Markers of Oxidative Stress and Miscarriage 氧化应激标记物与流产的关系

Miscarriage and pregnancy appear to be associated with increased oxidative stress.

流产和妊娠似乎与氧化应激增强有关。

In a successful pregnancy, however, changes occurred within the peripheral blood that offered protection from oxidant attach. The roles of the peripheral blood-plasma antioxidants thiol and ceruloplasmin-and two extracellular parameters – superoxide dismutase (SOD) and red cell lysate thiol have been examined in healthy pregnancy and in women suffering first-trimester miscarriage. It was found that pregnancies that went successfully to term were associated with increased levels of ceruloplasmin and SOD early in the first-trimester (1). These changes were thought to offer the cell protection from the damage caused by the increased oxidative stress associated with pregnancy. First-trimester miscarriage was associated with significantly reduced levels of SOD. A subgroup of patients who miscarried in the first pregnancy, but whose second pregnancies were successful, had higher levels of plasma thiol and significantly reduced levels of red cell lysate thiol in the on-going pregnancy compared to levels at the time of miscarriage.

在成功妊娠的案例中，外周血会发生变化，防止氧化剂附着。有研究分析了外周血的血浆抗氧化剂硫醇和酮蓝蛋白以及细胞外的超氧化物歧化酶和红细胞裂解物硫醇在正常妊娠女性和妊娠早期流产女性中的作用。结果发现，成功足月的妊娠与妊娠早期酮黄蛋白和超氧化物歧化酶水平升高有关(1)。这两种物质的增加可以保护细胞不受氧化应激增强对妊娠的危害。妊娠早期流产与超氧化物歧化酶水平显著降低有关。在第一次妊娠流产但第二次成功妊娠的患者中，第二次妊娠时患者的血浆硫醇水平比第一次妊娠高，红细胞裂解物硫醇水平显著降低。

The antioxidants Glutathione and glutathione transferase family of enzymes have been investigated in patients who experience recurrent pregnancy loss (2, 3). In a large case controlled study the relationship between recurrent pregnancy loss and polymorphisms in two genes, glutathione S-transferases M1 and T1, which are involved in the metabolism of a wide range of environmental toxins and carcinogens, was examined (3). The results suggested that women with GSTM1 null polymorphism may have an increased risk of recurrent pregnancy loss. In another study, elevated glutathione levels in pregnant patients with history of recurrent pregnancy loss were associated with pregnancy loss (2).

有研究探讨了经历反复妊娠丢失的患者中抗氧化剂谷胱甘肽和谷胱甘肽转移酶家族水平变化(2，3)。其中一项大型病例对照实验研究了反复妊娠丢失与两个基因(谷胱甘肽S-转移酶M1和T1)多态性之间的关系，这两个基因参与多种环境毒素和致癌物的代谢(3)。结果表明，具有谷胱甘肽 S-转移酶 M1无效多态性的患者反复妊娠丢失的风险增加。另一项研究则发现，反复妊娠丢失的患者谷胱甘肽水平升高与流产有关(2)。

Early pregnancy physiologic oxidative stress is associated with changes in placental protein production including angiogenic and anti-angiogenic placental proteins (4). Maternal serum soluble vascular endothelial growth factor receptor 1 and maternal serum placental growth factor have been found to be markedly decreased in threatened miscarriage patients who subsequently have a miscarriage suggesting these proteins are sensitive predictive markers of subsequent pregnancy loss (4).

妊娠早期生理性氧化应激与胎盘蛋白产生的变化有关，包括血管生成和抗血管生成胎盘蛋白(4)。研究发现母体血清可溶性血管内皮生长因子受体1和母体血清胎盘生长因子在随后发生流产的先兆流产患者中显著降低，这说明这些蛋白质是随后流产的敏感预测标记物(4)。

The primary recognized health risk from common deficiencies in glucose-6-phosphate dehydrogenase (G6PD) is non-immune red blood cell hemolysis. The protective role of the G6PD enzyme against oxidative stress has been demonstrated in animal studies (5). G6PD-deficient mice had higher embryonic DNA oxidation and more fetal death and birth defects. Embryopathies were prevented by protecting the embryos against oxidative stress and resulted in improved pregnancy outcome. G6PD enzyme deficiencies accordingly may have a broader biological relevance as important determinants of infertility, miscarriage, and teratogenesis.

6-磷酸葡萄糖脱氢酶(G6PD)常见缺陷导致的主要健康风险是非免疫性红细胞溶血。G6PD酶对氧化应激的保护作用已在动物研究中得到证实(5)。G6PD缺陷小鼠胚胎DNA氧化程度更高，胎儿死亡和出生缺陷更多。我们可以通过保护胚胎免受氧化应激来预防胚胎病，并改善妊娠结局。因此，G6PD 酶缺陷作为不孕症、流产和畸形的重要决定因素，可能具有更广泛的生物学相关性。

References

参考文献

1. Jequier AM, Ansell ID, Bullimore NJ. Congenital absence of the vasa deferentia presenting with infertility. J Androl 1985;6:15-9.

2. Brown DL, Benson CB, Doherty FJ, Doubilet PM, DiSalvo DN, Van Alstyne GA, Vickers MA, Loughlin KR. Cystic testicular mass caused by dilated rete testis: sonographic findings in 31 cases. AJR Am J roentgenol 1992;158(6): 1257-9.

3. Dubin L, Amelar RD. Varicocele size and results of varicocelectomy in selected subfertile men with varicocele. Fertil Steril 1970;21:606-9.

4. Chiou RK, Anderson JC, Wobig RK, Rosinsky DE, Matamoros A Jr, Chen WS, Taylor RJ. Color Doppler ultrasound criteria to diagnose varicoceles: correlation of a new scoring system with physical examination. Urology 1997;50:953-6.

5. Cina A, Minnetti M, Pirronti T, Vittoria Spampinato M, Canade A, Oliva G, Ribatti D, Bonomo L. Sonographic quantitative evalution of scrotal veins in healthy subjects: normative values and implications for the diagnosis of varicocele. Eur Urol 2006;50:345-50.