Multi-scale modeling of the follicle selection process in the ovary

The biological meaning of follicular development is to free fertilizable oocytes at the time of ovulation. The ovulation rate results from an FSH-dependent follicle selection process. In this paper, we designed a multi-scale model of follicular development, where selection arises from the endocrine feedback between the ovaries and pituitary gland and appeals to control theory concepts. Each ovarian follicle is described through a 2D density function giving an age and maturity-structured description of its cell population. The control intervenes in the velocity, gain and loss terms of the conservation law ruling the changes in the density. The model accounts for the changes in the total cell number, growth fraction and global maturity of both ovulatory and degenerating follicles for various intensities of the selection rate. The different selection process outputs (mono- or poly-ovulation, anovulation) predicted by the model are consistent with physiological knowledge regarding vascularization, pituitary sensitivity to ovarian feedback and treatment with exogenous FSH.