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The importance of cysteine cathepsin proteases for placental development

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Abstract

The typically lysosomal family of cysteine cathepsin proteases has been implicated in the development of the placenta in particular, from studies in the mouse. Here, we analysed overall expression, regulation and presence of transcript isoforms of cysteine cathepsins during human extra-embryonic development. All 11 family members are expressed in human placental tissues, and many are differentially regulated during gestation. Several cysteine cathepsins exhibit deregulated expression levels in placentas from pregnancies complicated by pre-eclampsia. The localization of cathepsin B predominantly in placental and decidual macrophages suggests a role in the physiological functions of these cells in mediating villous angiogenesis and decidual apoptosis. Cathepsin L levels are highest in a subpopulation of invasive cytotrophoblasts. Reflecting the expression pattern of two murine cathepsins, these data give insights into the evolutionary conservation of cathepsin function that is not necessarily exhibited by gene pairs defined by highest sequence similarity. Furthermore, cathepsin L protein localization in uterine epithelial cells demonstrates the in vivo occurrence of intranuclear cathepsin L isoforms. The zonally restricted expression of cathepsin in the syncytiotrophoblast may be important for the metabolic breakdown of maternal nutrients. Overall, the distribution and abnormal expression levels in pre-eclamptic placentas indicate that cysteine cathepsins may play important roles during normal placentation and in the etiology of pre-eclampsia.

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Acknowledgements

The authors would like to thank Drs. M. Sullivan and S. Walker for materials and help with the informatics analysis. This work was supported by an MRC Career Development Award to M.H. and a Wellcome Trust postdoctoral fellowship to S.L.W.

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Authors and Affiliations

  1. Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Cambridge, CB2 4AT, UK

    Aikaterini Varanou, Sarah L. Withington & Myriam Hemberger

  2. St. Mary’s NHS Trust Hospital, Praed Street, London, W2 1NY, UK

    Lorin Lakasing

  3. Institute of Reproductive and Developmental Biology, Imperial College London, Du Cane Road, London, W12 0NN, UK

    Catherine Williamson

  4. Department of Anatomy, University of Cambridge, Downing Street, Cambridge, CB2 3DY, UK

    Graham J. Burton

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  1. Aikaterini Varanou
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  2. Sarah L. Withington
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  3. Lorin Lakasing
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  4. Catherine Williamson
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  5. Graham J. Burton
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  6. Myriam Hemberger
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Correspondence to Myriam Hemberger.

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Varanou, A., Withington, S.L., Lakasing, L. et al. The importance of cysteine cathepsin proteases for placental development. J Mol Med 84, 305–317 (2006). https://doi.org/10.1007/s00109-005-0032-2

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