Variability in mRNA expression of fms-like tyrosine kinase-1 variants in normal and preeclamptic placenta

BMC Research Notes

Annemarie Hennessy²  Joanne M Lind¹  Craig A Lind¹  Christine L Chiu¹  Angela Makris³  Gabriele Bobek¹  Laura Surmon¹ 

[1] School of Medicine, University of Western Sydney, Building 30, Campbelltown Campus, Locked Bag 1797, Penrith, NSW 2751, Australia;The Heart Research Institute, University of Sydney, Sydney, NSW, Australia;Liverpool Hospital, Liverpool, NSW, Australia

关键词: Sampling;    Variability;    sFLT-1;    Preeclampsia;    Placenta;   

Others  :  1134232
DOI  :  10.1186/1756-0500-7-154

 received in 2014-01-02, accepted in 2014-03-13,  发布年份 2014

【 摘 要 】

Background

Preeclampsia is a complication of pregnancy characterised by gestational hypertension and proteinuria and is a leading cause of morbidity and mortality in both mothers and infants. Certain anti-angiogenic factors have long been implicated in the pathogenesis of preeclampsia and the placental expression of factors such as soluble fms-like tyrosine kinase-1 (sFLT-1) are often reported in studies of normal and diseased placentae. Despite evidence showing significant differences in placental gene expression by collection site, many studies fail to provide sufficient details on sample selection and collection.

Findings

With ourselves and others investigating and reporting on the expression of FLT-1 variants and other genes in the placenta of normotensive and preeclamptic patients, we felt it prudent to examine the variation in expression of FLT-1 variants across human placenta. We examined the differential expression of FLT-1 variants in samples obtained from 12 sites on normal and preeclamptic placentae and found expression to be highly variable between sites. We therefore developed an algorithim to calculate the mean expression for any number of these sites collected and in any combination. The coefficient of variation for all combinations of sites was then used to determine the minimum number of sites required to reduce coefficient of variation to below an acceptable 10%. We found that 10 and 11 sites had to be sampled in the normal and preeclamptic placentae respectively to ensure a representative expression pattern for all FLT-1 variants for an individual placenta.

Conclusions

These findings demonstrate significant variation in expression levels of several commonly investigated genes across sites in both normal and preeclamptic placenta. This highlights both the importance of adequate sampling of human placenta for expression studies and the effective communication of sample selection and collection methods, for data interpretation and to ensure the reproducibility and reliability of results and conclusions drawn.

【 授权许可】

   
2014 Surmon et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Woolcock J, Hennessy A, Xu B, Thornton C, Tooher J, Makris A, Ogle R: Soluble Flt-1 as a diagnostic marker of preeclampsia. Aust N Z J Obstet Gynaecol. 2008, 48(1):64-70.
• [2]Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, Schisterman EF, Thadhani R, Sachs BP, Epstein FH, Sibai BM, Sukhatme VP, Karumanchi SA: Circulating angiogenic factors and the risk of preeclampsia. New Engl J Med. 2004, 350(7):672-83.
• [3]Sela S, Itin A, Natanson-Yaron S, Greenfield C, Goldman-Wohl D, Yagel S, Keshet E: A novel human-specific soluble vascular endothelial growth factor receptor 1: cell-type-specific splicing and implications to vascular endothelial growth factor homeostasis and preeclampsia. Circ Res. 2008, 102(12):1566-74.
• [4]Whitehead C, Palmer K, Nilsson U, Gao Y, Saglam B, Lappas M, Tong S: Placental expression of a novel primate-specific splice variant of sFlt-1 is upregulated in pregnancies complicated by severe early onset pre-eclampsia. BJOG 2011, 118(10):1268-71.
• [5]Thomas CP, Andrews JI, Raikwar NS, Kelley EA, Herse F, Dechend R, Golos TG, Liu KZ: A recently evolved novel trophoblast-enriched secreted form of fms-like tyrosine kinase-1 variant is up-regulated in hypoxia and preeclampsia. J Clin Endocrinol Metab. 2009, 94(7):2524-30.
• [6]Makris A, Thornton C, Thompson J, Thomson S, Martin R, Ogle R, Waugh R, McKenzie P, Kirwan P, Hennessy A: Uteroplacental ischemia results in proteinuric hypertension and elevated sFLT-1. Kidney Int 2007, 71(10):977-84.
• [7]Zhou Q, Qiao FY, Zhao C, Liu HY: Hypoxic trophoblast-derived sFlt-1 may contribute to endothelial dysfunction: implication for the mechanism of trophoblast-endothelial dysfunction in preeclampsia. Cell Biol Int 2011, 35(1):61-66.
• [8]Redman CW, Sargent IL: Latest advances in understanding preeclampsia. Science 2005, 308(5728):1592-1594.
• [9]Maynard SE, Karumanchi SA: Angiogenic factors and preeclampsia. Semin Nephrol 2011, 31(1):33-46.
• [10]Mayhew TM: Taking tissue samples from the placenta: an illustration of principles and strategies. Placenta 2008, 29(1):1-14. [Research Support, Non-U.S. Gov’t Review]
• [11]Maynard SE, Min JY, Merchan J, Lim KH, Li J, Mondal S, Libermann TA, Morgan JP, Sellke FW, Stillman IE, Epstein FH, Sukhatme VP, Karumanchi SA: Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia. J Clin Invest. 2003, 111(5):649-58.
• [12]Maynard SE, Venkatesha S, Thadhani R, Karumanchi SA: Soluble Fms-like tyrosine kinase 1 and endothelial dysfunction in the pathogenesis of preeclampsia. Pediatr Res 2005, 57(5 Pt 2):1R-7R.
• [13]Levine RJ, Maynard SE, Qian C, Lim KH, England LJ, Yu KF, Schisterman EF, Thadhani R, Sachs BP, Epstein FH, Sibai BM, Sukhatme VP, Karumanchi SA: Circulating angiogenic factors and the risk of preeclampsia. N Engl J Med 2004, 350(7):672-83.