title: Proteomic analysis of endometrium from fertile and infertile patients suggests a role for apolipoprotein A-I in embryo implantation failure and endometriosis.
abstract: 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.
authors.affiliation: Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK. j.brosens@imperial.ac.uk
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Brosens
authors.forename: Andrea
authors.initials: A
authors.lastname: Hodgetts
authors.forename: Fahkera
authors.initials: F
authors.lastname: Feroze-Zaidi
authors.forename: J Robert A
authors.initials: JR
authors.lastname: Sherwin
authors.forename: Luca
authors.initials: L
authors.lastname: Fusi
authors.forename: Madhuri S
authors.initials: MS
authors.lastname: Salker
authors.forename: Jenny
authors.initials: J
authors.lastname: Higham
authors.forename: Gillian L
authors.initials: GL
authors.lastname: Rose
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kajihara
authors.forename: Steven L
authors.initials: SL
authors.lastname: Young
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Lessey
authors.forename: Patrick
authors.initials: P
authors.lastname: Henriet
authors.forename: Paul R
authors.initials: PR
authors.lastname: Langford
authors.forename: Asgerally T
authors.initials: AT
authors.lastname: Fazleabas
mesh_terms: D000328:Adult; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D010064:Embryo Implantation / Q000502:physiology*; D004715:Endometriosis / Q000378:metabolism*; D004717:Endometrium / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007247:Infertility, Female / Q000378:metabolism*; D013058:Mass Spectrometry; D010215:Papio; D011247:Pregnancy
chemical_list: D016632:Apolipoprotein A-I