Cervical priming in the first trimester: morphological and biochemical effects of misoprostol and isosorbide mononitrate

Abstract

The study demonstrates that misoprostol as well as IMN induces morphological changes and inflammatory events of the cervix. Changes of the collagen network were more pronounced in samples obtained from women treated with misoprostol compared to IMN.

Oral Misoprostol and Vaginal Isosorbide Mononitrate for Labor Induction

“…Recent basic science data demonstrate splitting and disorganization of cervical collagen fibers in women receiving vaginal isosorbide mononitrate and in women receiving vaginal misoprostol before first-trimester abortion. 23 Studies of the effects of oral misoprostol on the cervical collagen network are unfortunately lacking, and a lack of tissue effect at the level of the cervix with the use of oral misoprostol may explain our negative findings. Although the literature on oral misoprostol is not as extensive as that of vaginal misoprostol, our approach is based on the results of a published randomized trial conducted at our institution comparing a stepwise oral misoprostol protocol (50 micrograms followed by 100 micrograms in each subsequent dose) with standard vaginal administration (25 micrograms).…”

Prostaglandin-induced cervical remodelling in humans in the first trimester is associated with increased expression of specific tight junction, but not gap junction proteins

“…Their increased expression and mediation of trans-endothelial migration of T lymphocytes and macrophages [35], together with the reported recruitment by PG of chemotactic leukocytes [16] and mast cells [6], are strongly supportive of important roles for TJ in the regulation of vascular permeability [15,27,36] in the ECM during Misoprostol-induced CR.…”

“…Although findings vary with experimental models and species, CR is associated with increased stromal hydration [1], disorganization of collagen bundles [2,3] and altered concentrations of hyaluronic acid and dermatan sulphate [4]. During the final stages of CR, there is increased nitric oxide synthesis [5], with extravasation of leucocytes [6] and activated fibroblasts [7]. A role for the epithelium during CR is suggested by its expression of cyclo-oxygenase (COX)-2, interleukin-8 (IL-8), glucocorticoid receptors [7-9] and aquaporin channels [10].…”

“…Misoprostol, a synthetic 15-deoxy 16-hydroxy 16-methyl analogue of natural PG-E1 has been the drug of choice due to its effectiveness, low cost and minimal side effects at a dose of 400 micrograms (μg) for 3 hours [11,14]. Human cervical biopsy studies in 1st trimester suggest that exogenous PG induces CR by causing disorganization of collagen, vasodilatation, increasing stromal leukocytes, and stimulating the release of pro-inflammatory cytokines [6,15,16]. However the mechanisms by which vaginally administered PG induces these changes in the extracellular matrix are not fully established.…”

Can isosorbide mononitrate be useful in second trimester termination of pregnancies?

“…NO seems to be involved in many of these mechanisms. For example, NO donors increase preinflammatory cytokine interleukin-8 local expression [3,5]. In the necessary step of collagen degradation, MMPs are involved, and NO can induce MMP-1 production [5,6] and possibly MMP-9 [5].…”