Bromocriptine inhibits proliferation in the endometrium from women with adenomyosis.

Autor:	Tang Y; Division of Neonatology, Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet, and WHO Collaborating Centre, Karolinska University Hospital, Stockholm, Sweden., Ponandai-Srinivasan S; Division of Neonatology, Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet, and WHO Collaborating Centre, Karolinska University Hospital, Stockholm, Sweden., Frisendahl C; Division of Neonatology, Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet, and WHO Collaborating Centre, Karolinska University Hospital, Stockholm, Sweden., Andersson JK; Division of Neonatology, Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet, and WHO Collaborating Centre, Karolinska University Hospital, Stockholm, Sweden., Pavone D; Division of Neonatology, Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet, and WHO Collaborating Centre, Karolinska University Hospital, Stockholm, Sweden., Stewart EA; Division of Reproductive Endocrinology and Infertility, Department of Obstetrics & Gynecology, Mayo Clinic, Rochester, MN, United States., Lalitkumar PGL; Division of Neonatology, Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet, and WHO Collaborating Centre, Karolinska University Hospital, Stockholm, Sweden., Korsching E; Institutet of Bioinformatics, University Hospital of Münster, University of Münster, Münster, Germany., Bogavarappu NR; Division of Neonatology, Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet, and WHO Collaborating Centre, Karolinska University Hospital, Stockholm, Sweden., Gemzell-Danielsson K; Division of Neonatology, Obstetrics and Gynecology, Department of Women's and Children's Health, Karolinska Institutet, and WHO Collaborating Centre, Karolinska University Hospital, Stockholm, Sweden.
Jazyk:	angličtina
Zdroj:	Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2023 Mar 09; Vol. 14, pp. 1026168. Date of Electronic Publication: 2023 Mar 09 (Print Publication: 2023).
DOI:	10.3389/fendo.2023.1026168
Abstrakt:	Objective: Bromocriptine treatment has been shown to reduce menstrual bleeding and pain in women with adenomyosis in a pilot clinical trial. The underlying mechanism contributing to the treatment effect is however unknown. The purpose of this study was to explore the effect of bromocriptine on the proliferation and migration properties of the endometrium in women with adenomyosis, by assessing cellular and molecular changes after six months of vaginal bromocriptine treatment. Methods: Endometrial specimens were collected during the proliferative phase from women with adenomyosis (n=6) before (baseline) and after six months of treatment with vaginal bromocriptine. Immunohistochemistry was used to determine changes in the protein expression of Ki67 in the endometrium of women with adenomyosis. Primary endometrial stromal cells isolated at baseline were expanded in vitro and exposed to different doses of bromocriptine to determine the optimal half-maximum inhibitory concentration (IC50) using CellTiter-Blue ® Cell Viability Assay. Cell proliferation was assessed by bromodeoxyuridine ELISA assay and Ki67 gene expression was checked by real-time PCR. The migratory ability of endometrial stromal cells was determined by wound healing and transwell migration assays. Small RNA sequencing was applied on tissues collected from women with adenomyosis before and after bromocriptine treatment to identify differentially expressed microRNAs (miRNAs) after bromocriptine treatment. Bioinformatic methods were used for target gene prediction and the identification of biological pathways by enrichment procedures. Results: Vaginal bromocriptine treatment reduced the Ki67 protein expression in the endometrium of women with adenomyosis and did not change the prolactin mRNA expression and protein concentration of prolactin in endometrial tissues. Bromocriptine significantly inhibited the proliferative and migrative abilities of endometrial stromal cells derived from women with adenomyosis in vitro . Moreover, small RNA sequencing revealed 27 differentially expressed miRNAs between the endometrium of women with adenomyosis before and after six months of vaginal bromocriptine treatment. KEGG pathway analysis on targeted genes of 27 miRNAs showed that several signaling pathways associated with cell proliferation and apoptosis were enriched after bromocriptine treatment. Conclusion: Bromocriptine treatment exhibits an anti-proliferative effect in the endometrium of women with adenomyosis in vivo and in vitro . Bromocriptine might inhibit the proliferation of endometrial tissue in adenomyosis in part through the regulation of dysregulated microRNAs and proliferation-associated signaling pathways. Competing Interests: ES receives active research support regarding adenomyosis R01HD105714 from the Eunice Kennedy Shriver Institute of Child Health and Human Development of the National Institutes of Health, Bethesda, MD USA, and serves as an Associate Editor for Frontiers in Reproductive Health. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Tang, Ponandai-srinivasan, Frisendahl, Andersson, Pavone, Stewart, Lalitkumar, Korsching, Bogavarappu and Gemzell-Danielsson.)
Databáze:	MEDLINE
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