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

Brosens, Jan J.;Hodgetts, Andrea;Feroze-Zaidi, Fahkera;Sherwin, J. Robert A.;Fazleabas, Asgerally T.;et.al.
(2010) Molecular Human Reproduction : basic science of reproductive medicine — Vol. 16, n° 4, p. 273-285 (2010)

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Authors
  • Brosens, Jan J.
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  • Hodgetts, Andrea
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  • Feroze-Zaidi, Fahkera
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  • Sherwin, J. Robert A.
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  • Henriet, PatrickUCLouvain
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  • Fazleabas, Asgerally T.
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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.
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Brosens, J. J., Hodgetts, A., Feroze-Zaidi, F., Sherwin, J. R. A., Fusi, L., Salker, M. S., Higham, J., Rose, G. L., Kajihara, T., Young, S. L., Lessey, B. A., Henriet, P., Langford, P. R., & Fazleabas, A. T. (2010). Proteomic analysis of endometrium from fertile and infertile patients suggests a role for apolipoprotein A-I in embryo implantation failure and endometriosis. Molecular Human Reproduction : basic science of reproductive medicine, 16(4), 273-285. https://doi.org/10.1093/molehr/gap108 (Original work published 2010)