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Title: | Analysis of fertility-related soluble mediators in human uterine fluid identifies VEGF as a key regulator of embryo implantation. | Authors: | Salamonsen L.A.;Hannan N.J.;Paiva P.;Meehan K.L.;Rombauts L.J.F.;Gardner D.K. | Institution: | (Hannan, Paiva, Meehan, Salamonsen) Prince Henry's Institute of Medical Research, Monash University, Monash Medical Centre, Clayton, VIC 3168, Australia (Rombauts) Department of Obstetrics and Gynaecology, Monash University, Monash Medical Centre, Clayton, VIC 3168, Australia (Hannan, Gardner) Department of Zoology, University of Melbourne, Parkville, VIC 3010, Australia | Issue Date: | 9-Oct-2012 | Copyright year: | 2011 | Publisher: | Endocrine Society (8401 Connecticut Ave. Suite 900, Chevy Chase MD 20815, United States) | Place of publication: | United States | Publication information: | Endocrinology. 152 (12) (pp 4948-4956), 2011. Date of Publication: December 2011. | Abstract: | Embryo implantation requires synchronized dialogue between the receptive endometrium and activated blastocyst via locally produced soluble mediators. During the midsecretory (MS) phase of the menstrual cycle, increased glandular secretion into the uterine lumen contains important mediators that modulate the endometrium and support the conceptus during implantation. This study aimed first to identify the growth factor and cytokine profile of human uterine fluid from fertile women during the midproliferative (MP; nonreceptive) and MS (receptive) phases of the cycle, and from women with unexplained infertility during the MS phase. The second aim was to determine important functions of endometrial secretions for embryo implantation. Analysis of uterine fluid using quantitative Luminex assays revealed the presence of over 30 cytokines and growth factors, of which eight [platelet-derived growth factor-AA, TNF-B, soluble IL-2 receptor-A, Fms-like tyrosine kinase 3 ligand, soluble CD40 ligand, IL-7, interferon-A2, and chemokine (C-X-C motif) ligand 1-3] were previously unknown in human uterine fluid. Comparison of the fertile MP, MS, and infertile MS cohorts revealed vascular endothelial growth factor (VEGF) levels are significantly reduced in uterine fluid during the MS phase in women with unexplained infertility compared with fertile women. Functional studies demonstrated that culturing mouse embryos with either MS-phase uterine fluid from fertile women or recombinant human VEGF significantly enhanced blastocyst outgrowth. Furthermore, treatment of human endometrial epithelial cells with uterine fluid or recombinant human VEGF-A significantly increased endometrial epithelial cell adhesion. Taken together, our data support the concept that endometrial secretions, including VEGF, play important roles during implantation. Identifying the soluble mediators in human uterine fluid and their actions during implantation provides insight into interactions essential for establishing pregnancy, fertility markers, and infertility treatment options. Copyright © 2011 by The Endocrine Society. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1210/en.2011-1248 | PubMed URL: | 22028446 [http://www.ncbi.nlm.nih.gov/pubmed/?term=22028446] | ISSN: | 0013-7227 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/30312 | Type: | Article | Type of Clinical Study or Trial: | Observational study (cohort, case-control, cross sectional or survey) |
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