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Article << Previous     |     Next >>   Contents Vol 26(2)

PAPPA2 is increased in severe early onset pre-eclampsia and upregulated with hypoxia

Kate Macintire A, Laura Tuohey A, Louie Ye A, Kirsten Palmer A, Michael Gantier B, Stephen Tong A and Tu’uhevaha J. Kaitu’u-Lino A C

A Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, 163 Studley Road, Heidelberg, Vic. 3084, Australia.
B Monash Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton, Vic. 3168, Australia.
C Corresponding author. Email: t.klino@unimelb.edu.au

Reproduction, Fertility and Development 26(2) 351-357 http://dx.doi.org/10.1071/RD12384
Submitted: 29 November 2012  Accepted: 26 January 2013   Published: 14 March 2013


 
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Abstract

Severe early onset pre-eclampsia is a serious pregnancy complication, believed to arise as a result of persistent placental hypoxia due to impaired placentation. Pregnancy-associated plasma protein A2 (PAPPA2) is very highly expressed in the placenta relative to all other tissues. There is some evidence that PAPPA2 mRNA and protein are increased in association with pre-eclampsia. The aim of the present study was to characterise the mRNA and protein expression, as well as localisation, of PAPPA2 in an independent cohort of severe early onset pre-eclamptic placentas. We also examined whether exposing placental explants to hypoxia (1% oxygen) changed the expression of PAPPA2. Expression of PAPPA2 mRNA and protein was upregulated in severe early onset pre-eclamptic placentas compared with preterm controls and localised to the syncytiotrophoblast. Interestingly, protein localisation was markedly reduced in term placenta. Syncytialisation of BeWo cells did not change PAPPA2 expression. However, hypoxia upregulated PAPPA2 mRNA and protein expression in primary placental explants. Together, our data suggest that PAPPA2 may be upregulated in severe pre-eclampsia and, functionally, this may be mediated via increased placental hypoxia known to occur with this pregnancy disorder.

Additional keywords: placenta, pregnancy.


References

American Congress of Obstetricians and Gynecologists (ACOG) (2002). Diagnosis and management of pre-eclampsia and eclampsia. ACOG Practice Bulletin No. 33. Obstet. Gynecol. 99, 159–167.
CrossRef | PubMed |

Aye, I. L., Waddell, B. J., Mark, P. J., and Keelan, J. A. (2011). Oxysterols inhibit differentiation and fusion of term primary trophoblasts by activating liver X receptors. Placenta 32, 183–191.
CrossRef | CAS | PubMed |

Buimer, M., Keijser, R., Jebbink, J. M., Wehkamp, D., van Kampen, A. H., Boer, K., van der Post, J. A., and Ris-Stalpers, C. (2008). Seven placental transcripts characterize HELLP-syndrome. Placenta 29, 444–453.
CrossRef | CAS | PubMed |

Conover, C. A., Boldt, H. B., Bale, L. K., Clifton, K. B., Grell, J. A., Mader, J. R., Mason, E. J., and Powell, D. R. (2011). Pregnancy-associated plasma protein-A2 (PAPP-A2): tissue expression and biological consequences of gene knockout in mice. Endocrinology 152, 2837–2844.
CrossRef | CAS | PubMed |

Culver, C., Sundqvist, A., Mudie, S., Melvin, A., Xirodimas, D., and Rocha, S. (2010). Mechanism of hypoxia-induced NF-kappaB. Mol. Cell. Biol. 30, 4901–4921.
CrossRef | CAS | PubMed |

Grill, S., Rusterholz, C., Zanetti-Dallenbach, R., Tercanli, S., Holzgreve, W., Hahn, S., and Lapaire, O. (2009). Potential markers of preeclampsia: a review. Reprod. Biol. Endocrinol. 7, 70.
CrossRef | PubMed |

Levine, R. J., Maynard, S. E., Qian, C., Lim, K.-H., England, L. J., Yu, K. F., Schisterman, E. F., Thadhani, R., Sachs, B. P., Epstein, F. H., Sibai, B. M., Sukhatme, V. P., and Karumanchi, S. A. (2004). Circulating angiogenic factors and the risk of preeclampsia. N. Engl. J. Med. 350, 672–683.
CrossRef | CAS | PubMed |

Messeguer, X., Escudero, R., Farre, D., Nunez, O., Martinez, J., and Alba, M. M. (2002). PROMO: detection of known transcription regulatory elements using species-tailored searches. Bioinformatics 18, 333–334.
CrossRef | CAS | PubMed |

Moffett-King, A. (2002). Natural killer cells and pregnancy. Nat. Rev. Immunol. 2, 656–663.
CrossRef | CAS | PubMed |

