Results
| PMID | 20008415 |
| Gene Name | APOA1 |
| Condition | Endometriosis |
| Association |
Associated |
| Sex | Female |
| Infertility type | Female infertility |
| Associated genes | apoA-I |
| Other associated phenotypes |
Endometriosis |
|
Mol Hum Reprod. 2010 Apr;16(4):273-85. doi: 10.1093/molehr/gap108. Epub 2009 Dec Brosens, Jan J| Hodgetts, Andrea| Feroze-Zaidi, Fahkera| Sherwin, J Robert A| Fusi, Luca| Salker, Madhuri S| Higham, Jenny| Rose, Gillian L| Kajihara, Takeshi| Young, Steven L| Lessey, Bruce A| Henriet, Patrick| Langford, Paul R| Fazleabas, A Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 ONN, UK. j.brosens@imperial.ac.uk 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. Mesh Terms: Adult| Animals| Apolipoprotein A-I/*metabolism| Blotting, Western| Cells, Cultured| Embryo Implantation/*physiology| Endometriosis/*metabolism| Endometrium/*metabolism| Enzyme-Linked Immunosorbent Assay| Female| Humans| Immunohistochemistry| I |
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