CIRB - Équipe de recherche

Oocyte Mechanics and Morphogenesis

Mécanique et morphogenèse de l'ovocyte

Principal Investigators: Marie-Emilie TERRET, DR2 INSERM & Marie-Hélène Verlhac, DRCE2 CNRS

Présentation

At fertilization, the sperm mostly transmit their genome but oocytes are transmitted in full to the next generation. Using cell biology, genetics, computational biology and biophysics approaches of meiotic divisions, we study the nature of this maternal inheritance, its transmission, and the consequences when it goes awry.

In the human species, female gamete production is error-prone, generating a high basal rate of poor-quality oocytes (10-20%) increasing with the mother's age, leading to infertility, miscarriage and congenital syndromes such as trisomies. This is a public health problem in our modern world, where women tend to delay the age of their first pregnancy, reflecting societal changes. A direct consequence is that oocyte freezing for fertility preservation and the use of ART (Assisted Reproductive Technologies) increases worldwide, yet only 20% of ART cycles result in a birth. Gamete quality is a key parameter for it success rate. However, contrary to sperm, no biomarker exists to evaluate oocyte quality in ART. An important fundamental question is therefore to define what oocyte quality is, in order to be able to recognize it. In other words, what is the nature of the information contained in the oocyte that shapes its quality and enables the formation of a new individual? While the sperm mostly transmit their genome at fertilization, oocytes are transmitted in full to the next generation, suggesting that oocyte quality is determined not only by its genome, but also by its large cytoplasm. To explore this maternal inheritance, we study the last stages of mammalian oogenesis, namely the end of oocyte growth followed by meiotic divisions, and early embryonic development (Fig 1).

Scheme of the main steps of the last stages of oocyte development in mammals
Fig 1: Scheme of the main steps of the last stages of oocyte development in mammals. During their growth in the ovary, oocytes are arrested in Prophase I of meiosis. After puberty and cyclically, some resume meiosis (NEBD Nuclear Envelope BreakDown) and undergo two successive very asymmetric meiotic divisions in size, with the production of two small polar bodies (PB) once fertilized, and a one-cell embryo called zygote harboring the same size as the oocyte in Prophase I. The steps from Prophase I, where oocytes present a nucleus, to Metaphase II (MII) can be reproduced in vitro for both mouse and human oocytes. MII oocytes can be fertilized and early embryonic development follows.