Nishizawa, H., Pryor-Koishi, K., Suzuki, M., Kato, T., Kogo, H., Sekiya, T., Kurahashi, H., and Udagawa, Y. (2008). Increased levels of pregnancy-associated plasma protein-A2 in the serum of pre-eclamptic patients. Mol. Hum. Reprod. 14, 595–602.
CrossRef | CAS | PubMed |

Paiva, P., Whitehead, C., Saglam, B., Palmer, K., and Tong, S. (2011). Measurement of mRNA transcripts of very high placental expression in maternal blood as biomarkers of preeclampsia. J. Clin. Endocrinol. Metab. 96, E1807–E1815.
CrossRef | CAS | PubMed |

Powe, C. E., Levine, R. J., and Karumanchi, S. A. (2011). Preeclampsia, a disease of the maternal endothelium: the role of antiangiogenic factors and implications for later cardiovascular disease. Circulation 123, 2856–2869.
CrossRef | PubMed |

Redman, C. W., and Sargent, I. L. (2005). Latest advances in understanding preeclampsia. Science 308, 1592–1594.
CrossRef | CAS | PubMed |

Rius, J., Guma, M., Schachtrup, C., Akassoglou, K., Zinkernagel, A. S., Nizet, V., Johnson, R. S., Haddad, G. G., and Karin, M. (2008). NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. Nature 453, 807–811.
CrossRef | CAS | PubMed |

Sibai, B., Dekker, G., and Kupferminc, M. (2005). Pre-eclampsia. Lancet 365, 785–799.
| PubMed |

Sitras, V., Paulssen, R. H., Gronaas, H., Leirvik, J., Hanssen, T. A., Vartun, A., and Acharya, G. (2009). Differential placental gene expression in severe preeclampsia. Placenta 30, 424–433.
CrossRef | CAS | PubMed |

Valbuena-Diez, A. C., Blanco, F. J., Oujo, B., Langa, C., Gonzalez-Nunez, M., Llano, E., Pendas, A. M., Diaz, M., Castrillo, A., Lopez-Novoa, J. M., and Bernabeu, C. (2012). Oxysterol-induced soluble endoglin release and its involvement in hypertension. Circulation 126, 2612–2624.
CrossRef | CAS | PubMed |

Várkonyi, T., Nagy, B., Fule, T., Tarca, A. L., Karaszi, K., Schonleber, J., Hupuczi, P., Mihalik, N., Kovalszky, I., Rigo, J., Meiri, H., Papp, Z., Romero, R., and Than, N. G. (2011). Microarray profiling reveals that placental transcriptomes of early-onset HELLP syndrome and preeclampsia are similar. Placenta 32, S21–S29.
CrossRef | PubMed |

Venkatesha, S., Toporsian, M., Lam, C., Hanai, J., Mammoto, T., Kim, Y. M., Bdolah, Y., Lim, K. H., Yuan, H. T., Libermann, T. A., Stillman, I. E., Roberts, D., D’Amore, P. A., Epstein, F. H., Sellke, F. W., Romero, R., Sukhatme, V. P., Letarte, M., and Karumanchi, S. A. (2006). Soluble endoglin contributes to the pathogenesis of preeclampsia. Nat. Med. 12, 642–649.
CrossRef | CAS | PubMed |

Wagner, P. K., and Christians, J. K. (2010). Altered placental expression of PAPPA2 does not affect birth weight in mice. Reprod. Biol. Endocrinol. 8, 90.
CrossRef | PubMed |

Wagner, P. K., Otomo, A., and Christians, J. K. (2011). Regulation of pregnancy-associated plasma protein A2 (PAPPA2) in a human placental trophoblast cell line (BeWo). Reprod. Biol. Endocrinol. 9, 48.
CrossRef | CAS | PubMed |

Wang, J., Qiu, Q., Haider, M., Bell, M., Gruslin, A., and Christians, J. K. (2009). Expression of pregnancy-associated plasma protein A2 during pregnancy in human and mouse. J. Endocrinol. 202, 337–345.
CrossRef | CAS | PubMed |

Winn, V. D., Gormley, M., Paquet, A. C., Kjaer-Sorensen, K., Kramer, A., Rumer, K. K., Haimov-Kochman, R., Yeh, R. F., Overgaard, M. T., Varki, A., Oxvig, C., and Fisher, S. J. (2009). Severe preeclampsia-related changes in gene expression at the maternal-fetal interface include sialic acid-binding immunoglobulin-like lectin-6 and pappalysin-2. Endocrinology 150, 452–462.
CrossRef | CAS | PubMed |

Zhong, H., and Simons, J. W. (1999). Direct comparison of GAPDH, beta-actin, cyclophilin, and 28S rRNA as internal standards for quantifying RNA levels under hypoxia. Biochem. Biophys. Res. Commun. 259, 523–526.
CrossRef | CAS | PubMed |


   
 
    
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