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- W2895566723 abstract "Methamidophos (MET) is an organophosphate (OP) pesticide widely used in agriculture in developing countries. MET causes adverse effects in male reproductive function in humans and experimental animals, but the underlying mechanisms remain largely unknown. We explored the effect of MET on mice testes (5 mg/kg/day/4 days), finding that this pesticide opens the blood-testis barrier and perturbs spermatogenesis, generating the appearance of immature germ cells in the epididymis. In the seminiferous tubules, MET treatment changed the level of expression or modified the stage-specific localization of tight junction (TJ) proteins ZO-1, ZO-2, occludin, and claudin-3. In contrast, claudin-11 was barely altered. MET also modified the shape of claudin-11, and ZO-2 at the cell border, from a zigzag to a more linear pattern. In addition, MET diminished the expression of ZO-2 in spermatids present in seminiferous tubules, induced the phosphorylation of ZO-2 and occludin in testes and reduced the interaction between these proteins assessed by co-immunoprecipitation. MET formed covalent bonds with ZO-2 in serine, tyrosine and lysine residues. The covalent modifications formed on ZO-2 at putative phosphorylation sites might interfere with ZO-2 interaction with regulatory molecules and other TJ proteins. MET bonds formed at ZO-2 ubiquitination sites likely interfere with ZO-2 degradation and TJ sealing, based on results obtained in cultured epithelial cells transfected with ZO-2 mutated at a MET target lysine residue. Our results shed light on MET male reproductive toxicity and are important to improve regulations regarding the use of OP pesticides and to protect the health of agricultural workers." @default.
- W2895566723 created "2018-10-12" @default.
- W2895566723 creator A5002433394 @default.
- W2895566723 creator A5009652619 @default.
- W2895566723 creator A5038878986 @default.
- W2895566723 creator A5040629418 @default.
- W2895566723 creator A5062231826 @default.
- W2895566723 creator A5065704241 @default.
- W2895566723 creator A5077461434 @default.
- W2895566723 creator A5088709113 @default.
- W2895566723 date "2018-12-01" @default.
- W2895566723 modified "2023-10-17" @default.
- W2895566723 title "The organophosphate pesticide methamidophos opens the blood-testis barrier and covalently binds to ZO-2 in mice" @default.
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