The effects of oxidative stress on female reproduction: a review

Abstract

Oxidative stress (OS), a state characterized by an imbalance between pro-oxidant molecules including reactive oxygen and nitrogen species, and antioxidant defenses, has been identified to play a key role in the pathogenesis of subfertility in both males and females. The adverse effects of OS on sperm quality and functions have been well documented. In females, on the other hand, the impact of OS on oocytes and reproductive functions remains unclear. This imbalance between pro-oxidants and antioxidants can lead to a number of reproductive diseases such as endometriosis, polycystic ovary syndrome (PCOS), and unexplained infertility. Pregnancy complications such as spontaneous abortion, recurrent pregnancy loss, and preeclampsia, can also develop in response to OS. Studies have shown that extremes of body weight and lifestyle factors such as cigarette smoking, alcohol use, and recreational drug use can promote excess free radical production, which could affect fertility. Exposures to environmental pollutants are of increasing concern, as they too have been found to trigger oxidative states, possibly contributing to female infertility. This article will review the currently available literature on the roles of reactive species and OS in both normal and abnormal reproductive physiological processes. Antioxidant supplementation may be effective in controlling the production of ROS and continues to be explored as a potential strategy to overcome reproductive disorders associated with infertility. However, investigations conducted to date have been through animal or in vitro studies, which have produced largely conflicting results. The impact of OS on assisted reproductive techniques (ART) will be addressed, in addition to the possible benefits of antioxidant supplementation of ART culture media to increase the likelihood for ART success. Future randomized controlled clinical trials on humans are necessary to elucidate the precise mechanisms through which OS affects female reproductive abilities, and will facilitate further explorations of the possible benefits of antioxidants to treat infertility.

Associations between IVF outcomes and essential trace elements measured in follicular fluid and urine: a pilot study

“…The results were consistent with induction of Mn-based SOD activity, also associated with reduced FF ROS, and greater oocyte competence [14,15,41,44]. Similarly, higher FF Cu-Zn SOD is associated with an optimized follicular environment via reduced ROS [45]; a study of rat dams fed a Cu-deficient diet (<0.5 μg Cu/g) had decreased embryo quality compared to those fed a Cu-sufficient diet (8.0 μg Cu/g) [46]. However, a Japanese study of 41 oocytes reported no associations for 40 essential elements measured in human FF and fertilization or embryo quality [47].…”

Protein modification as oxidative stress marker in follicular fluid from women with polycystic ovary syndrome: the effect of inositol and metformin

“…It is believed that ROS over-production in the reproductive tract may significantly contribute to woman infertility mainly because of the ability of these molecules to exert a toxic effect decreasing oocyte quality [2,38,39]. The follicular fluid may be seen as a "biological window" which reflects all metabolic processes and hormonal microenvironment in which the oocyte matured [40].…”

“…Indeed, a whole spectrum of reproductive functions are modulated by ROS such as oocyte maturation, ovarian steroidogenesis, corpus luteum functions as well as fertilization, embryo development and pregnancy [1]. An imbalance between ROS production and the antioxidant defense systems, identifies an oxidative stress (OS) status, which may therefore be defined as a pathological condition caused by the displacement of the physiological balance between the production and the elimination of chemical oxidizing species [1].…”

“…OS has been also implicated in some conditions associated to infertility such as PCOS [2], a well known syndrome with systemic and reproductive implications characterized by a series of metabolic dysfunctions. Increasing evidence supports the central role of insulin resistance and compensatory hyperinsulinemia in the pathogenesis of the syndrome [3].…”

Endocrine disruptor & nutritional effects of heavy metals in ovarian hyperstimulation

“…An adequate intake of elements acting as enzyme co-factors for DNA synthesis and catalysing antioxidant reactions may be of significance; these elements are likely to have a role in folliculogenesis and oocyte maturation where DNA synthesis and reduction of harmful reactive oxygen species (ROS) are crucial processes [14]. However, the relevance of these elements to human infertility treatments is not clearly defined in the literature, particularly in the female.…”