Expression of connexin-43 and connexin-26 in the rat myometrium during pregnancy and labor is differentially regulated by mechanical and hormonal signals.

Abstract

We investigated the effects of uterine stretch on the levels of messenger RNA (mRNA) encoding the gap junction proteins connexin-43 (Cx-43) and connexin-26 (Cx-26) as well as the presence of gap junction plaques formed by Cx-43 within the myometrium. In nonpregnant ovariectomized rats, stretch of one uterine horn with a polyvinyl tube induced a significant increase in myometrial Cx-43 mRNA levels, an effect that was blocked by progesterone; no expression of Cx-26 was detected in the presence or absence of stretch. To investigate whether pregnancy and parturition modified the response to stretch, unilaterally pregnant rats underwent either sham operation or placement of a tube in the nongravid uterine horns. On day 20 of pregnancy, expression of Cx-43 mRNA in gravid horns was low, and stretch did not increase this level. Cx-26 mRNA expression was elevated at this time, but only in the gravid horns. Cx-43 mRNA was highly expressed in the myometrium of gravid horns during labor, but Cx-43 expression in sham-operated, nongravid horns remained low. In contrast, nongravid horns stretched with tubes expressed Cx-43 mRNA at levels similar to those in gravid horns. Levels of Cx-26 mRNA in gravid horns fell between days 20 and 23, and this was not altered by stretch. Punctate Cx-43 immunofluorescence (indicative of gap junction formation) also increased in the myometrium after uterine stretch and in gravid horns during labor. Our data demonstrate that differential mechanisms regulate the expression of Cx-43 and Cx-26 in the pregnant myometrium. Cx-43 expression during labor is dependent upon myometrial stretch under conditions of low progesterone. In contrast, Cx-26 expression during late pregnancy, although requiring the presence of the fetal/placental unit, does not require stretch of the myometrium.