Long-Term Moderate Oxidative Stress Decreased Ovarian Reproductive Function by Reducing Follicle Quality and Progesterone Production.

Long-Term Moderate Oxidative Stress Decreased Ovarian Reproductive Function by Reducing Follicle Quality and Progesterone Production.
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长期中度氧化应激会降低卵泡质量和黄体酮生成,从而降低卵巢生殖功能

DOI:
10.1371/journal.pone.0162194
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发表时间:
2016
期刊:
影响因子:
3.7
通讯作者:
Wang S
Wang S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Shi L;Zhang J;Lai Z;Tian Y;Fang L;Wu M;Xiong J;Qin X;Luo A;Wang S

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卵巢衰老是一个长期而复杂的过程,与卵泡数量和质量的下降有关。活性氧(ROS)在卵巢衰老和卵巢衰老相关疾病中的损伤作用受到的关注相对较少。因此,我们评估了长期(环境保护局定义为至少持续30天)适度臭氧吸入诱导的氧化应激是否会降低卵巢储备,降低卵巢功能并诱导卵巢衰老相关疾病。氧化应激标志物和抗氧化酶的表达被用来确定氧化应激的程度。电镜观察卵巢细胞超微结构的变化。通过测量多个参数来评估卵巢储备,例如原始卵泡池的大小和抗苗勒管激素(AMH)表达。观察发情周期、激素水平和生育状况,以评估卵巢功能。为了研究卵巢衰老相关的疾病,我们利用小鼠的骨密度和心血管超声检查。卵巢细胞中的氧化代谢产物,如8-羟基-2 ′-脱氧鸟苷(8-OHdG)、4-羟基壬烯醛(4-HNE)和硝基酪氨酸(NTY)的水平在氧化应激增加时显著增加。超微结构分析表明,与对照组相比,臭氧暴露小鼠的颗粒细胞中的脂滴形成和线粒体与受损膜的比例显着增加。臭氧暴露没有改变原始卵泡池的大小或抗苗勒管激素(AMH)的表达。雌激素浓度保持正常;然而,孕酮和睾酮水平下降。暴露于臭氧吸入的小鼠表现出生育力和繁殖力的大幅下降。骨密度或心血管超声检查显示无差异。这些发现表明,长期中度氧化损伤引起的女性生殖功能下降可能是由于卵泡质量和孕酮产量下降。
Ovarian aging is a long-term and complex process associated with a decrease in follicular quantity and quality. The damaging effects of reactive oxygen species (ROS) in ovarian aging and ovarian aging-associated disorders have received relatively little attention. Thus, we assessed if the oxidative stress induced by long-term (defined by the Environmental Protection Agency as at least 30 days in duration) moderate ozone inhalation reduced ovarian reserves, decreased ovarian function and induced ovarian aging-associated disorders. The expression of oxidative stress markers and antioxidant enzymes was used to determine the degree of oxidative stress. Ultrastructural changes in ovarian cells were examined via electron microscopy. The ovarian reserve was assessed by measuring multiple parameters, such as the size of the primordial follicle pool and anti-Müllerian hormone (AMH) expression. The estrous cycle, hormone levels and fertility status were investigated to assess ovarian function. To investigate ovarian aging-associated disorders, we utilized bone density and cardiovascular ultrasonography in mice. The levels of oxidized metabolites, such as 8-hydroxy-2´-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE) and nitrotyrosine (NTY), significantly increased in ovarian cells in response to increased oxidative stress. The ultrastructural analysis indicated that lipid droplet formation and the proportion of mitochondria with damaged membranes in granulosa cells were markedly increased in ozone-exposed mice when compared with the control group. Ozone exposure did not change the size of the primordial follicle pool or anti-Müllerian hormone (AMH) expression. The estrogen concentration remained normal; however, progesterone and testosterone levels decreased. The mice exposed to ozone inhalation exhibited a substantial decrease in fertility and fecundity. No differences were revealed by the bone density or cardiovascular ultrasounds. These findings suggest that the decreased female reproductive function caused by long-term moderate oxidative damage may be due to a decrease in follicle quality and progesterone production.
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