Evidence from the very beginning: endoglandular trophoblasts penetrate and replace uterine glands in situ and in vitro.
OBJECTIVE
How is histiotrophic nutrition of the embryo secured during the first trimester of pregnancy?


CONCLUSIONS
Rather than specifically focusing on invasion into spiral arteries, extravillous trophoblasts also invade into uterine glands (endoglandular trophoblast) from the very beginning and open them toward the intervillous space.


BACKGROUND
Extravillous trophoblasts can be found in close contact and within the lumen of uterine glands, sometimes replacing glandular epithelial cells.


METHODS
As well as extensive screening of specimens from first trimester placentation sites in situ we used a previously established three-dimensional co-culture in vitro model system of first trimester villous explants with non-invaded decidua parietalis.


METHODS
First trimester placentas were obtained from elective terminations of pregnancies (n = 48) at 5-11 weeks of gestational age. A subset was processed for confrontation co-culture (n = 31). Invaded decidua basalis was obtained from 20 placentas. All tissues were sectioned, subsequently immunostained and immunodoublestained with antibodies against keratin 7 (KRT7), major histocompatibility complex, class I, G (HLA-G), matrix metallopeptidase 9 (MMP9), von Willebrand factor (VWF) and the appropriate Immunoglobulin G (IgG) negative controls. Replacement of endothelial/epithelial cells by extravillous trophoblasts was quantified semi-quantitatively. Additionally, hematoxylin and eosin-stained archival specimens from early implantation sites were assessed.


RESULTS
The earliest available specimen was from around Day 10 after conception; already at this stage trophoblasts had penetrated into uterine glands and had started to replace the epithelium of the glands. Endoglandular trophoblasts replaced uterine glands in vitro and in situ and could be found in the lumen of invaded glands. Quantitative analysis revealed significantly more replacement of epithelial cells in glands (63.8 ± 22.1%) compared with endothelial cells in vessels (26.4 ± 8.8%). Accumulated detached glandular epithelial cells could be repeatedly observed in the lumen of invaded glands. Additionally, in areas of trophoblast invasion the glandular epithelium seemed to be completely disintegrated compared with glandular epithelium in the non-invaded parts of the decidua. Whole tissue specimens were used in vitro and in situ instead of cell lines; these systems mostly maintain the context of the in vivo situation.


CONCLUSIONS
This is a descriptive study supported by in vitro experiments. However, a histological section will always only be a snapshot and quantification from histological sections has its limitations.


CONCLUSIONS
This study further strengthens the hypothesis of histiotrophic nutrition of the embryo prior to the establishment of the maternal blood flow toward the placenta. Invasion of uterine glands by endoglandular trophoblasts may have more impact on the outcome of early pregnancy than assumed up to now.
Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Harrachgasse 21/7, 8010 Graz, Austria g.moser@medunigraz.at.
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G
Moser
Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Harrachgasse 21/7, 8010 Graz, Austria.
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G
Weiss
Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Harrachgasse 21/7, 8010 Graz, Austria.
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M
Gauster
Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Harrachgasse 21/7, 8010 Graz, Austria.
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M
Sundl
Institute of Cell Biology, Histology and Embryology, Medical University of Graz, Harrachgasse 21/7, 8010 Graz, Austria.
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B
Huppertz
D018920:Coculture Techniques; D003656:Decidua / Q000166:cytology*; D005260:Female; D006801:Humans; D010920:Placenta / Q000166:cytology*; D010929:Placentation / Q000502:physiology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D014327:Trophoblasts / Q000166:cytology*
co-culture; endoglandular trophoblast; implantation; invasion; model system; placenta; uterine gland