Journal or Publishing Institution: Reproductive Toxicology
Study: http://www.ncbi.nlm.nih.gov/pubmed/17055699
Author(s): LaChapelle, A.M., Ruygrok, M.L., Toomer, M., Oost, J.J., Monnie, M.L., Swenson, J.A., Compton, A.A. and Stebbins-Boaz, B.
Article Type: Peer Reviewed Study
Record ID: 1344
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.
Keywords: Oocyte maturation, Signal transduction, PKA, Mos, MAPK, Cytoplasmic polyadenylation, Endocrine disruptor, 2,4-D; 2,4-Dichlorophenoxyacetic Acid, Animals, Cell Cycle, Combination Drug Therapy, Female, Herbicides, MAP Kinase Signaling System, Meiosis, Oncogene Proteins v-mos, Oocytes, Progesterone, Protein Biosynthesis, Protein Kinase Inhibitors, Post-Translational Protein Processing, Messenger RNA, Xenopus laevis; Toxicity, Drug Effects, Physiology, Biosynthesis, Genetics, Growth & Development, Pharmacology, Metabolism
Citation: LaChapelle, A.M., Ruygrok, M.L., Toomer, M., Oost, J.J., Monnie, M.L., Swenson, J.A., Compton, A.A. and Stebbins-Boaz, B., 2007. The hormonal herbicide, 2, 4-dichlorophenoxyacetic acid, inhibits Xenopus oocyte maturation by targeting translational and post-translational mechanisms. Reproductive Toxicology, 23(1), pp.20-31.
