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- Boggavarapu, NR, et al.
(författare)
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Compartmentalized gene expression profiling of receptive endometrium reveals progesterone regulated ENPP3 is differentially expressed and secreted in glycosylated form
- 2016
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6, s. 33811-
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Tidskriftsartikel (refereegranskat)abstract
- The complexity of endometrial receptivity at the molecular level needs to be explored in detail to improve the management of infertility. Here, differential expression of transcriptomes in receptive endometrial glands and stroma revealed Ectonucleotide Pyrophosphatase/Phosphodiesterase 3 (ENPP3) as a progesterone regulated factor and confirmed by various methods, both at mRNA and protein level. The involvement of ENPP3 in embryo attachment was tested in an in vitro model for human embryo implantation. Interestingly, there was high expression of ENPP3 mRNA in stroma but not protein. Presence of N-glycosylated ENPP3 in receptive phase uterine fluid in women confirms its regulation by progesterone and makes it possible to use in a non-invasive test of endometrial receptivity.
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- Lalitkumar, P. G. L, et al.
(författare)
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Mifepristone, but not levonorgestrel, inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model
- 2007
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 22:11, s. 3031-3037
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The use of fertility regulating drugs is limited among various socio-ethnic groups due to limited knowledge about their mechanism of action. This study investigates the effect of levonorgestrel and mifepristone on attachment of human embryos to an in vitro endometrial construct. METHOD: Three-dimensional endometrial constructs were established by co-culturing early luteal phase human endometrial stromal and epithelial cells. Expression of endometrial receptivity markers in this construct were examined by immunohistochemistry. Effects of mifepristone and levonorgestrel on viability and attachment of human blastocysts were investigated. RESULTS: Endometrial constructs expressed the factors involved in endometrial receptivity: estrogen receptor, progesterone receptor, vascular endothelial growth factor, leukemia inhibitory factor, interleukin-1, COX-2, MUC-1 and integrin-alpha(V)beta(3). None of the 15 embryos cultured with mifepristone attached to the endometrial construct (P < 0.01), whereas 10/17 in control, and 6/14 in levonorgestrel, groups attached. The attachment was confirmed by the positive expression of cytokeratin 7 at the attachment site. CONCLUSION: Mifepristone inhibits blastocyst attachment. Levonorgestrel did not impair the attachment of human embryos to the in vitro endometrial construct. This model could be used to understand endometrial receptivity and embryo-endometrial dialog and to develop new fertility regulating substances.
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- Rashid, NA, et al.
(författare)
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Endometrial receptivity and human embryo implantation
- 2011
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Ingår i: American journal of reproductive immunology (New York, N.Y. : 1989). - : Wiley. - 1600-0897 .- 1046-7408. ; 6666 Suppl 1, s. 23-30
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Tidskriftsartikel (refereegranskat)
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| 12. |
- Altmae, S, et al.
(författare)
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Meta-signature of human endometrial receptivity: a meta-analysis and validation study of transcriptomic biomarkers
- 2017
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 10077-
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Tidskriftsartikel (refereegranskat)abstract
- Previous transcriptome studies of the human endometrium have revealed hundreds of simultaneously up- and down-regulated genes that are involved in endometrial receptivity. However, the overlap between the studies is relatively small, and we are still searching for potential diagnostic biomarkers. Here we perform a meta-analysis of endometrial-receptivity associated genes on 164 endometrial samples (76 from ‘pre-receptive’ and 88 from mid-secretory, ‘receptive’ phase endometria) using a robust rank aggregation (RRA) method, followed by enrichment analysis, and regulatory microRNA prediction. We identify a meta-signature of endometrial receptivity involving 57 mRNA genes as putative receptivity markers, where 39 of these we confirm experimentally using RNA-sequencing method in two separate datasets. The meta-signature genes highlight the importance of immune responses, the complement cascade pathway and the involvement of exosomes in mid-secretory endometrial functions. Bioinformatic prediction identifies 348 microRNAs that could regulate 30 endometrial-receptivity associated genes, and we confirm experimentally the decreased expression of 19 microRNAs with 11 corresponding up-regulated meta-signature genes in our validation experiments. The 57 identified meta-signature genes and involved pathways, together with their regulatory microRNAs could serve as promising and sought-after biomarkers of endometrial receptivity, fertility and infertility.
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| 24. |
- Lalitkumar, S, et al.
(författare)
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Mid-trimester induced abortion: a review
- 2007
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Ingår i: Human reproduction update. - : Oxford University Press (OUP). - 1355-4786 .- 1460-2369. ; 13:1, s. 37-52
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Tidskriftsartikel (refereegranskat)
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- Stewart, EA, et al.
(författare)
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Uterine fibroids
- 2016
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Ingår i: Nature reviews. Disease primers. - : Springer Science and Business Media LLC. - 2056-676X. ; 2, s. 16043-
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Tidskriftsartikel (refereegranskat)
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| 29. |
- Tang, YQ, et al.
(författare)
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Bromocriptine inhibits proliferation in the endometrium from women with adenomyosis
- 2023
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Ingår i: Frontiers in endocrinology. - : Frontiers Media SA. - 1664-2392. ; 14, s. 1026168-
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Tidskriftsartikel (refereegranskat)abstract
- 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.MethodsEndometrial 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.ResultsVaginal 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.ConclusionBromocriptine 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.
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