Inserm - Institut National de la santé et de la recherche médicale

09/12/2024 | News release | Distributed by Public on 09/12/2024 04:48

Marie-Émilie Terret: Unlocking the secrets of oocytes

Marie-Émilie Terret is an Inserm Research Director at the Centre for Interdisciplinary Research in Biology at Collège de France in Paris. She specialises in describing the particularities of oocytes, highly complex cells whose functioning is key to the viability of future embryos. Her scientific creativity and valuable multidisciplinary collaborations have led her to discover, to give just one example, an important marker of oocyte quality. A promising breakthrough in reproductive medicine.

Marie-Émilie Terret co-leads with Marie-Hélène Verlhac the Oocyte Mechanics and Morphogenesis team at the Centre for Interdisciplinary Research in Biology (unit 1050 Inserm/CNRS/Collège de France) in Paris. © Inserm/François Guénet

Oocytes-precursors of eggs-are very particular cells that dance to their own tune. Formed from the stage of embryogenesis, they are the oldest cells in the female body, along with neurons. Isolated in types of sacs called 'ovarian follicles', they are enormous in size, have no centrosomes-the pillars of cell architecture-and remain at an unfinished stage of development for a number of years. This is what attracts Terret and is why she has decided to dedicate her work to them. 'This highly original cell model raises questions of basic- but also applied research, given that oocytes become eggs that can produce embryos. Poor quality oocytes therefore compromise fertilisation and embryonic development', she explains.

It was the existence of these cells that convinced her to embark on a research career. 'Sometimes life paths hang on a thread. I owe my career as a researcher to a professor at the École Normale Supérieure in Lyon where I studied, who shared his passion for the subject and sparked this vocation within me. Then I was recruited for a Master's internship in a lab working on oocytes at Sorbonne University in 1999, and following that as a PhD student in 2000. The relevance of the research, but also the trust and freedom given to the teams to conduct their projects, convinced me that I was in the right place.' Terret then completed a postdoc on cancer cell division in the team led by Prasad Jallepalli at the Sloan Kettering Institute in New York. The deviation from her initial subject area led to something clicking into place. 'While this US experience was interesting, I only had one idea in mind: getting back to the oocytes!', she confides.

Shared research efforts

She then contacted her thesis laboratory at the Centre for Interdisciplinary Research in Biology to offer her services as a researcher and was immediately welcomed. 'I'm not driven by ego, I didn't want to set up my own team but rather to increase the expertise of this oocyte "super laboratory" with new project ideas.' In 2017, she became co-leader, together with Marie-Hélène Verlhac, of the Oocyte Mechanics and Morphogenesis team: an atypical status at the time. 'Co-leaderships were less common than now, but it made sense so that we could pool our skills, resources and numerous collaborations with hospital doctors, physicians and specialists in artificial intelligence.'

Since then, Terret can be delighted to have already significantly enriched our knowledge of these female cells. 'The long-term goal is to provide tools for reproductive medicine in the context of oocytes preservation and assisted reproductive technologies, to improve their outcomes', she recalls. To understand these advances, we need to go back to the basics of the oocytes themselves, of which girls are born with all they will ever have. However, the development of these cells is suspended for a number of years before resuming on a cyclical basis from adolescence until menopause, with the aim of becoming a fertilisable egg with a single set of chromosomes. This stage completes the meiosis, enabling the egg to have half as much genetic material as the body's other cells, in anticipation of meeting a sperm cell which also contains its own half. Terret is studying this mechanism, which in some cases is dysfunctional, as well as the formation of the embryo from the oocyte. 'The sperm only provides DNA while the egg provides everything else: proteins, RNA, mitochondria and other cell compartments, she recalls. We want to understand what a good quality egg is and how it turns into a viable embryo.'

A patented discovery

In addition to describing several mechanisms associated with abnormal oocyte development, she has discovered the importance of their mechanical properties. 'The level of rigidity of the cell, its ability to deform or not, is crucial for oocytes and embryos to have the right number of chromosomes and balanced cell content, she explains. It's a true high-quality biomarker that could be used in the clinical setting. As such, we're developing a microfluidic device to measure the mechanical resistance of oocytes, in combination with an artificial intelligence program that evaluates the quality of the intracellular medium. We have filed a patent.'

While this breakthrough is important in her career as a researcher, Terret is aware of the ground that needs to be covered in order to unlock the secrets of oocytes. To do this, she is counting on 'scientific creativity'. 'That's what I like about this job: inventing, being daring, being unafraid to test ideas that may seem off-the-wall at first. And that's what I pass on to the students I hire in the lab (doctoral students, post-docs, technical staff, etc.). I really like supporting them with their research project or training, but also, more broadly, helping them in their choices of direction. Doing so contributes greatly to my professional development.' A commitment that earned her the 2023 Nature Award for Mentoring in Science for which she was put forward by her students-a sign of mutual recognition.

Marie-Émilie Terret co-leads with Marie-Hélène Verlhac the Oocyte Mechanics and Morphogenesis team at the Centre for Interdisciplinary Research in Biology (unit 1050 Inserm/CNRS/Collège de France) in Paris.