Prostaglandin pathway gene expression in human placenta, amnion and choriodecidua is differentially affected by preterm and term labour and by uterine inflammation

Phillips, Robert; Fortier, Michel A.; Bernal, Andrés López

doi:10.1186/1471-2393-14-241

Cited by 61 publications

(42 citation statements)

References 51 publications

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“…Among other key enzymes of prostaglandin synthesis, PTGES , involved in PGF 2 synthesis, was elevated in the amnion in TIL cases [148]. The same study found increased expression levels of AKR1C3 (aldo-keto reductase), involved in PGF 2α synthesis, in the choriodecidua in TIL cases [148].…”

Section: Discussionmentioning

confidence: 97%

Characteristic Changes in Decidual Gene Expression Signature in Spontaneous Term Parturition

Elazzamy

Balogh

Romero

et al. 2017

J Pathol Transl Med

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BackgroundThe decidua has been implicated in the “terminal pathway” of human term parturition, which is characterized by the activation of pro-inflammatory pathways in gestational tissues. However, the transcriptomic changes in the decidua leading to terminal pathway activation have not been systematically explored. This study aimed to compare the decidual expression of developmental signaling and inflammation-related genes before and after spontaneous term labor in order to reveal their involvement in this process. MethodsChorioamniotic membranes were obtained from normal pregnant women who delivered at term with spontaneous labor (TIL, n = 14) or without labor (TNL, n = 15). Decidual cells were isolated from snap-frozen chorioamniotic membranes with laser microdissection. The expression of 46 genes involved in decidual development, sex steroid and prostaglandin signaling, as well as pro- and anti-inflammatory pathways, was analyzed using high-throughput quantitative real-time polymerase chain reaction (qRT-PCR). Chorioamniotic membrane sections were immunostained and then semi-quantified for five proteins, and immunoassays for three chemokines were performed on maternal plasma samples. ResultsThe genes with the highest expression in the decidua at term gestation included insulin-like growth factor-binding protein 1 (IGFBP1), galectin-1 (LGALS1), and progestogen-associated endometrial protein (PAEP); the expression of estrogen receptor 1 (ESR1), homeobox A11 (HOXA11), interleukin 1β (IL1B), IL8, progesterone receptor membrane component 2 (PGRMC2), and prostaglandin E synthase (PTGES) was higher in TIL than in TNL cases; the expression of chemokine C-C motif ligand 2 (CCL2), CCL5, LGALS1, LGALS3, and PAEP was lower in TIL than in TNL cases; immunostaining confirmed qRT-PCR data for IL-8, CCL2, galectin-1, galectin-3, and PAEP; and no correlations between the decidual gene expression and the maternal plasma protein concentrations of CCL2, CCL5, and IL-8 were found. ConclusionsOur data suggests that with the initiation of parturition, the decidual expression of anti-inflammatory mediators decreases, while the expression of pro-inflammatory mediators and steroid receptors increases. This shift may affect downstream signaling pathways that can lead to parturition.

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Section: Discussionmentioning

confidence: 97%

Characteristic Changes in Decidual Gene Expression Signature in Spontaneous Term Parturition

Elazzamy

Balogh

Romero

et al. 2017

J Pathol Transl Med

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“…We demonstrated that the inflammatory marker IL-6 is upregulated in labored placentas, collected from women with vaginal delivery, compared to placentas from women who underwent elective cesarean section. Phillips et al, demonstrated a negative correlation between inflammatory prostaglandins synthetic enzymes expression and the duration of labor in term and preterm gestations, suggesting that transcriptionally regulation of inflammatory related genes affects parturition in terms of prolonged stressful labor (Phillips et al, 2014). In agreement with the hypothesis of an acute and self resolving inflammation characterizing the physiology of labor, we showed that IL-6 cytokine expression inversely correlates with labor duration, ranging from 1 h to 10 h. This observation suggests that a robust inflammatory mediators release facilitates the expulsion of a viable offspring.…”

