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Sökning: WFRF:(Lalitkumar L)

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  • Altmae, S, et al. (författare)
  • Meta-signature of human endometrial receptivity: a meta-analysis and validation study of transcriptomic biomarkers
  • 2017
  • Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 7:1, s. 10077-
  • 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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  • Lalitkumar, P. G. L, et al. (författare)
  • Mifepristone, but not levonorgestrel, inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model
  • 2007
  • Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 22:11, s. 3031-3037
  • 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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  • Hildenbrand, Anna, et al. (författare)
  • Aquaporin 1 is expressed in the human endometrium during normal cycle and increases after mifepristone treatment.
  • 2008
  • Ingår i: International Journal of Molecular Medicine. - 1107-3756 .- 1791-244X. ; 22:1, s. 49-53
  • Tidskriftsartikel (refereegranskat)abstract
    • Aquaporin-1 (AQP1) is involved in the angiogenesis and structural modifications of microvessels and possibly also in the pathogenesis of idiopathic menhorrhagia, where a reduced AQP1 expression is seen in the endometrium. Mifepristone treatment induces reduced menstrual bleeding and amenorrhea and also has a direct effect on endometrial arterioles. Administered with gestagen-only contraceptive methods, antiprogestins improve the bleeding pattern. The objective of this study was to evaluate the AQP1 expression in endometrial blood vessels during normal cycle and after mifepristone treatment. Localization and expression of AQP1 was determined using immunohistochemistry and reverse transcriptase chain reaction (RT-PCR) in 43 biopsies from human endometrium taken during a normal cycle and after mifepristone treatment. AQP1 expression in human endometrial vessels is not cycle dependent and is stronger in capillaries and arteries than in veins. After mifepristone treatment the staining intensity was increased, but not the number of stained vessels. The presence of AQP1 was also confirmed using RT-PCR. The changes in AQP1 expression could contribute to the reduced bleeding seen following mifepristone treatment and could be an effect of either antagonizing progesterone or cortisol.
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