Species-specific differences in follicular antral sizes result from diffusion-based limitations on the thickness of the granulosa cell layer

Abstract

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>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 ∼45±10 µm. Based on the measured kinetic constants, the model reveals that the observed fall in the gonadotrophin 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 gonadotrophins. Larger animals (with a larger blood volume) require more estradiol as produced by the ovaries to down-regulate follicle-stimulating hormone-secretion in the pituitary. Larger follicle diameters result in larger follicle surface areas for constant granulosa layer thickness. The reported increase in the 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.

Regulation of Mammalian Oocyte Meiosis by Intercellular Communication Within the Ovarian Follicle

“…Among mammals, the size of the preovulatory follicle is proportional to the size of the animal, ranging in diameter from approximately 400 μm in a mouse to more than 10 cm in a rhinoceros (15). The diameter of a human preovulatory follicle is approximately 2 cm.…”

The hormonal composition of follicular fluid and its implications for ovarian cancer pathogenesis

“…Mature human follicles reach approximately 23 mm in diameter, yielding upwards of 5 mL of follicular fluid (FF) [13]. During ovulation, FF is released and bathes the surrounding tissue, including the ovarian surface epithelium and fallopian tube (FT) fimbria proximal to the ovary.…”

Follicular blood flow, antrum growth and angiogenic mediators in mares from ovulation to deviation

“…Follicular fluid derives mainly from plasma via the vascular component in the follicle wall (Fahiminiya and Gérard, 2010). The membrana granulosa receive their nutrients by diffusion from the vascularized theca and the antrum plays a role for determining the volume of the granulosa layer (Bächler et al, 2014).…”