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Human endometrial c...
Human endometrial cell-type-specific RNA sequencing provides new insights into the embryo-endometrium interplay
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- Koel, Mariann (författare)
- Competence Ctr Hlth Technol, Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, Dept Cell Biol, Tartu, Estonia.
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- Krjutskov, Kaarel (författare)
- Karolinska Institutet
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- Saare, Merli (författare)
- Competence Ctr Hlth Technol, Tartu, Estonia.;Univ Tartu, Inst Clin Med, Dept Obstet & Gynaecol, Tartu, Estonia.
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- Samuel, Kulli (författare)
- Competence Ctr Hlth Technol, Tartu, Estonia.
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- Lubenets, Dmitri (författare)
- Univ Tartu, Inst Mol & Cell Biol, Dept Cell Biol, Tartu, Estonia.
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- Katayama, Shintaro (författare)
- Karolinska Institutet
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- Einarsdottir, Elisabet (författare)
- KTH,Genteknologi,Univ Helsinki, Res Programs Unit, Stem Cells & Metab Res Program, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland.
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- Vargas, Eva (författare)
- Univ Granada, Fac Sci, Dept Biochem & Mol Biol, Fuente Nueva S-N, Granada 18071, Spain.;Inst Invest Biosanitaria ibsGRANADA, Granada, Spain.;Univ Jaen, Fac Expt Sci, Dept Expt Biol, Syst Biol Unit, Jaen, Spain.
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- Sola-Leyva, Alberto (författare)
- Univ Granada, Fac Sci, Dept Biochem & Mol Biol, Fuente Nueva S-N, Granada 18071, Spain.;Inst Invest Biosanitaria ibsGRANADA, Granada, Spain.
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- Lalitkumar, Parameswaran Grace (författare)
- Karolinska Institutet
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- Gemzell-Danielsson, Kristina (författare)
- Karolinska Inst, Dept Womens & Childrens Hlth, Div Obstet & Gynecol, Stockholm, Sweden.;Karolinska Univ Hosp, Stockholm, Sweden.
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- Blesa, David (författare)
- IGENOMIX, Dept Prod Dev, Valencia, Spain.
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- Simon, Carlos (författare)
- Univ Valencia, Dept Obstet & Gynecol, Valencia, Spain.;INCLIVA Valencia, Valencia, Spain.;Harvard Univ, Dept Obstet & Gynecol, BIDMC, Boston, MA USA.
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- Lanner, Fredrik (författare)
- Karolinska Institutet
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- Kere, Juha (författare)
- Karolinska Institutet
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- Salumets, Andres (författare)
- Karolinska Institutet
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- Altmae, Signe (författare)
- Karolinska Institutet
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Karolinska Institutet Competence Ctr Hlth Technol, Tartu, Estonia;Univ Tartu, Inst Mol & Cell Biol, Dept Cell Biol, Tartu, Estonia. (creator_code:org_t)
- 2022-10-13
- 2022
- Engelska.
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Ingår i: HUMAN REPRODUCTION OPEN. - : Oxford University Press (OUP). - 2399-3529. ; 2022:4
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- STUDY QUESTION: Which genes regulate receptivity in the epithelial and stromal cellular compartments of the human endometrium, and which molecules are interacting in the implantation process between the blastocyst and the endometrial cells? SUMMARY ANSWER: A set of receptivity-specific genes in the endometrial epithelial and stromal cells was identified, and the role of galectins (LGALS1 and LGALS3), integrin beta 1 (ITGB1), basigin (BSG) and osteopontin (SPP1) in embryo-endometrium dialogue among many other protein-protein interactions were highlighted. WHAT IS KNOWN ALREADY: The molecular dialogue taking place between the human embryo and the endometrium is poorly understood due to ethical and technical reasons, leaving human embryo implantation mostly uncharted. STUDY DESIGN, SIZE, DURATION: Paired pre-receptive and receptive phase endometrial tissue samples from 16 healthy women were used for RNA sequencing. Trophectoderm RNA sequences were from blastocysts. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cell-type-specific RNA-seq analysis of freshly isolated endometrial epithelial and stromal cells using fluorescence-activated cell sorting (FACS) from 16 paired pre-receptive and receptive tissue samples was performed. Endometrial transcriptome data were further combined in silico with trophectodermal gene expression data from 466 single cells originating from 17 blastocysts to characterize the first steps of embryo implantation. We constructed a protein-protein interaction network between endometrial epithelial and embryonal trophectodermal cells, and between endometrial stromal and trophectodermal cells, thereby focusing on the very first phases of embryo implantation, and highlighting the molecules likely to be involved in the embryo apposition, attachment and invasion. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 499 epithelial and 581 stromal genes were up-regulated in the receptive phase endometria when compared to pre-receptive samples. The constructed protein-protein interactions identified a complex network of 558 prioritized protein-protein interactions between trophectodermal, epithelial and stromal cells, which were grouped into clusters based on the function of the involved molecules. The role of galectins (LGALS1 and LGALS3), integrin beta 1 (ITGB1), basigin (BSG) and osteopontin (SPP1) in the embryo implantation process were highlighted. LARGE SCALE DATA: RNA-seq data are available at www.ncbi.nlm.nih.gov/geo under accession number GSE97929. LIMITATIONS, REASONS FOR CAUTION: Providing a static snap-shot of a dynamic process and the nature of prediction analysis is limited to the known interactions available in databases. Furthermore, the cell sorting technique used separated enriched epithelial cells and stromal cells but did not separate luminal from glandular epithelium. Also, the use of biopsies taken from non-pregnant women and using spare IVF embryos (due to ethical considerations) might miss some of the critical interactions characteristic of natural conception only. WIDER IMPLICATIONS OF THE FINDINGS: The findings of our study provide new insights into the molecular embryo-endometrium interplay in the first steps of implantation process in humans. Knowledge about the endometrial cell-type-specific molecules that co-ordinate successful implantation is vital for understanding human reproduction and the underlying causes of implantation failure and infertility. Our study results provide a useful resource for future reproductive research, allowing the exploration of unknown mechanisms of implantation. We envision that those studies will help to improve the understanding of the complex embryo implantation process, and hopefully generate new prognostic and diagnostic biomarkers and therapeutic approaches to target both infertility and fertility, in the form of new contraceptives.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reproduktionsmedicin och gynekologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Obstetrics, Gynaecology and Reproductive Medicine (hsv//eng)
Nyckelord
- blastocyst
- endometrial epithelium
- embryo implantation
- endometrial receptivity
- endometrial stroma
- interactome
Publikations- och innehållstyp
- ref (ämneskategori)
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Koel, Mariann
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Krjutskov, Kaare ...
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Saare, Merli
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Samuel, Kulli
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Lubenets, Dmitri
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Katayama, Shinta ...
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Einarsdottir, El ...
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Vargas, Eva
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Sola-Leyva, Albe ...
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Lalitkumar, Para ...
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Gemzell-Danielss ...
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Blesa, David
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Simon, Carlos
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Lanner, Fredrik
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Kere, Juha
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Salumets, Andres
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Altmae, Signe
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