ACPS Seminar 2014 - Implantation

From Embryology
Understanding Implantation and the new Uterine Tube Biobank
Tuesday 18th March 6.00pm - Level 4 Seminar Space, Lowy Cancer Research Centre, Building C25 Kensington Campus, UNSW
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Dr Mark Hill

School of Medical Sciences E: m.hill@unsw.edu.au

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Human Development - Week 1

  • Key developmental changes during Week 1 (GA week 3)
  • Transport along uterine tube.
Week1 summary.jpg
<mediaplayer width='500' height='450' image="http://embryology.med.unsw.edu.au/embryology/images/0/07/Human_blastocyst_day_1-5.jpg">File:Human_blastocyst_day_3-6.mp4</mediaplayer>
morula to blastocyst [1]

Human Development - Week 2

  • Process of implantation during week 2 (GA week 4) of development in humans.
<mediaplayer width='250' height='260' image="http://php.med.unsw.edu.au/embryology/images/a/a9/Week2_001_icon.jpg">File:Week2_001.mp4</mediaplayer> The beginning of the animation shows adplantation to the the uterus lining (endometrium epithelium).
  • green cells - trophoblast layer of the conceptus
  • blue cells - epiblast layer of the bilaminar embryo
  • yellow cells - hypoblast layer of the bilaminar embryo
  • white cells - uterine endometrium epithelium
  • red - maternal blood vessel
Stage5 bf08.jpg Stage5 bf04.jpg
Section view Surface view

Corpus luteum supported by trophoblast secreted hCG.

Human ovary - corpus luteum 01.jpg

Early Implantation

  • Most data from animal models (mouse) of implantation.
  • Very little human data for early (first trimester) events.
Adplantation Signaling [2]
Implantation cartoon 01.jpg
Early Implantation Signaling[2]
Implantation cartoon 02.jpg

Ectopic Implantation

The movie shows an ectopic embryo (less than GA 10 weeks) implanted in the left uterine tube.
  • RT - Normal Right Tube, the movie starts by showing the normal right uterine tube.
  • LT - Ectopic Left Tube, the scan then moves to the left uterine tube (LT) where ectopic implantation has occurred.
  • L OV - Also visible is the left ovary
  • UT - uterus.
Ectopic GA Week 7 Ectopic GA Week 10
Stage14 bf20.jpg Stage20 bf12.jpg

Image: Dr Steven O'Connor (Houston, Texas)

First trimester placental villi Term placental villi
Placenta anchoring villi.jpg Placental villi 4.jpg
  • Ectopic Model for implantation - some differences (e.g. Endocannabinoids G protein-coupled cannabinoid receptor CB1, ectopic pregnancy show down-regulation[3])

Uterine Implantation

Placenta abnormalities.jpg
  • Placenta Accreta - Abnormal adherence, with absence of decidua basalis. The incidence of placenta accreta also significantly increases in women with previous cesarean section compared to those without a prior surgical delivery.
  • Placenta Increta - Occurs when the placenta attaches deep into the uterine wall and penetrates into the uterine muscle, but does not penetrate the uterine serosa. Placenta increta accounts for approximately 15-17% of all cases.
  • Placenta Percreta - Placental villi penetrate myometrium and through to uterine serosa.

Tube Biobank

Ectopic tubal cartoon.jpg
  • Most published human studies are based upon only a very few tissue samples.
  • Our Biobank tissues will also be available to other implantation researchers.
  • Approval to collect tissue from multiple sites.

HFTB graph 4.jpg

Tube Analysis Techniques

  • Analysing the proteins expressed at the site of implantation (fetal and maternal).
  • Analysing the messenger RNA (mRNA) that encodes protein expression.
  • Analysis of microRNA (miRNA) that regulates gene and protein expression.
  • Later DNA genetic analysis (are there ectopic implantation associated genes?).


Protein Expression

Sandwich ELISA.jpg Cryostat sectioning.jpg

mRNA Expression

Microarray technology.jpg

Immune Protection

  • Expression by fetal cells protects from maternal immune rejection.


HLA-G - Human leukocyte antigen G (HLA-G, HLA-6.0; HLA60, T-CELL A LOCUS; TCA)

  • HLA-G is a non-classical HLA class-Ib molecule expressed by the extravillous cytotrophoblasts (EVT) of the placenta.
  • 338 AA protein, mRNA differential splicing gives rise to 7 isoforms: 4 membrane-bound forms (HLA-G1, G2, G3, G4) and 3 soluble forms (sHLA-G5, G6, G7).
  • miRNA regulated expression.
Placenta anchoring villi.jpg Trophoblast HLA-G expression 01.jpg

HLA-G expression (red) on trophoblast cell columns (CC) and extravillous trophoblasts.[4]

Summary

Early placental structure.jpg
  • We have established a Uterine Tube Biobank at UNSW.
  • First samples collected Sep 2013.
  • We now have patient samples from:
    • ectopic implantation tube
    • control tube, from outside the implantation site
    • control tube, from non-pregnant tube.
  • Hope to also have control tube from hormonally induced pseudo-pregnacy.
  • Three research students (Tatiana, Chi and Liz) working on the project.
    • preparing protein, mRNA, miRNA and DNA.
    • analysing expression of implantation associated proteins in these tissues.
  • First study of a large number of first trimester implantation samples.





Special Thanks

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  • Patients who have donated to this study.
  • Prof William Ledger my clinical collaborator.
  • Dr Anusha Hettiaratchi the Manager of Lowy Biorepository.
  • Dr Tatiana Zandanova, Ngoc Chi Vo and Elizabeth Dalton three research students currently developing the project.
  • Australian Centre for Perinatal Science for supporting developmental research and researchers.








Links: Implantation | Ectopic Implantation | Week 2 | Trophoblast

External Links

External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.

References

  1. <pubmed>20890283</pubmed>| Nat Biotechnol.
  2. 2.0 2.1 <pubmed>23223073</pubmed>| Nat Med
  3. <pubmed>19093002</pubmed>
  4. <pubmed>22438923</pubmed>| PLoS One.




Cite this page: Hill, M.A. (2019, July 23) Embryology ACPS Seminar 2014 - Implantation. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/ACPS_Seminar_2014_-_Implantation

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© Dr Mark Hill 2019, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G