Date of Award

8-1985

Degree Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

Department

Medical Sciences

Supervisor

Professor Robert E. Garfield

Abstract

Regular, coordinated contractions of uterine smooth muscle are thought to facilitate the delivery of the fetus(es) at parturition. The development of synchronous activity at term follows the development of many, large gap junctions between uterine smooth muscle cells. The objectives of this thesis were to test the hypothesis that the formation of gap junctions improves direct intercellular communication between the muscle fibers and to determine whether the functional properties of the junctions are regulated. Increased intercellular communication in uterine tissues may facilitate synchronous activity during labor and the regulation of such cell-cell interactions by modulating the function of the gap junctions may participate in the control of uterine contractility during pregnancy and parturition.

A technique was developed to study the diffusion of a small radiolabelled glucose analog, 2-deoxyglucose, through small strips of myometrium. Tissues with many gap junctions from rats in labor demonstrated a significantly greater redistribution of tracer compared to muscle removed from days 17-20 pregnant and days 2-3 post partum animals not in labor which had few junctions. This movement of tracer was shown to be the result of intracellular and direct, cell-to-cell diffusion. Thus, there is evidence for improved intercellular communication in the myometrium during parturition when gap junctions are present.

The extent of intercellular communication in the parturient myometrium was reduced by elevating the intracellular concentrations of Ca⁺⁺ and cyclic AMP in the absence of a change in the extent of gap junctions. More significantly, however, reduced communication was shown in tissues exposed to specific agents which are thought to play a role in the regulation of pregnancy and parturition. Thus, in addition to providing for the increase in gap junctions in the myometrium at term, the hormonal alterations which precede and accompany labor may also regulate the functional properties of these cell-to-cell membrane channels.

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