title: Misoprostol modulates the gene expression prostaglandin E2 and oxidative stress markers in myometrial cells.
abstract: Misoprostol, prostaglandin E1 analogue, used for labour induction. However, one-third of patients who have labour induced with prostaglandins do not reach vaginal delivery. The differential expression of prostaglandin receptors in myometrial cells could account for this differential response. Since delivery physiology also involves modulation of oxidative metabolism that can be potentially affected by pharmacological drugs, in the present investigation the role of misoprostol on expression of prostaglandin receptors, and oxidative markers of myometrial cells was evaluated. Samples of myometrial tissues procured from women with spontaneous (SL) and nonspontaneous (NSL) labours were cultured in vitro and exposed to different concentrations of misoprostol. Gene expression was evaluated by qRT-PCR and oxidative biomarkers were evaluated by spectrophotometric and fluorometric analysis. Cells from SL women presented greater responsiveness to misoprostol, since an upregulation of genes related to increased muscle contraction was observed. Otherwise, cells from NSL women had low responsiveness to misoprostol exposure or even a suppressive effect on the expression of these genes. Oxidative biomarkers that previously have been related to labour physiology were affected by misoprostol treatment: lipoperoxidation and protein carbonylation (PC). However, a decrease in lipoperoxidation was observed only in SL cells treated with low concentrations of misoprostol, whereas a decrease of PC occurred in all samples treated with different misoprostol concentrations. The results suggest a pharmacogenetic effect of misoprostol in labour induction involving differential regulation of EP receptor genes, as well as some minor differential modulation of oxidative metabolism in myometrial cells.
authors.affiliation: Graduating Program in Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Av. Roraima 1000, Prédio 21, Zip code: 97105-900 Santa Maria-RS, Brazil; Department of Gynecology and Obstetrics, Center of Health Sciences, Federal University of Santa Maria, Av. Roraima 1000, Prédio 26, Zip code: 97105-900 Santa Maria, RS, Brazil. Electronic address: cristinekollingkonopka@hotmail.com.
authors.forename: Cristine Kolling
authors.initials: CK
authors.lastname: Konopka
authors.affiliation: Graduating Program in Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Av. Roraima 1000, Prédio 21, Zip code: 97105-900 Santa Maria-RS, Brazil. Electronic address: azzolinveronica@hotmail.com.
authors.forename: Verônica Farina
authors.initials: VF
authors.lastname: Azzolin
authors.affiliation: Graduating Program in Toxicological Biochemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, Av. Roraima 1000, Prédio 18, Zip code: 97105-900 Santa Maria-RS, Brazil. Electronic address: fran.cine.bio@hotmail.com.
authors.forename: Francine Carla
authors.initials: FC
authors.lastname: Cadoná
authors.affiliation: Graduating Program in Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Av. Roraima 1000, Prédio 21, Zip code: 97105-900 Santa Maria-RS, Brazil. Electronic address: alencarkolinski@yahoo.com.br.
authors.forename: Alencar Kolinski
authors.initials: AK
authors.lastname: Machado
authors.affiliation: Graduating Program in Toxicological Biochemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, Av. Roraima 1000, Prédio 18, Zip code: 97105-900 Santa Maria-RS, Brazil. Electronic address: dornellesedu@gmail.com.
authors.forename: Eduardo Bortoluzzi
authors.initials: EB
authors.lastname: Dornelles
authors.affiliation: Graduating Program in Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Av. Roraima 1000, Prédio 21, Zip code: 97105-900 Santa Maria-RS, Brazil. Electronic address: fernandabarbisan@gmail.com.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Barbisan
authors.affiliation: Program in Pharmacology, Center of Health Sciences, Federal University of Santa Maria, Av. Roraima 1000, Prédio 21, Zip code: 97105-900 Santa Maria-RS, Brazil. Electronic address: ibmcruz@hotmail.com.
authors.forename: Ivana Beatrice Mânica
authors.initials: IB
authors.lastname: da Cruz
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D015232:Dinoprostone / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D016595:Misoprostol / Q000494:pharmacology*; D009215:Myometrium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects*; D011247:Pregnancy; D014590:Uterine Contraction / Q000187:drug effects
chemical_list: D015415:Biomarkers; D016595:Misoprostol; D015232:Dinoprostone
keywords: Myometrium; Pharmacogenomic; Prostaglandin receptors; Term pregnancy; Uterus; mRNA