Brosens, JJ and Hodgetts, A and Feroze-Zaidi, F and Sherwin, JRA and Fusi, L and Salker, MS and Higham, J and Rose, GL and Kajihara, T and Young, SL and Lessey, BA and Henriet, P and Langford, PR and Fazleabas, AT (2010) Proteomic analysis of endometrium from fertile and infertile patients suggests a role for apolipoprotein A-I in embryo implantation failure and endometriosis. MOL HUM REPROD , 16 (4) 273 - 285. 10.1093/molehr/gap108.
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Pregnancy is dependent upon the endometrium acquiring a receptive phenotype that facilitates apposition, adhesion and invasion of a developmentally competent embryo. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry of mid-secretory endometrial biopsies revealed a 28 kDa protein peak that discriminated highly between samples obtained from women with recurrent implantation failure and fertile controls. Subsequent tandem mass spectroscopy unambiguously identified this peak as apolipoprotein A-I (apoA-I), a potent anti-inflammatory molecule. Total endometrial apoA-I levels were, however, comparable between the study and control group. Moreover, endometrial apoA-I mRNA expression was not cycle-dependent although there was partial loss of apoA-I immunoreactivity in luminal and glandular epithelium in mid-secretory compared with proliferative endometrial samples. Because of its putative anti-implantation properties, we examined whether endometrial apoA-I expression is regulated by embryonic signals. Human chorionic gonadotrophin (hCG) strongly inhibited apoA-I expression in differentiating explant cultures but not when established from eutopic endometrium from patients with endometriosis. Pelvic endometriosis was associated with elevated apoA-I mRNA levels, increased secretion by differentiating eutopic endometrial explant cultures and lack of hCG-dependent down-regulation. To corroborate these observations, we examined endometrial apoA-I expression and its regulation by hCG in a non-human primate model of endometriosis. As in humans, hCG strongly inhibited endometrial apoA-I mRNA expression in disease-free baboons, but this response was entirely lost upon induction of pelvic endometriosis. Together, these observations indicate that perturbations in endometrial apoA-I expression, modification or regulation by paracrine embryonic signals play a major role in implantation failure and infertility.
|Title:||Proteomic analysis of endometrium from fertile and infertile patients suggests a role for apolipoprotein A-I in embryo implantation failure and endometriosis|
|Keywords:||apolipoprotein A-I, endometrium, endometriosis implantation, infertility, proteomics, HUMAN CHORIONIC-GONADOTROPIN, LEUKEMIA INHIBITORY FACTOR, GENE-EXPRESSION, STROMAL CELLS, GEL-ELECTROPHORESIS, UTERINE RECEPTIVITY, MASS-SPECTROMETRY, PERITONEAL-FLUID, CANDIDATE GENES, WOMEN|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology > Molecular Neuroscience|
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