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New insights to differences in preimplantation embryonic cells bring to light the importance of microscopic analysis in assisted reproduction procedures

Singapore—Researchers at A*STAR’s Institute of Molecular and Cell Biology (IMCB) have developed advanced microscopy technologies to monitor embryo development in real time, revealing how mammalian cells differentiate during the earliest stages of embryonic life. These findings, coupled with the novel imaging technique, hold great potential in shaping how assisted reproduction procedures such as In-Vitro Fertilisation (IVF)[1] and Preimplantation Genetic Diagnosis (PGD)[2] are performed, and making these procedures more effective.

Across the globe, more women are relying on assisted reproduction procedures. Singapore alone, for example, has carried out over 6000 assisted reproduction cycles in 2015, an increase of more than 1000 cycles from 2012[3].

Current IVF procedures assess whether an embryo is suitable for implantation into the mother largely through observable measurements such as gauging if the rate of growth of the embryo is normal. PGD of embryos, on the other hand, is carried out by analysing a randomly extracted embryonic cell for genetic defects, with the assumption that all cells within a preimplantation embryo are identical and that the removal of a single embryonic cell would not affect the overall development of the embryo after implantation.

Contrary to the current conception that every cell within a preimplantation embryo is identical, the team of researchers at IMCB has demonstrated that the cells are in fact differentiated and may play very different roles in later development. By designing new cutting-edge real-time imaging techniques, the researchers were able to examine every cell within a preimplantation mouse embryo without perturbing its development. They observed differences in the way which certain proteins in each cell bind to their target genes. The scientists also observed that there were variances in cell behaviour at every stage of the embryo’s development. As mouse embryos bear strong resemblance to human embryos at early stage development, the findings indicate that cells within a preimplantation human embryo are also not identical.

The study, therefore, refines our understanding of early stage embryonic development and highlights how assisted reproduction procedures such as IVF and PGD may be further enhanced to ensure successful fertilisation, smooth pregnancy and childbirth. Further development of the real-time imaging technique may eventually enable fertility specialists to study the microscopic properties of embryos and decide more precisely if an embryo is suitable for implantation, or screen an embryo for genetic abnormalities using imaging lasers instead of physical manipulation. This would enable better quality control of embryos implanted in mothers hence potentially increasing the chances of success for these procedures through more efficient control of embryo quality.

Dr Nicolas Plachta, Senior Principal Investigator of IMCB, said, “Most laboratories conduct studies on embryonic cells via invasive methods which do not keep the embryo alive. Our lab is the only one in the world imaging single cells in live mammalian embryos at the quantitative level, which allows us to observe every cell within an embryo at every stage of its development. Our findings as a result of this advanced technique have put forth a new paradigm of knowledge that would encourage more detailed microscopic analysis for future assisted reproduction procedures.”

Dr Sadhana Nadarajah, Director of KKIVF Centre and Senior Consultant, Department of Reproductive Medicine, KK Women’s and Children’s Hospital, said, “This novel method of screening embryos is indeed exciting. If it can be successfully used on human embryos, without affecting its successive growth, it will improve the technique of embryo selection in IVF.”

Prof Hong Wanjin, Executive Director of IMCB, said, "In many developed countries like Singapore, women are having children later in their lives, which has been linked to declined fertility. As such, assisted reproduction procedures needs to be constantly improved and made more reliable to help women successfully conceive and sustain a healthy birth rate. Nicolas and his dedicated team of researchers have therefore made a significant breakthrough that could benefit the society greatly."

The study was published in the top-tier scientific journal, Cell, and was also featured as the cover of the journal.

Microscopic image of a four-cell mouse embryo (Image from Dr Nicolas Plachta)

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Notes for Editor:

The research findings described in this media release can be found in the Cell Journal, under the title, “Long-Lived Binding of Sox2 to DNA Predicts Cell Fate in the Four-Cell Mouse Embryo” by Melanie D. White1,3, Juan Francisco Angiolini2,3, Yanina D. Alvarez2,3, Gurpreet Kaur1,3, Ziqing W. Zhao1, Esteban Mocskos2, Luciana Bruno2, Stephanie Bissiere1, Valeria Levi2,*, Nicolas Plachta1,*



1Institute of Molecular and Cell Biology, A*STAR, 61 Biopolis Drive, Singapore 138673, Singapore

2Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, CONICET, Buenos Aires, C1428EHA, Argentina

3Equal contributions

*Authors for correspondence: V.L. (vlevi12@gmail.com); N.P. (plachtan@imcb.a-star.edu.sg)

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For media queries and clarifications, please contact:

Tan Yun Yun
Senior Officer, Corporate Communications
Agency for Science, Technology and Research
Tel: +65 6826 6273 Email: tan_yun_yun@a-star.edu.sg

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About the Agency for Science, Technology and Research (A*STAR)

The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector agency that spearheads economic oriented research to advance scientific discovery and develop innovative technology. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit society.

As a Science and Technology Organisation, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by contributing to societal benefits such as improving outcomes in healthcare, urban living, and sustainability.

We play a key role in nurturing and developing a diversity of talent and leaders in our Agency and Research Institutes, the wider research community and industry. A*STAR oversees 18 biomedical sciences and physical sciences and engineering research entities primarily located in Biopolis and Fusionopolis.

For more information on A*STAR, please visit www.a-star.edu.sg.



About the Institute of Molecular and Cell Biology (IMCB)

The Institute of Molecular and Cell Biology (IMCB) was launched on 23 January 1985, with its official opening ceremony held on 2 October 1987 at the National University of Singapore (NUS). It subsequently became an autonomous research institute (RI) of A*STAR, moving to Biopolis in 2004. IMCB’s vision is to be a premier cell and molecular biology institute which addresses the mechanistic basis of human diseases and its mission is to conduct cutting-edge discovery research in disease pathways; to groom early career researchers to be future leaders in research; and to collaborate with medical and industry communities for research impact. IMCB plays an important role training and recruiting scientific talents, and has contributed to the development of other research entities in Singapore. Its success in fostering a biomedical research culture in Singapore has catalysed Singapore’s transformation into an international hub for biomedical research, development and innovation.

Funded primarily by the Biomedical Research Council (BMRC) of A*STAR, IMCB’s current discovery research includes cell biology in health and disease; animal models of development & disease; cancer & stem cell genetics & genomics; and structural biology & drug discovery. IMCB’s translational research includes humanised model organisms for human diseases; systems approach for disease target identification & validation; and protein engineering & antibody development for diagnostics & therapeutics. Research activities in IMCB are supported by cutting edge infrastructure and facilities including quantitative proteomics; humanised mice; mouse models of human cancer; protein crystallography X-ray; zebrafish for drug metabolism & toxicology; advanced molecular histopathology; imaging & electron microscopy; and DNA sequencing.

For more information about IMCB, visit www.imcb.a-star.edu.sg




[1] In-Vitro Fertilisation (IVF) is a procedure in which eggs (ova) from a woman's ovary are removed and fertilised with sperm in a laboratory procedure, and then the fertilised egg (embryo) is returned to the woman's uterus.

[2] Preimplantation Genetic Diagnosis (PGD) is a screening test used to determine if genetic or chromosomal disorders are present in embryos produced through IVF.

[3]The Straits Times: http://www.straitstimes.com/singapore/health/more-singapore-couples-getting-help-to-conceive


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