title: Diffused Intra-Oocyte Hydrogen Peroxide Activates Myeloperoxidase and Deteriorates Oocyte Quality.
abstract: Hydrogen peroxide (H2O2) is a relatively long-lived signaling molecule that plays an essential role in oocyte maturation, implantation, as well as early embryonic development. Exposure to relatively high levels of H2O2 functions efficiently to accelerate oocyte aging and deteriorate oocyte quality. However, little precise information exists regarding intra-oocyte H2O2 concentrations, and its diffusion to the oocyte milieu. In this work, we utilized an L-shaped amperometric integrated H2O2-selective probe to directly and quantitatively measure the real-time intra-oocyte H2O2 concentration. This investigation provides an exact measurement of H2O2 in situ by reducing the possible loss of H2O2 caused by diffusion or reactivity with other biological systems. This experiment suggests that the intra-oocyte H2O2 levels of oocytes obtained from young animals are reasonably high and remained constant during the procedure measurements. However, the intra-oocyte H2O2 concentration dropped significantly (40-50% reduction) in response to catalase pre-incubation, suggesting that the measurements are truly H2O2 based. To further confirm the extracellular diffusion of H2O2, oocytes were incubated with myeloperoxidase (MPO), and the diffused H2O2 triggered MPO chlorinating activity. Our results show that the generated hypochlorous acid (HOCl) facilitated the deterioration in oocyte quality, a process that could be prevented by pre-incubating the oocytes with melatonin, which was experimentally proven to be oxidized utilizing HPLC methods. This study is the first to demonstrate direct quantitative measurement of intracellular H2O2, and its extracellular diffusion and activation of MPO as well as its impact on oocyte quality. These results may help in designing more accurate treatment plans in assisted reproduction under inflammatory conditions.
authors.affiliation: Department of Obstetrics and Gynecology, The C, S, Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit Michigan, United States of America.
authors.forename: Sana N
authors.initials: SN
authors.lastname: Khan
authors.affiliation: Department of Obstetrics and Gynecology, The C, S, Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit Michigan, United States of America.
authors.forename: Faten
authors.initials: F
authors.lastname: Shaeib
authors.affiliation: Department of Obstetrics and Gynecology, The C, S, Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit Michigan, United States of America; Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Tohid
authors.initials: T
authors.lastname: Najafi
authors.affiliation: Department of Biomedical Engineering, Wayne State University, Detroit, Michigan, United States of America.
authors.forename: Mahendra
authors.initials: M
authors.lastname: Kavdia
authors.affiliation: Department of Obstetrics and Gynecology, The C, S, Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit Michigan, United States of America.
authors.forename: Bernard
authors.initials: B
authors.lastname: Gonik
authors.affiliation: Department of Obstetrics and Gynecology, The C, S, Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit Michigan, United States of America.
authors.forename: Ghassan M
authors.initials: GM
authors.lastname: Saed
authors.affiliation: Department of Obstetrics and gynecology, Division of Reproductive Endocrinology and Infertility, University of California Davis, Sacramento, California, United States of America, and California IVF Fertility Center, Davis and Sacramento, California, United States of America.
authors.forename: Pravin T
authors.initials: PT
authors.lastname: Goud
authors.affiliation: Department of Obstetrics and Gynecology, The C, S, Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit Michigan, United States of America; Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, Michigan, United States of America.
authors.forename: Husam M
authors.initials: HM
authors.lastname: Abu-Soud
mesh_terms: D000818:Animals; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000009:adverse effects / Q000493:pharmacokinetics*; D006997:Hypochlorous Acid / Q000378:metabolism; D051379:Mice; D009865:Oocytes / Q000187:drug effects* / Q000201:enzymology; D009195:Peroxidase / Q000378:metabolism*
chemical_list: D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D009195:Peroxidase