Section: Discussionmentioning

confidence: 99%

De novo ceramide synthesis is involved in acute inflammation during labor

Signorelli

Avagliano

Reforgiato

et al. 2016

Biological Chemistry

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Gestation is regulated by an inflammatory process that allows implantation and parturition. The comprehension of such inflammatory switches is important for the identification of therapeutic targets in pregnancy defects. Sphingolipids are a class of structural membrane components with important signaling functions. Among sphingolipids, ceramide is a well-known mediator of stress signals and pro-inflammatory responses. In this paper, we evaluated the association between ceramide increase and the inflammatory process of labor, comparing placentas from vaginal deliveries, including both spontaneous and induced labor, versus elective cesarean. We demonstrated that: (i) the inflammatory marker IL-6 is upregulated in labored placentas; (ii) IL-6 content inversely correlates with labor duration; (iii) ceramide content and expression of serine palmitoyl transferase (SPT, rate limiting enzyme for de novo ceramide synthesis) are increased in labored placentas; (iv) the expression of SPT directly correlates with inflammation and inversely with labor duration. These observations suggest that ceramide metabolism and signaling may be implicated in controlling important inflammatory mechanisms driving gestation: we hypothesize that ceramide can be a therapeutic target in inflammatory complications of parturition.

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“…Placental expression of 17β-HSD3, which is involved in testosterone formation, is increased in preeclamptic women ( Shao et al, 2017 ). 17β-HSD5 protein ( Phillips et al, 2014 ) and 17β-HSD7 mRNA ( Krazeisen et al, 1999 ) expression were shown in human placenta.…”

Section: Steroid Hormonesmentioning

confidence: 99%

Physiology and Pathophysiology of Steroid Biosynthesis, Transport and Metabolism in the Human Placenta

2018

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The steroid hormones progestagens, estrogens, androgens, and glucocorticoids as well as their precursor cholesterol are required for successful establishment and maintenance of pregnancy and proper development of the fetus. The human placenta forms at the interface of maternal and fetal circulation. It participates in biosynthesis and metabolism of steroids as well as their regulated exchange between maternal and fetal compartment. This review outlines the mechanisms of human placental handling of steroid compounds. Cholesterol is transported from mother to offspring involving lipoprotein receptors such as low-density lipoprotein receptor (LDLR) and scavenger receptor class B type I (SRB1) as well as ATP-binding cassette (ABC)-transporters, ABCA1 and ABCG1. Additionally, cholesterol is also a precursor for placental progesterone and estrogen synthesis. Hormone synthesis is predominantly performed by members of the cytochrome P-450 (CYP) enzyme family including CYP11A1 or CYP19A1 and hydroxysteroid dehydrogenases (HSDs) such as 3β-HSD and 17β-HSD. Placental estrogen synthesis requires delivery of sulfate-conjugated precursor molecules from fetal and maternal serum. Placental uptake of these precursors is mediated by members of the solute carrier (SLC) family including sodium-dependent organic anion transporter (SOAT), organic anion transporter 4 (OAT4), and organic anion transporting polypeptide 2B1 (OATP2B1). Maternal–fetal glucocorticoid transport has to be tightly regulated in order to ensure healthy fetal growth and development. For that purpose, the placenta expresses the enzymes 11β-HSD 1 and 2 as well as the transporter ABCB1. This article also summarizes the impact of diverse compounds and diseases on the expression level and activity of the involved transporters, receptors, and metabolizing enzymes and concludes that the regulatory mechanisms changing the physiological to a pathophysiological state are barely explored. The structure and the cellular composition of the human placental barrier are introduced. While steroid production, metabolism and transport in the placental syncytiotrophoblast have been explored for decades, few information is available for the role of placental-fetal endothelial cells in these processes. With regard to placental structure and function, significant differences exist between species. To further decipher physiologic pathways and their pathologic alterations in placental steroid handling, proper model systems are mandatory.

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Prostaglandin pathway gene expression in human placenta, amnion and choriodecidua is differentially affected by preterm and term labour and by uterine inflammation

Cited by 61 publications

References 51 publications

Characteristic Changes in Decidual Gene Expression Signature in Spontaneous Term Parturition

Characteristic Changes in Decidual Gene Expression Signature in Spontaneous Term Parturition

De novo ceramide synthesis is involved in acute inflammation during labor

Physiology and Pathophysiology of Steroid Biosynthesis, Transport and Metabolism in the Human Placenta

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