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2 results on '"decidualization resistance"'

1. Decidualization resistance in the origin of preeclampsia.

Author

Garrido-Gómez, Tamara, Castillo-Marco, Nerea, Cordero, Teresa, and Simón, Carlos

Subjects
PREECLAMPSIA, KILLER cells, UTERINE hemorrhage, HELLP syndrome, MENSTRUAL cycle, MOTHER-child relationship
Abstract

Preeclampsia is a major obstetrical complication with short- and long-term life-threatening consequences for both mother and child. Shallow cytotrophoblast invasion through the uterine decidua into the spiral arteries is implicated in the pathogenesis of preeclampsia, although the cause of deficient arterial invasion remains unknown. Research that is focused on the "soil"-the maternal decidua-highlights the importance of this poorly understood but influential uterine layer. Decidualization of endometrial cells regulates embryo invasion, which is essential for spiral artery remodeling and establishing the maternal-fetal interface. Exploration of the association between impaired decidualization and preeclampsia revealed suboptimal endometrial maturation and uterine natural killer cells present in the decidua before preeclampsia development. Furthermore, decidualization defects in the endometrium of women with severe preeclampsia, characterized by impaired cytotrophoblast invasion, were detected at the time of delivery and persisted 5 years after the affected pregnancy. Recently, a maternal deficiency of annexin A2 expression was found to influence aberrant decidualization and shallow cytotrophoblast invasion, suggesting that decidualization resistance, which is a defective endometrial cell differentiation during the menstrual cycle, could underlie shallow trophoblast invasion and the poor establishment of the maternal-fetal interface. Based on these findings, the transcriptional signature in the endometrium that promotes decidualization deficiency could be detected before (or after) conception. This would serve to identify women at risk of developing severe preeclampsia and aid the development of therapies focused on improving decidualization, perhaps also preventing severe preeclampsia. Here, we discuss decidualization deficiency as a contributor to the pathogenesis of pregnancy disorders with particular attention to severe preeclampsia. We also review current diagnostic strategies and discuss future directions in diagnostic methods based on decidualization. [ABSTRACT FROM AUTHOR]

Published
2022
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2. Preeclampsia: a defect in decidualization is associated with deficiency of Annexin A2

Author

Garrido-Gomez T, Quinonero A, Dominguez F, Rubert L, Perales A, Hajjar K, and Simon C

Subjects
human endometrial stromal cells, ANXA2 deficiency, ANXA2-null mice, decidualization resistance, human endometrial stromal cells, placentation defect, severe preeclampsia, decidualization resistance, placentation, severe preeclampsia, ANXA2 deficiency, ANXA2-null mice
Abstract

BACKGROUND: Decidualization defects in the endometrium have been demonstrated at the time of delivery in women with severe preeclampsia (sPE) and linger for years, suggesting a maternal contribution to the pathogenesis of this condition. Global transcriptional profiling reveals alterations in gene expression, including downregulation of Annexin A2 (ANXA2) in sPE patients with decidualization resistance.; OBJECTIVE: We investigated the functional role of ANXA2 deficiency during endometrial decidualization and its potential contribution to shallow trophoblast invasion during implantation and subsequent placentation using in vitro and in vivo modeling.; STUDY DESIGN: ANXA2 gene and protein levels were assessed during in vitro decidualization of human endometrial stromal cells (hESCs) isolated from biopsies collected from women with previous severe preeclampsia (sPE) (n=5) or normal obstetric outcomes (n=5). Next, ANXA2 was inhibited with small interference RNA (siRNA) in control hESC cells isolated from endometrial biopsies (n=15) as an in vitro model to analyze decidualization defects at the morphological level as well as secretion of prolactin (PRL) and insulin-like growth binding protein-1 (IGFPB1). ANXA2-inhibited cells were used to evaluate motility and promotion of embryo invasion. Decidualization and placentation defects of ANXA2 deficiency were confirmed using an ANXA2-null mouse model.; RESULTS: ANXA2 gene and protein levels were downregulated during in vitro decidualization of hESCs from women with prior sPE compared to control individuals. To assess its role in the endometrial stroma, we inhibited ANXA2 expression and detected decidualization failure as evidenced by impaired morphological transformation, which was associated with altered actin polymerization and low PRL and IGFBP1 secretions. Functionally, in vitro models demonstrated that ANXA2 inhibition failed to support embryo invasion. This finding was corroborated by reduced trophoblast spreading through hESCs, lack of motility of these cells, and reduced trophoblast invasion in the presence of conditioned media from ANXA2-inhibited cells. Extending our discovery to an animal model, we detected that ANXA2-null mice have a functional deficiency in decidualization and placentation that impairs fetal growth as a feature associated with sPE.; CONCLUSIONS: Together, in vitro and in vivo results suggest that endometrial defects in ANXA2 expression impair decidualization of endometrial stromal cells as well as the uterine microenvironment that promotes embryo implantation and placentation. Our findings highlight the maternal contribution to the pathogenesis of sPE and suggest that evaluation of ANXA2 may provide a novel strategy to assess a woman's risk of developing this pathology and perhaps discover therapeutic interventions to improve decidualization. Copyright © 2019 Elsevier Inc. All rights reserved.

Published
2020

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