Qian Y, Shao L, Yuan C, Jiang C-Y, Liu J, Gao C, Gao L, Cui Y-G, Jiang S-W, Liu J-Y, Meng Y
State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, the First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Curr Mol Med. 2016;16(3):243-51. doi: 10.2174/1566524016666160225151647.
Ovarian aging has been associated with increased levels of reactive oxygen species and the deficiencies of antioxidant defense. The antioxidant peroxiredoxin 4 (Prdx4), as a member of Prdx protein family, controls cellular oxidative stress by reducing H2O2 levels. In previous studies, we provided evidence that Prdx4 was abundantly expressed in mouse and human ovaries and expression of Prdx4 in matured follicles was higher than that in immatured follicles. Accordingly, we speculated that Prdx4 expression could be associated with follicle development and it may be as a part of the antioxidative mechanism in follicular development. In this study, we demonstrated that Prdx4 was mainly expressed in the granulosa cells of mouse ovaries and the expression levels significantly increased along development of follicles. However, the expression levels of Prdx4 decreased when mice reached the aged stage (18 months old). Likewise a similar pattern that was observed in the mice study was also found in human ovaries where Prdx4 was expressed lower in premenopausal women than young women. Subsequent in vitro experiments indicated that Prdx4 mRNA and protein levels both increased with H2O2 in a concentrationdependent manner, but decreased rapidly with high concentration of H2O2, and the changes were closely related to cell proliferation. Taken together, these findings argue our understanding on the role of oxidative stress and antioxidant in follicular development and ovarian aging.
卵巢衰老与活性氧水平升高及抗氧化防御功能缺陷有关。抗氧化过氧化物酶4(Prdx4)作为Prdx蛋白家族的一员,通过降低过氧化氢水平来控制细胞氧化应激。在先前的研究中,我们提供的证据表明,Prdx4在小鼠和人类卵巢中大量表达,且Prdx4在成熟卵泡中的表达高于未成熟卵泡。因此,我们推测Prdx4的表达可能与卵泡发育有关,并且它可能是卵泡发育中抗氧化机制的一部分。在本研究中,我们证明Prdx4主要在小鼠卵巢的颗粒细胞中表达,且其表达水平随着卵泡发育而显著增加。然而,当小鼠达到老年阶段(18个月龄)时,Prdx4的表达水平下降。同样,在人类卵巢中也发现了与小鼠研究中相似的模式,即绝经前女性的Prdx4表达低于年轻女性。随后的体外实验表明,Prdx4的mRNA和蛋白质水平均随过氧化氢浓度的增加而呈浓度依赖性升高,但在高浓度过氧化氢作用下迅速下降,且这些变化与细胞增殖密切相关。综上所述,这些发现有助于我们理解氧化应激和抗氧化剂在卵泡发育和卵巢衰老中的作用。