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Title: | Assessment of potential biomarkers of pre-receptive and receptive endometrium in uterine fluid and a functional evaluation of the potential role of CSF3 in fertility. | Authors: | Vollenhoven B.J. ;Salamonsen L.A.;Edgell T.A.;Evans J.;Lazzaro L.;Boyes K.;Sridhar M.;Catt S.;Rombauts L.J.F. | Monash Health Department(s): | Obstetrics and Gynaecology (Monash Women's) | Institution: | (Edgell, Evans, Rombauts, Vollenhoven, Salamonsen) Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, Australia (Edgell, Evans, Salamonsen) Department of Molecular and Translational Science, Monash University, Clayton, Australia (Lazzaro, Boyes, Sridhar, Catt, Rombauts, Vollenhoven) Department of Obstetrics and Gynaecology, Monash University, Clayton, Australia (Rombauts, Vollenhoven) Monash IVF, Clayton, Australia (Rombauts, Vollenhoven) Women's and New Born Programme, Monash Health, Clayton, Australia | Issue Date: | 15-Sep-2018 | Copyright year: | 2018 | Publisher: | Academic Press | Place of publication: | United Kingdom | Publication information: | Cytokine. 111 (pp 222-229), 2018. Date of Publication: November 2018. | Journal: | Cytokine | Abstract: | The endometrium lines a women's uterus becoming receptive, and allowing embryo implantation to occur, for just a few days during the post-ovulatory mid-secretory phase of each menstrual cycle. We investigated whether concentrations of proposed receptivity biomarkers (VEGF, IL8, FGF2, CSF3 sFlt-1, sGP130 and PlGF) secreted by the endometrium into the uterine cavity and forming the microenvironment for embryo implantation is altered among a population of age-matched women with unexplained (idiopathic) infertility compared to fertile women during the receptive mid-secretory phase (n = 16 fertile, 18 infertile) and the prior pre-receptive early secretory phase (n = 19 fertile, 18 infertile) of their cycle. In the mid-secretory cohort significantly elevated concentrations of five biomarkers; PlGF (p = 0.001), IL8 (p = 0.004), sGP130 (p = 0.009), sFlt-1 (p = 0.021), and CSF3 (p = 0.029) was present in uterine fluid of infertile women during the mid-secretory phase, but only CSF3 was significantly elevated in the pre-receptive early secretory phase (p = 0.006). In vitro studies of glycosylated and non-glycosylated forms of CSF3 at representative fertile (20 ng/mL) and infertile (70 ng/mL) effects on endometrium and embryo behaviour were performed. Non-glycosylated CSF3 at fertile concentrations significantly (p < 0.001) elevated endometrial epithelial cell proliferation however chronic treatment or elevated (infertile) concentrations of CSF3 in glycosylated form abrogated the positive effects. Both forms of CSF3 increased trophoblast cell invasion (p < 0.001) regardless of concentration. Mouse embryo outgrowth was significantly (p < 0.01) increased at fertile but not at infertile concentrations. The study confirmed potential utility of five biomarkers of endometrial receptivity for future application in the mid-secretory phase while highlighting CSF3 is elevated in the earlier pre-receptive phase. Our data provides evidence that CSF3 acts on both human endometrium and embryo in a manner that is concentration and glycosylation dependent.Copyright © 2018 Elsevier Ltd | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1016/j.cyto.2018.08.026 | Link to associated publication: | Click here for full text options | PubMed URL: | 30195213 [http://www.ncbi.nlm.nih.gov/pubmed/?term=30195213] | ISSN: | 1043-4666 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/37178 | Type: | Article | Subjects: | protein glycosylation protein secretion uterus cavity *uterus fluid *biological marker/ec [Endogenous Compound] *colony stimulating factor/ec [Endogenous Compound] *fibroblast growth factor 2/ec [Endogenous Compound] *glycoprotein gp 130/ec [Endogenous Compound] *interleukin 8/ec [Endogenous Compound] *placental growth factor/ec [Endogenous Compound] unclassified drug *vasculotropin/ec [Endogenous Compound] *vasculotropin receptor 1/ec [Endogenous Compound] *colony stimulating factor 3/ec [Endogenous Compound] nonhuman adult age animal tissue article cell proliferation cohort analysis controlled study embryo embryo growth *endometrium female *female fertility female infertility human human tissue idiopathic disease menstrual cycle mouse nidation priority journal *protein function human cell proliferation idiopathic disease menstrual cycle mouse nidation nonhuman priority journal *protein function protein glycosylation protein secretion uterus cavity *uterus fluid Article animal tissue age adult human tissue cohort analysis controlled study embryo embryo growth *endometrium female *female fertility female infertility |
Type of Clinical Study or Trial: | Observational study (cohort, case-control, cross sectional or survey) |
Appears in Collections: | Articles |
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