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

Publication ,  Journal Article
Brosens, JJ; Hodgetts, A; Feroze-Zaidi, F; Sherwin, JRA; Fusi, L; Salker, MS; Higham, J; Rose, GL; Kajihara, T; Young, SL; Lessey, BA ...
Published in: Mol Hum Reprod
April 2010

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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Published In

Mol Hum Reprod

DOI

EISSN

1460-2407

Publication Date

April 2010

Volume

16

Issue

4

Start / End Page

273 / 285

Location

England

Related Subject Headings

  • Pregnancy
  • Papio
  • Obstetrics & Reproductive Medicine
  • Mass Spectrometry
  • Infertility, Female
  • Immunohistochemistry
  • Humans
  • Female
  • Enzyme-Linked Immunosorbent Assay
  • Endometrium
 

Citation

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Brosens, J. J., Hodgetts, A., Feroze-Zaidi, F., Sherwin, J. R. A., Fusi, L., Salker, M. S., … 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. Mol Hum Reprod, 16(4), 273–285. https://doi.org/10.1093/molehr/gap108
Brosens, Jan J., Andrea Hodgetts, Fahkera Feroze-Zaidi, J Robert A. Sherwin, Luca Fusi, Madhuri S. Salker, Jenny Higham, et al. “Proteomic analysis of endometrium from fertile and infertile patients suggests a role for apolipoprotein A-I in embryo implantation failure and endometriosis.Mol Hum Reprod 16, no. 4 (April 2010): 273–85. https://doi.org/10.1093/molehr/gap108.
Brosens JJ, Hodgetts A, Feroze-Zaidi F, Sherwin JRA, Fusi L, Salker MS, et al. Proteomic analysis of endometrium from fertile and infertile patients suggests a role for apolipoprotein A-I in embryo implantation failure and endometriosis. Mol Hum Reprod. 2010 Apr;16(4):273–85.
Brosens, Jan J., et al. “Proteomic analysis of endometrium from fertile and infertile patients suggests a role for apolipoprotein A-I in embryo implantation failure and endometriosis.Mol Hum Reprod, vol. 16, no. 4, Apr. 2010, pp. 273–85. Pubmed, doi:10.1093/molehr/gap108.
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. Proteomic analysis of endometrium from fertile and infertile patients suggests a role for apolipoprotein A-I in embryo implantation failure and endometriosis. Mol Hum Reprod. 2010 Apr;16(4):273–285.
Journal cover image

Published In

Mol Hum Reprod

DOI

EISSN

1460-2407

Publication Date

April 2010

Volume

16

Issue

4

Start / End Page

273 / 285

Location

England

Related Subject Headings

  • Pregnancy
  • Papio
  • Obstetrics & Reproductive Medicine
  • Mass Spectrometry
  • Infertility, Female
  • Immunohistochemistry
  • Humans
  • Female
  • Enzyme-Linked Immunosorbent Assay
  • Endometrium