Progesterone and its receptor signaling in cervical remodeling: Mechanisms of physiological actions and therapeutic implications

Abstract

The remodeling of the cervix from a closed rigid structure to one that can open sufficiently for passage of a term infant is achieved by a complex series of molecular events that in large part are regulated by the steroid hormones progesterone and estrogen. Among hormonal influences, progesterone exerts a dominant role for most of pregnancy to initiate a loss of tissue strength yet maintain competence in a phase termed softening. Equally important are the molecular events that abrogate progesterone function in late pregnancy to allow a loss of tissue competence and strength during cervical ripening and dilation. In this review, we focus on current understanding by which progesterone receptor signaling for the majority of pregnancy followed by a loss/shift in progesterone receptor action at the end of pregnancy, collectively ensure cervical remodeling as necessary for successful parturition.

Keywords: Cervical remodeling; Cervix and cervical ripening; Pregnancy; Preterm birth; Progesterone; Progesterone receptor.

Figure 1:. Progesterone receptor (PR) localization in non-pregnant and pregnant cervix.

Immunohistochemical localization of PR in cervical sections of non-pregnant (NP), pregnant and postpartum (PP) mice. Epithelial PR is localized throughout the basal and luminal layers of squamous epithelia in the NP and PP cervix. Similar patterns are noted in cervical sections from gestation days 6 and 15 while basal layers have reduced PR expression relative to the luminal secretory cells on days 12 and 18. Stromal PR remains high throughout pregnancy and postpartum compared to non-pregnant cervix. Images are taken at 20X. E= Epithelia; S= Stroma.

Figure 2:. Progesterone and progesterone receptor signaling during cervical remodeling.