Proteomic analysis of endometrium from fertile and infertile patients suggests a role for apolipoprotein A-I in embryo implantation failure and endometriosis

被引：48

作者：

Brosens, Jan J. ^{[1
]}

Hodgetts, Andrea

Feroze-Zaidi, Fahkera ^{[1
]}

Sherwin, J. Robert A. ^{[2
]}

Fusi, Luca ^{[1
]}

Salker, Madhuri S. ^{[1
]}

Higham, Jenny ^{[1
]}

Rose, Gillian L. ^{[1
]}

Kajihara, Takeshi ^{[3
]}

Young, Steven L. ^{[4
]}

Lessey, Bruce A. ^{[5
]}

Henriet, Patrick ^{[6
]}

Langford, Paul R.

Fazleabas, Asgerally T. ^{[7
]}

机构：

[1] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Inst Reprod & Dev Biol, London W12 ONN, England

[2] Univ Cambridge, Rosie Hosp, Dept Obstet & Gynaecol, Cambridge, England

[3] Saitama Med Sch, Dept Obstet & Gynecol, Moroyama, Saitama 35004, Japan

[4] Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC USA

[5] Greenville Hosp Syst, Dept Obstet & Gynecol, Greenville, SC USA

[6] Univ Catholique Louvain, Cell Biol Unit, de Duve Inst, B-1200 Brussels, Belgium

[7] Univ Illinois, Coll Med, Dept Obstet & Gynecol, Chicago, IL 60612 USA

来源：

MOLECULAR HUMAN REPRODUCTION | 2010年 / 16卷 / 04期

关键词：

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;

D O I：

10.1093/molehr/gap108

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：273 / 285

页数：13