3-Nitropropionic acid induces ovarian oxidative stress and impairs follicle in mouse

• Published in: PloS one Vol. 9; no. 2; p. e86589
• Main Authors: Zhang, Jia-Qing, Shen, Ming, Zhu, Cheng-Cheng, Yu, Feng-Xiang, Liu, Ze-Qun, Ally, Nazim, Sun, Shao-Chen, Li, Kui, Liu, Hong-Lin
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05-02-2014; Public Library of Science (PLoS)
• Subjects: 3-Nitropropionic acid; Acids; Animal sciences; Animal tissues; Animals; Antihypertensive Agents - pharmacology; Antioxidants; Apoptosis; Apoptosis - drug effects; Bcl-2 protein; bcl-2-Associated X Protein - metabolism; Biology; Brain; Brain research; Catalase; Chemistry; Embryogenesis; Embryonic development; Embryonic growth stage; Embryos; Enzymes; Female; Follicles; Follicular Atresia - drug effects; Free radicals; Gene expression; Genetics; Glutathione; Glutathione peroxidase; Granulosa cells; Granulosa Cells - metabolism; Granulosa Cells - pathology; Health care; Health risks; In vitro fertilization; Ionizing radiation; Kidneys; Laboratory animals; Liver; Mammals; Medicine; Mice; Mice, Inbred ICR; Mitochondria; Mitochondrial DNA; Nitro Compounds - pharmacology; Oocytes; Ovaries; Oxidative stress; Oxidative Stress - drug effects; Oxidoreductases - metabolism; Oxygen; Peroxidase; Propionates - pharmacology; Reactive oxygen species; Reactive Oxygen Species - metabolism; Reproductive health; Reproductive system; Rodents; Signal transduction; Spleen; Superoxide dismutase; Superoxides; Toxicology; Weight reduction; Zoology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0086589

Oxidative stress induces many serious reproductive diseases in female mammals and thus poses a serious threat to reproductive health. However, the relationship between reactive oxygen species (ROS)-induced oxidative stress and follicular development, oocyte and embryo quality is not clear. The aim of this study was to investigate the effect of ovarian oxidative stress on the health of follicle and oocyte development. Female ICR mice were dosed with 3-nitropropionic acid (3-NPA) at three different concentrations (6.25, 12.5 and 25 mg/kg) and saline (control) via continuous intraperitoneal injection for 7 days. The treatment with 12.5 mg/kg reduced the weight of mouse ovaries, and significantly increased ROS levels and the activities of antioxidant enzymes--total superoxide dismutase (T-SOD), glutathione peroxidase (GPx) and catalase (CAT)--in granulosa cells and ovarian tissues, but not in other tissues (brain, liver, kidney and spleen). The same treatment significantly increased the percentage of atretic large follicles, and reduced the number of large follicles, the number of ovulated oocytes, and the capacity for early embryonic development compared with controls. It also significantly decreased the ratio of Bcl-2 to Bax, while causing an increase in the mRNA expression of (SOD2, CAT and GP X) and ROS levels in granulosa cells. Collectively, these data indicate that 3-NPA induces granulosa cell apoptosis, large follicle atresia, and an increase of ROS levels in the ovary. Therefore, we have established an in vivo model of ovarian oxidative stress for studying the mechanism of resulting damage induced by free radicals and for the screening of novel antioxidants.