental animals and humans. It has been known that Cd might accumulate in vertebrates for many years and thus leads to the hepatic and renal toxicity. Additionally, Cd concentration in the ovary increases with age and is highly related to the reproductive hazard. However, the underlying mechanisms regarding how Cd affects the female reproductive system especially the oocyte quality have not yet fully defined. Here, we reported that Cd exposure led to the defective nuclear maturation of oocytes via the impairment of cytoskeleton assembly, displaying the aberrant spindle organization, chromosome alignment and actin polymerization. In the meantime, Cd exposure caused the impaired cytoplasmic maturation by showing the disrupted dynamics of mitochondrial integrity and cortical granules, and thereby resulting in the compromised sperm binding ability and fertilization capacity of oocytes. More importantly, we found that glutathione (GSH) supplementation was able to recover the meiotic failure induced by Cd exposure through suppressing the excessive ROS level, DNA damage accumulation and apoptotic incidence. Taken together, our findings demonstrate that Cd exposure has the adverse effects on the oocyte meiotic maturation as well as subsequent fertilization, and provide a potential effective strategy to improve the quality of Cd-exposed oocytes. Image 1 • Cd exposure led to the defective nuclear maturation of oocytes via the impairment of cytoskeleton assembly. • Cd exposure caused impaired cytoplasmic maturation of oocytes by disrupting dynamics of mitochondria and cortical granules. • Cd exposure resulted in the compromised sperm binding ability and fertilization capacity of oocytes. • Glutathione supplementation recovered the meiotic failure induced by Cd exposure through eliminating the excessive ROS. [ABSTRACT FROM AUTHOR]

The Cullin9 gene encodes a putative E3 ligase that serves a wide variety of biological functions in mitosis, whereas its roles in meiosis have not yet clearly defined. Here, we report that Cullin9 accumulates on the spindle apparatus and colocalizes with the microtubule fibers during mouse oocyte meiotic maturation. Depletion of Cullin9 by morpholino microinjection results in a remarkably higher rate of disorganized spindles and misaligned chromosomes in oocytes, which is coupled with the impaired kinetochore-microtubule attachments. Resultantly, the incidence of aneuploid eggs significantly increases in Cullin9-depleted oocytes. Moreover, we show that Cullin9 controls Survivin's protein level during meiotic maturation, and thus regulates microtubule stability in oocytes. Thus, our study assigns a new meiotic function to Cullin9 and reveals that it prevents mouse eggs from aneuploidy by regulating microtubule dynamics via Survivin. [ABSTRACT FROM AUTHOR]