Morphological and electrophysiological studies have demonstrated that functional myometrial gap junctions are normally absent or are present in very low numbers except at parturition in preterm or in normal term labor suggesting that gap junctions may be necessary but not sufficient for the propagation of action potentials and for the ontogeny of synchronous contractile activity required for parturition. Studies in our laboratory support this hypothesis and provide a basis for analysis of the modulation of a myometrial gap junction protein and gap junctions at preterm and term labor. We have recently developed antibodies to specific amino acid sequences within the myometrial gap junction protein, connexin 43 (CX43) and have found that these antibodies can be utilized in immunocytochemical analysis of the cellular distribution of CX43 and are also useful in the quantitative assessment of CX43 in an ELISA. We have found that the synthesis of myometrial CX43 in timed pregnant rats begins between the 18th and 19th day of pregnancy and rises to a maximum 12 hours prior to delivery, but that recognizable gap junctions do not appear at the plasma membrane until the day of parturition. We believe that transport of CX43 to the plasma membrane may be a penultimate step in the cascade that leads to effective labor. We have also found that gap junction protein and gap junctions can be induced in the myometrium of immature nonpregnant rats after 6 daily estrogen injections (500 mug/da), in ovariectomized pregnant rats, ovariectomized rats treated with 500 mug/da estrogen, or treated with RU486. We propose in the present study to further analyze the relationship between the development or cessation of synchronous contractile activity and 1) the kinetics and temporal pattern of CX43 synthesis, trafficking, and assembly in the myometrium, and 2) the hormonal, regulation of the expression and loss of functional gap junctions in rat and human myometrium.

Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Cincinnati
Department
Type
DUNS #
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
Brodt-Eppley, J; Myatt, L (1999) Prostaglandin receptors in lower segment myometrium during gestation and labor. Obstet Gynecol 93:89-93
Moore, S D; Brodt-Eppley, J; Cornelison, L M et al. (1999) Expression of prostaglandin H synthase isoforms in human myometrium at parturition. Am J Obstet Gynecol 180:103-9
Skannal, D G; Eis, A L; Brockman, D et al. (1997) Immunohistochemical localization of phospholipase A2 isoforms in human myometrium during pregnancy and parturition. Am J Obstet Gynecol 176:878-82
Myatt, L; Langdon, G; Brockman, D E (1994) Identification and changes in concentrations of prostaglandin H synthase (PGHS) isoforms in rat myometrium at parturition. Prostaglandins 48:285-96