Role for the thromboxane A2 receptor β-isoform in the pathogenesis of intrauterine growth restriction

Katie L Powell, Veronica Stevens, Dannielle H Upton, Sharon A McCracken, Ann M Simpson, Yan Cheng, Vitomir Tasevski, Jonathan M Morris, Anthony W Ashton

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Abstract

Intrauterine growth restriction (IUGR) is a pathology of pregnancy that results in failure of the fetus to reach its genetically determined growth potential. In developed nations the most common cause of IUGR is impaired placentation resulting from poor trophoblast function, which reduces blood flow to the fetoplacental unit, promotes hypoxia and enhances production of bioactive lipids (TXA2 and isoprostanes) which act through the thromboxane receptor (TP). TP activation has been implicated as a pathogenic factor in pregnancy complications, including IUGR; however, the role of TP isoforms during pregnancy is poorly defined. We have determined that expression of the human-specific isoform of TP (TPβ) is increased in placentae from IUGR pregnancies, compared to healthy pregnancies. Overexpression of TPα enhanced trophoblast proliferation and syncytialisation. Conversely, TPβ attenuated these functions and inhibited migration. Expression of the TPβ transgene in mice resulted in growth restricted pups and placentae with poor syncytialisation and diminished growth characteristics. Together our data indicate that expression of TPα mediates normal placentation; however, TPβ impairs placentation, and promotes the development of IUGR, and represents an underappreciated pathogenic factor in humans.

Original languageEnglish
Article number28811
Pages (from-to)28811
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - 1 Jul 2016
Externally publishedYes

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Prostaglandin H2 Receptors Thromboxane A2
Protein Isoforms
Placentation
Growth
Pregnancy
Trophoblasts
Placenta
Thromboxane Receptors
Isoprostanes
Pregnancy Complications
Transgenes
Growth and Development
Developed Countries
Fetus
Pathology
Lipids

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Powell, K. L., Stevens, V., Upton, D. H., McCracken, S. A., Simpson, A. M., Cheng, Y., ... Ashton, A. W. (2016). Role for the thromboxane A2 receptor β-isoform in the pathogenesis of intrauterine growth restriction. Scientific Reports, 6, 28811. [28811]. https://doi.org/10.1038/srep28811
Powell, Katie L ; Stevens, Veronica ; Upton, Dannielle H ; McCracken, Sharon A ; Simpson, Ann M ; Cheng, Yan ; Tasevski, Vitomir ; Morris, Jonathan M ; Ashton, Anthony W. / Role for the thromboxane A2 receptor β-isoform in the pathogenesis of intrauterine growth restriction. In: Scientific Reports. 2016 ; Vol. 6. pp. 28811.
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Powell, KL, Stevens, V, Upton, DH, McCracken, SA, Simpson, AM, Cheng, Y, Tasevski, V, Morris, JM & Ashton, AW 2016, 'Role for the thromboxane A2 receptor β-isoform in the pathogenesis of intrauterine growth restriction' Scientific Reports, vol. 6, 28811, pp. 28811. https://doi.org/10.1038/srep28811

Role for the thromboxane A2 receptor β-isoform in the pathogenesis of intrauterine growth restriction. / Powell, Katie L; Stevens, Veronica; Upton, Dannielle H; McCracken, Sharon A; Simpson, Ann M; Cheng, Yan; Tasevski, Vitomir; Morris, Jonathan M; Ashton, Anthony W.

In: Scientific Reports, Vol. 6, 28811, 01.07.2016, p. 28811.

Research output: Contribution to journalArticleResearchpeer-review

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