title: Oocyte maturation in Xenopus laevis is blocked by the hormonal herbicide, 2,4-dichlorophenoxy acetic acid.
abstract: Oocyte maturation is dependent on a complex program of morphological, ultrastructural, and biochemical signaling events, and if disrupted could lead to decreased fertility and population decline. The in vitro sensitivity of amphibian oocytes and oocyte maturation to plant growth factor and widely used hormonal herbicide, 2,4-dichlorophenoxyacetic acid (2,4-D), was examined in this study to determine its potential impact on early development and possible contribution to the global amphibian decline. Progesterone, which acts through a membrane receptor, triggers meiotic maturation in full grown (stage VI) Xenopus oocytes, characterized by cytoskeletal reorganization, nuclear dissolution, chromosome condensation, and spindle formation. Biochemically, the Mos/MAPK/MPF signaling pathway is activated, in part dependent on translational activation of specific maternal mRNAs such as c-Mos. Light microscopy revealed unusual asymmetric morphotypes in oocytes exposed to 2,4-D alone characterized by a white spot and bulge, termed coning, in the animal pole where the germinal vesicle (nucleus) persisted intact. Treatment of oocytes with cytochalasin B, a microfilament inhibitor, blocked these morphotypes but nocodazole, a microtubule depolymerizing agent, did not. Confocal microscopy showed that 2,4-D, itself, caused substantial depolymerization of perinuclear microtubules. Importantly, 2,4-D blocked progesterone-induced maturation as measured by the lack of nuclear breakdown, confirmed by the lack of Mos expression, MPF activation, and cytoplasmic polyadenylation of cyclin B1 mRNA. However, Western blot analysis and U0126 inhibitor studies showed that 2,4-D, either alone or in the presence of progesterone, induced MAPK phosphorylation through MAPKK. These results show that 2,4-D disrupts oocyte cytoskeletal organization and blocks maturation while stimulating an independent MAPK signaling pathway.
authors.affiliation: Department of Biology, Willamette University, Salem, Oregon 97301, USA. bstebbin@willamette.edu
authors.forename: Barbara
authors.initials: B
authors.lastname: Stebbins-Boaz
authors.forename: Katherine
authors.initials: K
authors.lastname: Fortner
authors.forename: Jessie
authors.initials: J
authors.lastname: Frazier
authors.forename: Suzanne
authors.initials: S
authors.lastname: Piluso
authors.forename: Samuel
authors.initials: S
authors.lastname: Pullen
authors.forename: Melissa
authors.initials: M
authors.lastname: Rasar
authors.forename: William
authors.initials: W
authors.lastname: Reid
authors.forename: Kristin
authors.initials: K
authors.lastname: Sinclair
authors.forename: Elisa
authors.initials: E
authors.lastname: Winger
mesh_terms: D015084:2,4-Dichlorophenoxyacetic Acid / Q000633:toxicity*; D000818:Animals; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects; D005260:Female; D006540:Herbicides / Q000633:toxicity*; D066298:In Vitro Techniques; D020935:MAP Kinase Signaling System / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D006540:Herbicides; D012333:RNA, Messenger; D015084:2,4-Dichlorophenoxyacetic Acid; D011374:Progesterone