Progesterone Resistance in Endometriosis Is Modulated by the Altered Expression of MicroRNA-29c and FKBP4

Niraj R Joshi, Niraj Joshi, Eduardo H Miyadahira, Miyadahira EH, Eduardo Hideki Miyadahira, Yalda Afshar, Jae-Wook Jeong, Jae‐Wook Jeong, Jeong JW, Steven L. Young, Lessey BA, Bruce A. Lessey, Paulo C Serafini, P. Serafini, Serafini Pc, Asgerally T Fazleabas, Fazleabas AT
The Journal of clinical endocrinology and metabolism · 2016 · vol. 102(1) , pp. jc.2016–2076 · doi:10.1210/jc.2016-2076 · PMID:27778641 · PMC5413101 · W2534032587
Lab / animal OA: bronze CC0 ⤵ 62 in-corpus citations
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Increased miR-29c expression in endometriosis endometrium reduces FKBP4 levels, potentially causing progesterone resistance, and this effect is reversed by surgical endometriosis resection.

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Abstract

CONTEXT: Endometriosis results in aberrant gene expression in the eutopic endometrium (EuE) and subsequent progesterone resistance. MicroRNA (miR) microarray data in a baboon model of endometriosis showed an increased expression of miR-29c. OBJECTIVES: To explore the role of miR-29c in progesterone resistance in a subset of women with endometriosis. DESIGN: MiR-29c expression was analyzed in the endometrium of baboons and women with or without endometriosis. The role in progesterone resistance and decidualization was analyzed by transfecting human uterine fibroblast cells with miR-29c. PATIENTS: Subjects diagnosed with deep infiltrative endometriosis (DIE) by transvaginal ultrasound with bowel preparation underwent surgical excision of endometriosis. Eutopic secretory endometrium was collected pre- and postoperatively. Women with normal EuE and without DIE served as controls. RESULTS: Quantitative reverse transcription polymerase chain reaction demonstrated that miR-29c expression increased, while the transcript levels of its target, FK506-binding protein 4 (FKBP4), decreased in the EuE of baboons following the induction of endometriosis. FKBP4 messenger RNA and decidual markers were statistically significantly decreased in decidualized human uterine fibroblast cells transfected with a miR-29c mimic compared with controls. Human data corroborated our baboon data and demonstrated higher expression of miR-29c in endometriosis EuE compared with normal EuE. MiR-29c was significantly decreased in endometriosis EuE postoperatively compared with preoperative tissues, and FKBP4 showed an inverse trend following radical laparoscopic resection surgery. CONCLUSIONS: We demonstrate that miR-29c expression is increased in EuE of baboons and women with endometriosis, which might contribute to a compromised progesterone response by diminishing the levels of FKBP4. Resection of DIE is likely to reverse the progesterone resistance associated with endometriosis in women.

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Condition tags

endometriosisdie_deep_infiltrating

MeSH descriptors

Biomarkers Endometriosis Endometrium MicroRNAs Progesterone Tacrolimus Binding Proteins Uterine Diseases Animals Animals Biomarkers Biomarkers Case-Control Studies Case-Control Studies Disease Models, Animal Disease Models, Animal Endometriosis Endometriosis Endometriosis Endometriosis Endometrium

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Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

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