Featured Research

from universities, journals, and other organizations

Key component in mother's egg critical for survivial of newly formed embryo

Date:
March 29, 2012
Source:
Agency for Science, Technology and Research (A*STAR), Singapore
Summary:
Scientists have discovered that a protein, called TRIM28, normally present in the mother's egg, is essential right after fertilization, to preserve certain chemical modifications or 'epigenetic marks' on a specific set of genes. This newly published study paves the way for more research to explore the role that epigenetics might play in infertility.

An international team led by scientists at A*STAR's Institute of Medical Biology (IMB) discovered that a protein, called TRIM28, normally present in the mother's egg, is essential right after fertilisation[1], to preserve certain chemical modifications or 'epigenetic marks' on a specific set of genes. This newly published study paves the way for more research to explore the role that epigenetics might play in infertility.

Previous studies have shown that both nuclear reprogramming as well as 'imprinting' are vital for the survival and later development of the embryo. However, the underlying mechanisms governing the intricate interplay of these two processes during the early embryonic phase have not been clear, until now.

Nuclear Reprogramming

Immediately after fertilisation, the majority of the 'epigenetic marks' on the DNA from the sperm and egg cells are erased. The erasure process, termed nuclear reprogramming, allows the genes from the parents to be reset so that the early embryonic cells can develop into any cell types of the body.

Genomic Imprinting

On the other hand, certain 'epigenetic marks' on a particular set of genes, some from the mother and some from the father must be preserved. These genes are said to be "imprinted" by their parent of origin and preservation of these marks is critical for the survival of the newly formed embryo. Expression of these imprinted genes at the appropriate levels ensures proper development of the embryo. If the 'epigenetic marks' on the 'imprinted' genes are not protected, severe and multiple developmental defects occur in the embryo.

Using genetically identical mice from an inbred mouse strain[2], Drs. Davor Solter and Barbara Knowles, Senior Principal Investigators at IMB, observed that none of the embryos resulting from the fertilisation of eggs lacking TRIM28 survived. The embryos died at varying stages of development, and had very different developmental defects. Given that most genetic diseases attributed to the lack of a single gene have consistently similar defects in every affected individual, the highly varied abnormalities observed in the maternal TRIM28-deficient, yet genetically identical mice, were peculiar.

To further elucidate these findings and the role of TRIM28 during nuclear reprogramming, Dr. Daniel Messerschmidt, the first author of this paper, collaborated with Dr. Anne Ferguson-Smith, a visiting Professor at A*STAR's Singapore Institute for Clinical Sciences (SICS), from the University of Cambridge, UK. Together, they conducted a comprehensive study on the epigenetic state and the level of expression of a group of imprinted genes known to be important for development. Using highly sophisticated microarray analysis and advanced biochemical techniques, they found that not only is the presence of TRIM28 protein important during this critical period, but the timing and amount of TRIM28 made available to the newly formed embryo greatly impacts the expression of these imprinted genes at later developmental stages.

Genomic imprinting was first described by Dr. Davor Solter at the Wistar Insitute and by Dr. Azim Surani at Cambridge University three decades ago. Recently, Dr Solter suggested that the interplay between nuclear reprogramming and genetic imprints could be explained by a simple analogy from school where the teacher writes a long string of formulas on the black board. At the end of the class he marks stretches to be preserved for the next day's lecture (these are the imprinted marks) and asks the cleaning lady to erase the rest (she performs the reprogramming).

Dr Solter said, "For the longest time, we didn't know why some bits of the formulas escaped erasure. Through this study, the mystery is finally revealed! We now know TRIM28 instructs the 'cleaning lady' which part of the formulas she should preserve."

Dr. Azim Surani, who was not involved in this study, said "This elegant study on TRIM28 provides significant mechanistic insights on how maternal factors in eggs ensure faithful epigenetic inheritance that plays a critical role during development. These findings are relevant not only for the widely practised in vitro fertilisation of eggs for the treatment of human infertility, but also more generally for highlighting the importance of epigenetic mechanisms in development and disease."

Dr. Barbara Knowles, the senior author of this paper said, "Lack of TRIM28 in their eggs could explain why some women consistently suffer from multiple failed pregnancies where embryos die at different time points, manifesting multiple, different abnormalities."

Prof Birgitte Lane, Executive Director of IMB, said, "Understanding the role of differential epigenetic modifications is important for the study of human diseases and development. This study has unravelled a critical component essential for nuclear reprogramming. The mechanistic insights revealed have far-reaching clinical implications for treatment of diseases with patient-specific cell therapies. This finding demonstrates how discoveries of fundamental research can shed light on biological questions to open new avenues of formulating therapeutic strategies for the benefits of patients."

Notes:

[1] Fertilisation in humans is the fusion of an egg with a sperm to produce an embryo, a new organism.

[2] Every mouse from an inbred strain is genetically identical (i.e. a twin) to every other mouse of the same strain. The inbred mouse strain used in this study originated from The Jackson Laboratory, where this study was initiated.


Story Source:

The above story is based on materials provided by Agency for Science, Technology and Research (A*STAR), Singapore. Note: Materials may be edited for content and length.


Journal Reference:

  1. D. M. Messerschmidt, W. de Vries, M. Ito, D. Solter, A. Ferguson-Smith, B. B. Knowles. Trim28 Is Required for Epigenetic Stability During Mouse Oocyte to Embryo Transition. Science, 2012; 335 (6075): 1499 DOI: 10.1126/science.1216154

Cite This Page:

Agency for Science, Technology and Research (A*STAR), Singapore. "Key component in mother's egg critical for survivial of newly formed embryo." ScienceDaily. ScienceDaily, 29 March 2012. <www.sciencedaily.com/releases/2012/03/120329101856.htm>.
Agency for Science, Technology and Research (A*STAR), Singapore. (2012, March 29). Key component in mother's egg critical for survivial of newly formed embryo. ScienceDaily. Retrieved September 23, 2014 from www.sciencedaily.com/releases/2012/03/120329101856.htm
Agency for Science, Technology and Research (A*STAR), Singapore. "Key component in mother's egg critical for survivial of newly formed embryo." ScienceDaily. www.sciencedaily.com/releases/2012/03/120329101856.htm (accessed September 23, 2014).

Share This



More Health & Medicine News

Tuesday, September 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Liberia Pleads for Help to Fight Ebola

Liberia Pleads for Help to Fight Ebola

AP (Sep. 22, 2014) Liberia's finance minister is urging the international community to quickly follow through on pledges of cash to battle Ebola. Bodies are piling up in the capital Monrovia as the nation awaits more help. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Ebola Doctor Says Border Controls Critical

Ebola Doctor Says Border Controls Critical

AP (Sep. 22, 2014) A Florida doctor who helped fight the expanding Ebola outbreak in West Africa says the disease can be stopped, but only if nations quickly step up their response and make border control a priority. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. Video provided by Newsy
Powered by NewsLook.com
Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins