Human fetal membranes inhibit calcium L-channel activated uterine contractions.

Abstract

Paracrine signals among fetal membranes, decidua, and uterus play an important role in the initiation of parturition in women. In previous work we demonstrated that fetal membranes inhibit uterine contractions. In the current study we test the hypothesis that the fetal membranes decrease uterine contractions by inhibition of the uterine calcium L-channel. Our dual-chamber fetal membrane-uterine muscle in vitro model was used in this study. Rat uterine muscle strips were anchored into the maternal sides of the chambers. Fetal membranes (or Parafilm controls) were added to the chamber in a removable cassette. Uterine contractions were stimulated with the specific calcium L-channel agonist Bay K 8644. When uterine muscle was exposed to full-thickness fetal membranes (amnion-chorion with attached decidua) or to the intact fetal components (chorion-amnion) or to chorion alone, the Bay K 8644 dose-response curve was significantly shifted to the right. When uterine muscle was exposed to amnion alone or to the decidua alone, the Bay K 8644 dose-response curve was not shifted. Fetal membranes, did not cause a shift in the ionomycin (a calcium ionophore) dose-response curve. These results support the hypothesis and provide evidence that human fetal membranes, most likely chorion, release an endogenous calcium L-channel inhibitor.