Proteomic analysis of endometrium from fertile and infertile patients suggests a role for apolipoprotein A-I in embryo implantation failure and endometriosis.
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.
Brosens
Jan J
JJ
Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK. j.brosens@imperial.ac.uk
Hodgetts
Andrea
A
Feroze-Zaidi
Fahkera
F
Sherwin
J Robert A
JR
Fusi
Luca
L
Salker
Madhuri S
MS
Higham
Jenny
J
Rose
Gillian L
GL
Kajihara
Takeshi
T
Young
Steven L
SL
Lessey
Bruce A
BA
Henriet
Patrick
P
Langford
Paul R
PR
Fazleabas
Asgerally T
AT
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
D016632:Apolipoprotein A-I