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The development of ovarian follicles is a unique instance of a morphogenesis process still occurring during adult life and resulting from the interactions between somatic and germ cells. In mammals, the initiation of follicular development from the pool of resting follicles is characterized by an increase in the oocyte size concomitant with the surrounding somatic cells proliferating to build an avascular tissue called granulosa. We present a stochastic individual-based model describing the first stages of follicular development, where the cell population is structured with respect to age (progression within the cell cycle) and space (radial distance from the oocyte). The model accounts for the molecular dialogue existing between the oocyte and granulosa cells. Three dynamically interacting scales are considered in the model: (i) a microscopic, local scale corresponding to an individual cell embedded in its immediate environment, (ii) a mesoscopic, semi-local scale corresponding to anatomical or functional areas of follicles and (iii) a macroscopic, global scale corresponding to the morphology of the follicle. Numerical simulations are performed to reproduce the 3D morphogenesis of follicles and follow simultaneously the detailed spatial distribution of individual granulosa cells, their organization as concentric layers or functional cell clones and the increase in the follicle size. Detailed quantitative simulation results are provided in the ovine species, in which well characterized genetic mutations lead to a variety of phenotypic follicle morphogenesis. The model can help to explain pathological situations of imbalance between oocyte growth and follicular cell proliferation 1. Introduction. A highly efficient reproductive capacity is a major advantage for species preservation, faced with the natural selection process, and for individuals within species. In mammalian females, ovarian function is the subject of intensive investigations with the aim to improve the reproductive capacity of domestic and wild animal species and to treat ovarian failures leading to infertility in humans. The issues are crucial for both clinical and zootechnical applications. In humans, the prevalence of the polycystic ovarian syndrome, which is a main cause of infertility, has been estimated at up to 10% among reproductive-age women [19]. Improvement of reproductive biotechnologies, including in vitro fertilization, intra-cytoplasmic sperm injection, frozen embryo replacements and egg donation, is a key issue for a better management of reproduction. Improving the knowledge upon ovarian function and its control will help to improve the success of assisted reproductive technologies, hence to prevent ovarian failure or hyperstimulation syndrome in women and to manage

Coupled Somatic Cell Kinetics and Germ Cell Growth: Multiscale Model-Based Insight on Ovarian Follicular Development