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期刊名称: Biology of Reproduction
Volume:87    Issue:6    
ISSN:0006-3363

Mono-(2-ethylhexyl) phthalate induces oxidative stress and inhibits growth of mouse ovarian antral follicles期刊论文

作者: Wang Wei Craig Zelieann R Basavarajappa Mallikarjuna S Hafner Katlyn S Flaws Jodi A
DOI:10.1095/biolreprod.112.102467

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被引频次: 47
出版者: OXFORD UNIV PRESS INC
期刊名称: Biology of Reproduction
ISSN: 0006-3363
卷期: Volume:87    Issue:6
语言: English
摘要: Mono-(2-ethylhexyl) phthalate (MEHP) is the active metabolite of the most commonly used plasticizer, di-(2-ethylhexyl) phthalate, and is considered to be a reproductive toxicant. However, little is known about the effects of MEHP on ovarian antral follicles. Thus, the present study tested the hypothesis that MEHP inhibits follicle growth via oxidative stress pathways. The data indicate that MEHP increases reactive oxygen species (ROS) levels and inhibits follicle growth in antral follicles, whereas N-acetylcysteine (NAC; an antioxidant) restores ROS levels to control levels and rescues follicles from MEHP-induced inhibition of follicle growth. To further analyze the mechanism by which MEHP induces oxidative stress and inhibits follicle growth, the expression and activities of various key antioxidant enzymes (copper/zinc superoxide dismutase [SOD1], glutathione peroxidase [GPX], and catalase [CAT]) and the expression of key cell-cycle regulators (Ccnd2, Ccne1, and Cdk4) and apoptotic regulators (Bcl-2 and Bax) were compared in control and MEHP-treated follicles. The data indicate that MEHP inhibits the expression and activities of SOD1 and GPX; does not inhibit Cat expression; inhibits the expression of Ccnd2, Ccne1, Cdk4, and Bcl-2; but increases the expression of Bax compared to controls. Furthermore, NAC blocks these toxic effects of MEHP. Collectively, these data suggest that MEHP induces oxidative stress by disrupting the activities of antioxidant enzymes. This may lead to decreased expression of cell-cycle regulators and antiapoptotic regulators and increased expression of proapoptotic factors, which then may lead to inhibition of follicle growth.
相关主题: Ovary, Oxidative stress, Toxicology, toxicology, REPRODUCTIVE-SYSTEM, GERM-CELL APOPTOSIS, KAPPA-B, HORMONAL-REGULATION, DI-(2-ETHYLHEXYL) PHTHALATE, RAT TESTIS, ovary, SUPEROXIDE-DISMUTASE EXPRESSION, REPRODUCTIVE BIOLOGY, LACTATIONAL EXPOSURE, DI(2-ETHYLHEXYL)PHTHALATE EXPOSURE, oxidative stress, MOLECULAR-MECHANISMS, Oxidoreductases - antagonists & inhibitors, Diethylhexyl Phthalate - antagonists & inhibitors, Reactive Oxygen Species - metabolism, RNA, Messenger - metabolism, Oxidoreductases - chemistry, Cell Cycle Proteins - antagonists & inhibitors, Ovarian Follicle - drug effects, Diethylhexyl Phthalate - toxicity, Infertility, Female - chemically induced, Diethylhexyl Phthalate - analogs & derivatives, Female, Free Radical Scavengers - therapeutic use, Acetylcysteine - therapeutic use, Ovarian Follicle - metabolism, Oxidoreductases - metabolism, Endocrine Disruptors - chemistry, Cell Cycle Proteins - metabolism, Cell Cycle Proteins - agonists, Plasticizers - toxicity, Random Allocation, Down-Regulation - drug effects, Mice, Inbred Strains, Infertility, Female - metabolism, Apoptosis Regulatory Proteins - metabolism, Endocrine Disruptors - toxicity, Up-Regulation - drug effects, Infertility, Female - pathology, Animals, Apoptosis Regulatory Proteins - antagonists & inhibitors, Apoptosis Regulatory Proteins - agonists, Infertility, Female - prevention & control, Mice, Oxidative Stress - drug effects, Ovarian Follicle - pathology,

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