Elsevier

Placenta

Volume 56, August 2017, Pages 19-26
Placenta

Implantation and extravillous trophoblast invasion: From rare archival specimens to modern biobanking

https://doi.org/10.1016/j.placenta.2017.02.007Get rights and content

Highlights

  • Beside spiral arteries extravillous trophoblasts also invade into uterine glands and veins.

  • Endoglandular trophoblast especially invade at the edge of a developing placenta in utero.

  • Implanting blastocyst and uterine glands are already in close contact at day 10 pc.

  • The pre-analytical phase has fundamental impact on study outcome.

Abstract

Extravillous trophoblast invasion serves to attach the placenta to the uterus and to enable access to nutrients for the embryo throughout pregnancy – secretions of the uterine glands in the first trimester, maternal blood in the second and third trimester. For assessing extravillous trophoblast invasion, histology (in combination with immunohistochemistry) still plays a major role in placental research. This is especially true for the re-assessment of rare archival specimens from early human implantation sites or placenta in utero with the background of recent knowledge which may help to strengthen current hypotheses. This review summarizes the recently expanded picture of extravillous trophoblast invasion, gives an overview about fundamental archival specimens in placental research, presents new images of archival specimens, gives insights into the latest developments in the field of biobanking and provides insight into the current situation on sample usage in the absence of biobanks. Modern techniques allow expanding our hitherto believed concept of extravillous trophoblast invasion, which is not restricted to spiral arteries: Extravillous trophoblasts also invade into uterine glands and uterine veins and thereby connect all these luminal structures with the intervillous space. All biomedical research dramatically depends on the quality of the assessed biological samples. Hence, researchers should be aware that the time between collection of a sample from a body and the beginning of analysis (pre-analytical phase) may have more impact on the outcome of a study than previously assumed.

Introduction

Although there is a huge variety of highly sophisticated omics technologies available today, one can still learn a lot from histology and morphological assessment of tissues and organs. In placental research, histology in combination with immunohistochemistry and electron microscopy still plays a major role in identifying new players in the interaction between mother and fetus. Especially, histology of rare archival specimens from early human implantation sites or placenta in utero can be of great value.

At the same time, science has evolved and has led to the development of structured and systematic collections of samples to be used in research, biobanks. Today, biobanks have taken over a major role in biomedical research, offering the hope to enable higher sample quality, better linkage to clinical data and less garbage in – garbage out when analyzing human-derived samples.

Looking at placental development, extravillous trophoblasts originate from the distal side of trophoblast cell columns derived from cytotrophoblasts of anchoring villi. Within these cell columns proliferative but non-invasive cytotrophoblasts switch to an invasive but non-proliferative extravillous phenotype and start to enter maternal tissues (interstitial trophoblast) [1]. From a histological point of view one of the most important characteristics of extravillous trophoblasts is their expression of major histocompatibility complex, class I, G (HLA-G) [2], [3], [4]. Only HLA-G is a specific marker for extravillous trophoblasts, rather than the still commonly used cytokeratin 7. The latter also reacts with maternal glandular epithelial cells [5]; this may lead to the misidentification of maternal uterine glands and maternal vessels where in the latter the endothelium is replaced by extravillous trophoblasts. Researchers should take care when choosing antibodies against HLA-G, since not all antibodies recognize HLA-G1, which is the only isoform expressed at the cell surface [6]. The anti-HLA-G antibody we recommend to use is the clone 4H84; it recognizes all isoforms of HLA-G, including HLA-G1 (which is the full length, membrane bound isoform, expressed on the cell surface) [5].

This review is divided in three parts, the first part summarizes the latest developments in the field of extravillous trophoblast invasion towards uterine glands and vessels. The second part gives an overview about fundamental archival specimens in placental research for “placental rookies”. For well-established placental researchers some new images of archival specimens are discussed in the context of the latest literature. In the third part, this review aims at extending this view to the latest development in the field of biobanking and provides insight into the current situation on sample usage in the absence of biobanks.

