{"doi":"10.17615/a3ra-g184","title":"Proteomic analysis of endometrium from fertile and infertile patients suggests a role for apolipoprotein A-I in embryo implantation failure and endometriosis","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.","journal":"UNC Libraries","year":2020,"id":110235,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9525,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":526042,"name":"A. Hodgetts","orcid":null,"position":1,"is_corresponding":false},{"id":526043,"name":"L. Fusi","orcid":null,"position":2,"is_corresponding":false},{"id":526044,"name":"J. J. Brosens","orcid":null,"position":3,"is_corresponding":false},{"id":393773,"name":"A.T. Fazleabas","orcid":null,"position":4,"is_corresponding":false},{"id":526045,"name":"J. Higham","orcid":null,"position":5,"is_corresponding":false},{"id":523400,"name":"B. A. Lessey","orcid":null,"position":6,"is_corresponding":false},{"id":399314,"name":"Steven L. Young","orcid":"0000-0002-5205-4495","position":7,"is_corresponding":false},{"id":526046,"name":"T. Kajihara","orcid":null,"position":8,"is_corresponding":false},{"id":525129,"name":"Patrick Henriet","orcid":"0000-0003-4602-8888","position":9,"is_corresponding":false},{"id":42699,"name":"Paul R. Langford","orcid":"0000-0002-6368-4724","position":10,"is_corresponding":false},{"id":526047,"name":"G. L. Rose","orcid":null,"position":11,"is_corresponding":false},{"id":526048,"name":"J. R. A. Sherwin","orcid":null,"position":12,"is_corresponding":false},{"id":525130,"name":"Madhuri S. Salker","orcid":"0000-0002-7939-289X","position":13,"is_corresponding":false},{"id":526041,"name":"F. Feroze-Zaidi","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:12:57.988348Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}