**2. Reactive Oxygen Species (ROS)**

The ROS have physiological and pathological functions in the female reproductive tract. Fertility problems related to ROS have etiopathogenic factors in common (Agarwal et al., 2005). These reactive species are generated through enzymatic and non-enzymatic organic reactions. Biological reactions, through electron transference or through oxigenase, that use

Endometriosis and Infertility: The Role of Oxidative Stress 401

The superoxide anion is produced by a one-electron reduction of an oxygen molecule and initiates a radical chain reaction. It is believed that SOD, which dismutates the superoxide anion to hydrogen peroxide (2 O2- + 2 H+ **→** H2O2 + O2), plays a central role in antioxidant

• SOD3, which encodes the extracellular form (EC-SOD), structurally similar to CuZn-

One of the striking phenotypes of SOD1-deficient mice is female infertility, suggesting a potential role of this enzyme in female fertility. SOD2 is inducible under various oxidative stress and inflammatory conditions. EC-SOD is present at high levels in the epididymis,

The presence of SOD was evidenced in human follicular fluid (FF) and the identification of high concentrations of SOD in FF was associated with oocytes that were not fertilized (Sabatini et al., 1999). Data of a recently published study showed that SOD activity decreased with age in women, but increased in women with endometriosis and ovulatory dysfunction (Matos et al., 2009). When the cause of infertility was male factor, the success of ART was associated with increased SOD activity. Variations in SOD activity emphasize the importance of oxidative stress in the oocyte maturation process, and are suggested to be a

A recent study has established a threshold level in FF which ROS may be considered toxic for viable embryo formation and pregnancy outcome. ROS, lipid peroxidation and total antioxidant capacity were estimated. The upper cut-off ROS level beyond which viable embryo formation is not favorable was found to be approximately 107 cps/400 microl FF. This level, determined in women with tubal factor infertility, was further validated in women with endometriosis and PCOS and correlated with fertilization and pregnancy rate

**Catalase** exclusively detoxifies hydrogen peroxide and has no requirement for an electron donor **(2 H2O2 → 2 H2O + O2)**. It plays a role in organs such as the liver, but its specific

Glutathione is a tripeptidyl molecule and is present in either the reduced (GSH) or the oxidized state (GSSG). It plays pleiotropic roles, which include the maintenance of cells in a reduced state and the formation of conjugates with some harmful endogenous and xenobiotic compounds. In addition, GSH serves as an electron donor for GPx that reduces peroxide **(2GSH + H2O2 → GSSG + 2 H2O)**. At least four selenium-containing GPx

The cytosolic form, GPX1, is widely distributed in tissues and has been the most extensively investigated form. However, GPX1-knockout mice show no abnormality in phenotype

reactions. Three isozymes are produced by mammals (Fujii et al., 2005):

seminiferous tubules of the testis, as well as the lungs (Fujii et al., 2005).

• SOD1 encodes Cu,Zn-SOD, which is largely cytosolic; • SOD2 encodes Mn-SOD, a mitochondrial isoform;

potential biomarker of ART success (Matos et al., 2009).

function in the genital tract is largely unknown (Fujii et al., 2005).

isozymes are produced in mammals (Fujii et al., 2005):

including reproductive capability (Ho et al., 1997);

and embryo quality (Jana et al., 2010).

• **Peroxidases:** 

• **Superoxide dismutase (SOD):** 

SOD.

oxygen (O2) as substrate, generate large amounts of ROS. As the mithocondrial respiratory chain is the major O2 cell intake system, the majority of ROS are produced by this system under physiological conditions (Fujii et al., 2005). The **superoxide radical (O2 -)** is formed when electrons leak from the electron transport chain (O2 + e- **→** O2 -) (Agarwal et al., 2005). The dismutation of superoxide results in the formation of **hydrogen peroxide (H2O2)** (2 O2 - + 2 H+ **→**H2O2 + O2) (Agarwal et al., 2005). The same can also be generated by reduction of O2 - (O2- + e- + 2 H+ **→**H2O2) (Babior, 1997). The **hidroxyl (OH- ) ion** is formed by the acquisition of 1 electron by **H2O2** (H2O2 + e- + H+ **→**OH + H2O) (Babior, 1997). The hydroxyl ion is highly reactive and can modify purines and pyrimidines and cause strand breaks resulting in DNA damage (Agarwal et al., 2005).
