  The size of mature oocytes is similar across mammalian species, yet the size
of ovarian follicles increases with species size, with some ovarian follicles
reaching diameters more than 1000-fold the size of the enclosed oocyte. Here we
show that the different follicular sizes can be explained with diffusion-based
limitations on the thickness of the hormone-secreting granulosa layer. By
analysing published data on human follicular growth and granulosa cell
expansion during follicular maturation we find that the 4-fold increase of the
antral follicle diameter is entirely driven by an increase in the follicular
fluid volume, while the thickness of the surrounding granulosa layer remains
constant at about 45+/-10 mkm. Based on the measured kinetic constants, the
model reveals that the observed fall in the gonadotropin concentration from
peripheral blood circulation to the follicular antrum is a result of
sequestration in the granulosa. The model further shows that as a result of
sequestration, an increased granulosa thickness cannot substantially increase
estradiol production but rather deprives the oocyte from gonadotropins. Larger
animals (with a larger blood volume) require more estradiol as produced by the
ovaries to downregulate FSH-secretion in the pituitary. Larger follicle
diameters result in larger follicle surface areas for constant granulosa layer
thickness. The reported increase in follicular surface area in larger species
indeed correlates linearly both with species mass and with the predicted
increase in estradiol output. In summary, we propose a structural role for the
antrum in that it determines the volume of the granulosa layer and thus the
level of estrogen production.
