title: The hormonal herbicide, 2,4-dichlorophenoxyacetic acid, inhibits Xenopus oocyte maturation by targeting translational and post-translational mechanisms.
abstract: The widely used hormonal herbicide, 2,4-dichlorophenoxyacetic acid, blocks meiotic maturation in vitro and is thus a potential environmental endocrine disruptor with early reproductive effects. To test whether maturation inhibition was dependent on protein kinase A, an endogenous maturation inhibitor, oocytes were microinjected with PKI, a specific PKA inhibitor, and exposed to 2,4-D. Oocytes failed to mature, suggesting that 2,4-D is not dependent on PKA activity and likely acts on a downstream target, such as Mos. De novo synthesis of Mos, which is triggered by mRNA poly(A) elongation, was examined. Oocytes were microinjected with radiolabelled in vitro transcripts of Mos RNA and exposed to progesterone and 2,4-D. RNA analysis showed progesterone-induced polyadenylation as expected but none with 2,4-D. 2,4-D-activated MAPK was determined to be cytoplasmic in localization studies but poorly induced Rsk2 phosphorylation and activation. In addition to inhibition of the G2/M transition, 2,4-D caused abrupt reduction of H1 kinase activity in MII phase oocytes. Attempts to rescue maturation in oocytes transiently exposed to 2,4-D failed, suggesting that 2,4-D induces irreversible dysfunction of the meiotic signaling mechanism.
authors.affiliation: Department of Biology, Willamette University, Salem, OR 97301, USA.
authors.forename: Alexis M
authors.initials: AM
authors.lastname: LaChapelle
authors.forename: Michael L
authors.initials: ML
authors.lastname: Ruygrok
authors.forename: MaryEllen
authors.initials: M
authors.lastname: Toomer
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Oost
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Monnie
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Swenson
authors.forename: Alex A
authors.initials: AA
authors.lastname: Compton
authors.forename: Barbara
authors.initials: B
authors.lastname: Stebbins-Boaz
mesh_terms: D015084:2,4-Dichlorophenoxyacetic Acid / Q000633:toxicity*; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D006540:Herbicides / Q000633:toxicity*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008540:Meiosis / Q000187:drug effects* / Q000502:physiology; D017232:Oncogene Proteins v-mos / Q000096:biosynthesis / Q000235:genetics; D009865:Oocytes / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology; D014176:Protein Biosynthesis / Q000187:drug effects*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism / Q000494:pharmacology; D014982:Xenopus laevis
chemical_list: D006540:Herbicides; D017232:Oncogene Proteins v-mos; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D015084:2,4-Dichlorophenoxyacetic Acid; D011374:Progesterone