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Roles of reactive oxygen species and antioxidants in ovarian toxicity

Devine, Patrick, Perreault, Sally and Luderer, Ulrike (2012) Roles of reactive oxygen species and antioxidants in ovarian toxicity. Biology of Reproduction, 86 (2). p. 27. ISSN 0006-3363

Abstract

Proper functioning of the ovary is critical to maintain fertility and overall health, and ovarian
function depends on the maintenance and normal development of ovarian follicles. This review
presents evidence about the potential impact of oxidative stress on the well-being of primordial,
growing and preovulatory follicles, as well as oocytes and early embryos, examining cell types
and molecular targets. Limited data from genetically modified mouse models suggest that several
antioxidant enzymes, which protect cells from reactive oxygen species (ROS), may play
important roles in follicular development and/or survival. Exposures to agents known to cause
oxidative stress, such as gamma-irradiation, chemotherapeutic drugs, or polycyclic aromatic
hydrocarbons, induce rapid primordial follicle loss; however, the mechanistic role of ROS has
received limited attention. In contrast, ROS may play an important role in the initiation of
apoptosis in antral follicles. Depletion of glutathione leads to atresia of antral follicles in vivo
and apoptosis of granulosa cells in cultured antral follicles. Chemicals, such as
cyclophosphamide, dimethylbenzanthracene, and methoxychlor, increase proapoptotic signals,
preceded by increased ROS and signs of oxidative stress; and co-treatment with antioxidants is
protective. In oocytes, glutathione levels change rapidly during progression of meiosis and early
embryonic development, and high oocyte glutathione at the time of fertilization is required for
male pronucleus formation and for embryonic development to the blastocyst stage. Because
current evidence suggests that oxidative stress can have significant negative impacts on female
fertility and gamete health, dietary or pharmacological intervention may prove to be effective
strategies to protect female fertility.

Item Type: Article
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Keywords: ovary, toxicology, fertility, oocyte, follicle, oxidative stress, ROS
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Date Deposited: 13 Oct 2015 13:15
Last Modified: 13 Oct 2015 13:15
URI: https://oak.novartis.com/id/eprint/5729

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