Section snippets

Extended view on extravillous trophoblast invasion into uterine vessels and glands

It is commonly accepted, that extravillous trophoblasts start their invasive pathway by invading the decidual stroma (interstitial trophoblast) [7] and thereby anchor the placenta to the uterus. It is also long accepted that extravillous trophoblasts invade and transform uterine spiral arteries (endovascular trophoblast) [8], [9]. This leads to plugging of such vessels during the first trimester of pregnancy and after release of the plugs enables flow of maternal blood towards the placenta

Publicly available archival human implantation sites

As can be seen from the achievements above, revisiting archival material with current knowledge may well enable detection of new, so far undetected features. Unfortunately, today only a few images from a handful of human early implantation sites are available for the scientific (and public) community. As an example we describe the image collections of the well-known collections that are publicly available at the Centre for Trophoblast Research (http://www.trophoblast.cam.ac.uk/Resources). These

Aspects of modern biobanking

As can be seen from the list above, the number of options and chances for a suboptimal treatment of samples is extremely high. Typical post-sampling variables during the pre-analytical phase include but are not limited to the time between collection and fixation, the temperature during transport, the storage temperature and duration, the number of freeze-thaw cycles and the extraction method for biomolecules. This list needs to be extended to the variables at the time of analysis, since taking

Conclusion

Archival material of human implantation sites and placentas in situ from hysterectomy specimens are still an invaluable treasure for placental research, especially when re-assessing it with the background of the recent state of knowledge. The hypothesis that there is a direct connection between the implanting blastocyst and uterine glands was stated more than hundred years ago and only now there is proof and evidence for this. Modern techniques allow expanding our hitherto believed concept of

Funding

This work was supported by the Austrian Science Fund (grant P24739-B23, granted to G.M.). G.M. was funded by the Austrian Science Fund (grant P24739-B23). No competing financial interests exist.

Conflict of interest

There is no conflict of interest of any of the authors.

Acknowledgements

Thanks to Monika Siwetz, Monika Sundl and Rudolf Schmied for their valuable help and expertise.

References (36)

  • K. Benirschke et al.

    Nonvillous parts and trophoblast invasion

  • M.T. McMaster et al.

    Human placental HLA-G expression is restricted to differentiated cytotrophoblasts

    J. Immunol. Balt. Md

    (1995)
  • A.P. Weetman

    The immunology of pregnancy

    Thyroid. Off. J. Am. Thyroid. Assoc.

    (1999)
  • K. Benirschke et al.

    Early developement of the human placenta

  • G. Weiss et al.

    The trophoblast plug during early pregnancy: a deeper insight

    Histochem. Cell Biol.

    (2016)
  • G. Moser et al.

    Endoglandular trophoblast, an alternative route of trophoblast invasion? Analysis with novel confrontation co-culture models

    Hum. Reprod.

    (2010)
  • G. Moser et al.

    Evidence from the very beginning: endoglandular trophoblasts penetrate and replace uterine glands in situ and in vitro

    Hum. Reprod. Oxf. Engl.

    (2015)
  • G.J. Burton et al.

    Uterine glands provide histiotrophic nutrition for the human fetus during the first trimester of pregnancy

    J. Clin. Endocrinol. Metab.

    (2002)
  • Cited by (51)

    • Maternal metabolism influences neural tube closure

      2023, Trends in Endocrinology and Metabolism
    • Elevated expression of galectin-3, thioredoxin and thioredoxin interacting protein in preeclampsia

      2021, Pregnancy Hypertension
      Citation Excerpt :

      We showed that Gal-3 protein expression was increased in placental tissue among women with PE, particularly in EVT cells. EVT have a major role in the pathogenesis of PE, which appears to be related to inadequate invasion of uterine spiral arteries into the placenta [36]. This observation may indicate that PE is related to changes in the placenta that occur on an intracellular level and that the placenta might protect the fetus from the inflammatory effects of Gal-3.

    • Exploring the role of LC-PUFA metabolism in pregnancy complications

      2020, Prostaglandins Leukotrienes and Essential Fatty Acids
      Citation Excerpt :

      During implantation, LC-PUFA in particular are required for structural and functional growth of the developing embryo at implantation site. Implantation and placentation depends on the invasive properties of the trophoblast [66]. Invasive trophoblasts play a crucial role in successful pregnancy outcome.

    • The unique applicability of the human placenta to the Adverse Outcome Pathway (AOP) concept: the placenta provides fundamental insights into human organ functions at multiple levels of biological organization

      2020, Reproductive Toxicology
      Citation Excerpt :

      When these cells have undergone a final differentiation step into multinuclear trophoblast giant cells, they lose their invasive abilities. The interstitial trophoblasts additionally give rise to different endovascular trophoblast populations, namely endoglandular, endovenous, endoarterial, and endolymphatic trophoblasts that invade uterine glands, veins, arteries and lymph vessels, respectively, thus connecting these structures to the intervillous space [22]. The vessel walls of maternal spiral arteries are not only invaded, but transformed by the endovascular invasion.

    • Maternal dietary fatty acids and their roles in human placental development

      2020, Prostaglandins Leukotrienes and Essential Fatty Acids
    View all citing articles on Scopus
    View full text