Role for the thromboxane A 2 receptor β-isoform in the pathogenesis of intrauterine growth restriction

Powell, KL; Stevens, V; Upton, DH; McCracken, SA; Simpson, AM; Cheng, Y; Tasevski, V; Morris, JM; Ashton, AW

Role for the thromboxane A 2 receptor β-isoform in the pathogenesis of intrauterine growth restriction

Powell, KL Stevens, V Upton, DH

McCracken, SA Simpson, AM

Cheng, Y Tasevski, V Morris, JM Ashton, AW

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Publication Type:: Journal Article
Citation:: Scientific Reports, 2016, 6
Issue Date:: 2016-07-01

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Field	Value	Language
dc.contributor.author	Powell, KL	en_US
dc.contributor.author	Stevens, V	en_US
dc.contributor.author	Upton, DH https://orcid.org/0000-0002-4091-4208	en_US
dc.contributor.author	McCracken, SA	en_US
dc.contributor.author	Simpson, AM https://orcid.org/0000-0002-2249-5097	en_US
dc.contributor.author	Cheng, Y	en_US
dc.contributor.author	Tasevski, V	en_US
dc.contributor.author	Morris, JM	en_US
dc.contributor.author	Ashton, AW	en_US
dc.date.available	2016-06-08	en_US
dc.date.issued	2016-07-01	en_US
dc.identifier.citation	Scientific Reports, 2016, 6	en_US
dc.identifier.uri	http://hdl.handle.net/10453/91515
dc.description.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 (TXA 2 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.	en_US
dc.relation.ispartof	Scientific Reports	en_US
dc.relation.isbasedon	10.1038/srep28811	en_US
dc.subject.mesh	Adult	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Animals, Newborn	en_US
dc.subject.mesh	Cell Line, Tumor	en_US
dc.subject.mesh	Female	en_US
dc.subject.mesh	Fetal Growth Retardation	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Hypoxia	en_US
dc.subject.mesh	Male	en_US
dc.subject.mesh	Mice, Inbred C57BL	en_US
dc.subject.mesh	Mice, Transgenic	en_US
dc.subject.mesh	Placenta	en_US
dc.subject.mesh	Pregnancy	en_US
dc.subject.mesh	Protein Isoforms	en_US
dc.subject.mesh	Receptors, Thromboxane A2, Prostaglandin H2	en_US
dc.subject.mesh	Thromboxane A2	en_US
dc.subject.mesh	Trophoblasts	en_US
dc.title	Role for the thromboxane A 2 receptor β-isoform in the pathogenesis of intrauterine growth restriction	en_US
dc.type	Journal Article
utslib.citation.volume	6	en_US
utslib.for	0604 Genetics	en_US
utslib.for	1103 Clinical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
utslib.copyright.status	open_access
pubs.publication-status	Published	en_US
pubs.volume	6	en_US

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 (TXA 2 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.

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http://hdl.handle.net/10453/91515