title: Reactive oxygen species are indispensable in ovulation.
abstract: Ovulation is stimulated by the preovulatory surge of the pituitary luteinizing hormone (LH). Because the ovulatory response is commonly identified with inflammation, we explored the involvement of reactive oxygen species (ROS) in this process. Our experiments show that administration of broad-range scavengers of oxidative species into the ovarian bursa of mice, hormonally induced to ovulate, significantly reduced the rate of ovulation. LH-induced cumulus mucification/expansion, a necessary requirement for ovulation, was prevented by antioxidants both in vivo and in an ex vivo system of isolated intact ovarian follicles. Along this line, H(2)O(2) fully mimicked the effect of LH, bringing about an extensive mucification/expansion of the follicle-enclosed cumulus-oocyte complexes. Impaired progesterone production was observed in isolated follicles incubated with LH in the presence of the antioxidant agents. Furthermore, LH-stimulated up-regulation of genes, the expression of which is crucial for ovulation, was substantially attenuated upon ROS ablation. This system was also used for demonstrating the role of ROS in phosphorylation and activation of the EGF receptor as well as its downstream effector, p42/44 MAPK. Together, our results provide evidence that ovarian production of ROS is an essential preovulatory signaling event, most probably transiently triggered by LH.
authors.affiliation: Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ketty
authors.initials: K
authors.lastname: Shkolnik
authors.forename: Ari
authors.initials: A
authors.lastname: Tadmor
authors.forename: Shifra
authors.initials: S
authors.lastname: Ben-Dor
authors.forename: Nava
authors.initials: N
authors.lastname: Nevo
authors.forename: Dalia
authors.initials: D
authors.lastname: Galiani
authors.forename: Nava
authors.initials: N
authors.lastname: Dekel
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D002083:Butylated Hydroxyanisole / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006062:Gonadotropins / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism; D010060:Ovulation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D016877:Oxidants / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011374:Progesterone / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046509:Tissue Culture Techniques
chemical_list: D000975:Antioxidants; D006062:Gonadotropins; D016877:Oxidants; D017382:Reactive Oxygen Species; D002083:Butylated Hydroxyanisole; D011374:Progesterone; D007986:Luteinizing Hormone; D006861:Hydrogen Peroxide; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D000111:Acetylcysteine