Environment, Nutrition, Toxicology and Reproduction
(M229) 2,2′–DICHLOROBIPHENYL DECREASES AMPLITUDE AND SYNCHRONIZATION OF UTERINE CONTRACTIONS THROUGH MAPK–MEDIATED PHOSPHORYLATION OF CONNEXIN43.
Chung, Daesuk1, Loch-Caruso, Rita1, 1 University of Michigan, Ann Arbor, MI
ABSTRACT- Previously, we reported that uterine strips from gestation day (GD) 10 pregnant rats exposed to 2,2′–dichlorobiphenyl (2,2′–DCB) decreased the amplitude and the synchronization of contraction and that MAPK–induced phosphorylation of connexin43 (Cx43) results in 2,2′–DCB–induced inhibition of gap junction communication between myometrial cells. The present study examined the hypothesis that inhibition of myometrial gap junctions through MAPK–induced phosphorylation of Cx43 leads to 2,2′–DCB–induced modification of uterine contractions. To examine whether 2,2′–DCB–induced modification of uterine contractions is dependent on the MEK–MAPK pathway, the pattern of uterine contraction was observed in uterine strips cotreated with 100 M 2,2′–DCB and the MEK inhibitor PD98059 (5 M). Decrease in amplitude and desynchronization of contractions reversed significantly 2 h after cotreatment. In order to see whether MAPK–induced phosphorylation of Cx43 is the mechanism for 2,2′–DCB–induced modification of uterine contractions, western blot of Cx43 phosphorylated at ser255 by MAPK was compared in uterine strips untreated or exposed to 0.1% DMSO (solvent control), 100 M 2,2′–DCB or 100 M 2,2′–DCB and 5 M PD98059 for 1 h. Densitometric analysis of uterine tissue showed about a two–fold increase of Cx43 phosphorylated at ser255 relative to GAPDH after exposure to 100 M 2,2′–DCB. This 2,2′–DCB–induced phosphorylation of Cx43(S255) was prevented by cotreating uterine strips exposed with 100 M 2,2′–DCB and 5 M PD98059. Therefore, this study suggests that 2,2′–DCB decreases amplitude and synchronization of uterine contractions through MAPK–mediated phosphorylation of Cx43.
KEY WORDS: 2,2′–dichlorobiphenyl, uterine contractions, MAPK, connexin43