Proteomic analysis of endometrium from fertile and infertile patients suggests a role for apolipoprotein A-I in embryo implantation failure and endometriosis.
Journal Article (Journal Article)
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, JJ; Hodgetts, A; Feroze-Zaidi, F; Sherwin, JRA; Fusi, L; Salker, MS; Higham, J; Rose, GL; Kajihara, T; Young, SL; Lessey, BA; Henriet, P; Langford, PR; Fazleabas, AT
- April 2010
Volume / Issue
- 16 / 4
Start / End Page
- 273 - 285
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)
Digital Object Identifier (DOI)