Effect of oxidative stress during repeated ovulation on the structure and functions of the ovary, oocytes, and their mitochondria
Effect of oxidative stress during repeated ovulation on the structure and functions of the ovary, oocytes, and their mitochondria
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DOI：
10.1016/j.freeradbiomed.2010.05.025
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发表时间：
2010-08-15
影响因子：
7.4
通讯作者：
Inoue, Masayasu
中科院分区：
文献类型：
--
作者：
Miyamoto, Kaori;Sato, Eisuke F.;Inoue, Masayasu
我们以前报道过，卵巢中产生的超氧化物诱导颗粒细胞凋亡，破坏卵泡壁，从而支持啮齿动物排卵，并建议氧化应激是卵巢衰老的机制之一。为了验证这一假设，我们成功地诱导排卵反复在小鼠中依次给予孕马血清促性腺激素，人绒毛膜促性腺激素，前列腺素F2 α。动力学分析表明，排卵的卵母细胞的数量显着减少，与伴随的线粒体转录因子A和核呼吸因子1的基因表达的减少，并在卵母细胞中有异常分布的线粒体。重复排卵使卵母细胞线粒体DNA含量减少，8-羟基脱氧鸟苷含量增加。体外受精卵母细胞的细胞培养分析表明，重复排卵显著抑制了卵母细胞从两个细胞到囊胚的成熟。所有这些事件引起的重复排卵抑制口服左旋肉碱。这些结果表明，与排卵相关的氧化应激是卵巢衰老机制的基础，左旋肉碱可能对不孕症患者具有治疗潜力，并增加非整倍体的发生率，并抑制在高龄生育中经常观察到的受精卵成熟受损。(C)2010年爱思唯尔公司All rights reserved.
We previously reported that superoxide generated in the ovary induces apoptosis of granulosa cells to break down follicular walls, thereby supporting ovulation in rodents, and suggested that oxidative stress underlies the mechanism of ovarian aging. To test this hypothesis, we successfully induced ovulation repeatedly in mice by sequentially administrating pregnant mare serum gonadotropin, human chorionic gonadotropin, and prostaglandin F2 alpha. Kinetic analysis revealed that the number of ovulated oocytes decreased significantly with repeated cycles of ovulation with a concomitant decrease in the gene expression of mitochondrial transcription factor A and nuclear respiratory factor 1 and an increase in oocytes having abnormally distributed mitochondria. Repeated ovulation decreased the amounts of mitochondrial DNA and increased 8-hydroxydeoxyguanosine in oocytes. Cell culture analysis of the in vivo fertilized oocytes revealed that their maturation from two cells to blastocyst was inhibited significantly by repeated ovulation. All these events induced by repeated ovulation were suppressed by oral administration of L-carnitine. These results suggest that oxidative stress associated with ovulation underlies the mechanism of ovarian aging and that L-carnitine may have therapeutic potential in patients with infertility and increased incidence of aneuploidy and to suppress impaired maturation of zygotes frequently observed in childbearing at an advanced age. (C) 2010 Elsevier Inc. All rights reserved.