Aberrant retinoic acid production in the decidua: Implications for pre-eclampsia

• Type of Material: Article
• Authors: Augustine Rajakumar, Emory University; Maureen A Kane, University of Maryland, Baltimore; Jie Yu, Wake Forest School of Medicine; Robert N Taylor, University of Utah; Neil Sidell, Emory University
• Language: English
• Date: 2020-04-28
• Publisher: WILEY
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2020 Japan Society of Obstetrics and Gynecology
• Final Published Version (URL): http://dx.doi.org/10.1111/jog.14262
• Title of Journal or Parent Work: JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH
• Volume: 46
• Issue: 7
• Start Page: 1007
• End Page: 1016
• Keywords: UP-REGULATION; preeclampsia; ANGIOGENIC FACTORS; EARLY-PREGNANCY; VITAMIN-A; TRANSCRIPTIONAL REGULATION; ENDOMETRIAL STROMAL CELLS; retinoic acid; decidualization; BINDING-PROTEIN; Obstetrics & Gynecology; ENDOTHELIAL GROWTH-FACTOR; Science & Technology; INTERCELLULAR COMMUNICATION; fms-like tyrosine kinase-1; Life Sciences & Biomedicine; Cx43; DENDRITIC CELLS

Abstract

Fine-tuning of the endometrium during the evanescent ‘window of implantation’ relies upon an array of diverse and redundant signaling molecules, particularly the ovarian steroids E2 and P4, but also growth factors, eicosanoids, and vitamins including the vitamin A compounds (retinoids). Pregnancy complications such as preeclampsia (PE) can result from aberrations in the production or function of these molecules that arise during this critical period of decidual development. Such aberrations may be reflected by incomplete decidualization, reduced spiral artery modification, and/or loss of immune tolerance to the developing fetus. Our understanding of the role of the active retinoid metabolite all-trans retinoic acid (RA) in maintaining immune balance in certain tissues, along with data describing its role in decidualization, present a compelling argument that aberrant RA signaling in the decidua can play a significant role in the etiology of PE. Recent findings that decidualization and expression of the anti-angiogenic gene product, ‘soluble fms-like tyrosine kinase-1’ (sFLT1) are negatively correlated and that sFLT1 expression is directly inhibited by RA, provide additional evidence of the critical role of this retinoid in regulating early vascular development in the decidua. This review provides insight into the production and function of RA in the decidua and how modifications in its metabolism and signaling might lead to certain pregnancy disorders such as PE.