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

Objective. To evaluate morphological changes and inflammatory events in the uterine cervix following presurgical treatment with the prostaglandin analogue misoprostol or the nitric oxide donor isosorbide mononitrate (IMN). Design. Experimental study. Settings. Sahlgrenska University Hospital, Gothenburg, Sweden. Population of sample. Primigravid women (n=32) scheduled for surgical termination of first trimester pregnancy, treated vaginally overnight with either misoprostol (200 g), IMN (40 mg) or no treatment (controls). Methods. Before evacuation, cervical biopsies were obtained with the use of a Tru-Cut biopsy needle. Morphology was studied by electron microscopy. For assessment of inflammatory events the expression of the matrix metalloproteinases MMP-1 and MMP-9 was estimated by immunohistochemistry and interleukin IL-8 was quantified by ELISA. Results. Misoprostol induced splitting and disorganization of the collagen fibres. Compared to specimens from women who had received no treatment, the granular endoplasmatic reticulum appeared enriched and dilated and the nuclear chromatin was clearly dispersed. Similar changes of a lesser degree were observed in specimens obtained from IMN-treated women. Staining intensity for MMP-1 and MMP-9 was more evident in specimens obtained from IMN-treated women compared to women who had received treatment with misoprostol or no treatment. The levels of IL-8 were higher following treatment with misoprostol compared to IMN and controls. Conclusion. 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.