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Kisspeptins and the placenta: Regulation of trophoblast invasion

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Abstract

The invasion of extravillous trophoblasts into the uterine wall is of crucial importance for placental and fetal development, and its dysregulation has been implicated in a wide spectrum of abnormal pregnancies. Mechanistically, trophoblast invasion strongly resembles the invasion of tumour cells, but differs from it by tight regulation in time and space. This regulation is accomplished by different factors including cytokines and hormones, which are produced by both fetal as well as maternal tissues i.e., placenta and uterus, respectively. Recently, products of the KiSS-1 gene (kisspeptins) have been identified to not only inhibit metastasis in various tumours, but also to repress trophoblast invasion via binding to the G protein-coupled receptor KiSS-1R. In the placenta, expression levels of kisspeptins and their receptor are highest in the first trimester in humans and at day 12.5 in rats, respectively. This coincides with the time when invasiveness peaks and invasion regulation is of central importance. Human kisspeptins are predominantly produced by the syncytiotrophoblast, whereas KiSS-1R is additionally expressed on the invading extravillous trophoblasts indicating a paracrine regulation of extravillous trophoblast invasion by the syncytiotrophoblast. In the structurally different rat placenta both KiSS-1 and its receptor are predominantly expressed by the invasive trophoblast giant cells, thus establishing an autocrine system in the invasion regulation of this trophoblast subpopulation. Amongst all kisspeptins the highly conserved kisspeptin Kp-10 has strongest invasion inhibiting effects suggesting its major role in regulation of trophoblast invasion.

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Acknowledgments

This work was supported by grants 7535, 7793, 10053, 10896 and 11964, Jubilee Fund, Austrian National Bank, Vienna to Gernot Desoye and by grant P17894-B14, Austrian Science Fund, Vienna, to Martin Knöfler.

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Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, Medical University of Graz, Auenbruggerplatz 14, 8036, Graz, Austria

    Ursula Hiden & Gernot Desoye

  2. Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria

    Martin Bilban

  3. Department of Obstetrics and Gynaecology, Medical University of Vienna, Vienna, Austria

    Martin Knöfler

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  1. Ursula Hiden
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  2. Martin Bilban
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Correspondence to Ursula Hiden.

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Hiden, U., Bilban, M., Knöfler, M. et al. Kisspeptins and the placenta: Regulation of trophoblast invasion. Rev Endocr Metab Disord 8, 31–39 (2007). https://doi.org/10.1007/s11154-007-9030-8

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  • DOI: https://doi.org/10.1007/s11154-007-9030-8

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