Mathematical modelling of oxygen transport-limited follicle growth

Abstract

Mathematical modelling was used to investigate oxygen transport in the developing ovarian follicle. In contrast to previous findings, the results show that oxygen can reach the oocyte in large preantral follicles. This is largely due to the inclusion of fluid voidage in the model and improved estimates of oxygen diffusion coefficients through the granulosa. The results also demonstrate that preantral follicles will eventually reach a size beyond which further growth will result in the follicle becoming increasingly anoxic. The predicted size range at which this occurs is consistent with the size range at which antrum formation is observed in many mammals. This suggests that the antrum formation stage of follicular growth may be pivotal to the further development and ultimate fate of the follicle, and that antrum formation itself may represent a mechanism by which the follicle can overcome oxygen limitations. This was supported through extension of the model to the antral follicle, which showed that antrum formation can provide a way in which the follicle can continue to grow and yet avoid becoming hypoxic. The results of the model were consistent with observed follicle development.

Fibrin Encapsulation and Vascular Endothelial Growth Factor Delivery Promotes Ovarian Graft Survival in Mice

“…18,19 Efficient revascularization after tissue grafting contributed to the resumption of ovarian function and the longevity of the graft. For a metabolically active tissue such as the ovary, diffusion is limited to a couple hundred microns 35 and the presence of empty follicles in the grafts is believed to be a result of ischemia as was reported by Dolmans and colleagues. 36 Therefore, the survival of developing follicles is dependent on revascularization.…”

Microarray analysis of mRNA from cumulus cells following in vivo or in vitro maturation of mouse cumulus–oocyte complexes

“…indeed. may even be the stimulus for antral formation (Redding et al 2007(Redding et al , 2008. However, previously we have reported that HIF activity is not associated with follicular growth at any stage of mouse ovarian folliculogenesis, but is evident immediately following the ovulatory signal, associated with granulosa cell luteinisation (Tam et al 2010).…”

Metabolism throughout follicle and oocyte development in mammals

“…Predicted and actual measurements of oxygen concentration in antral follicles are similar to those in venous blood (Redding et al, 2008). Thus, the oxygen supply to the oocyte may only be limited at the late preantral to early antral stage and at the early preovulatory stage (Redding et al, 2007(Redding et al, , 2008. Follicle angiogenesis at these stages could be crucial for oocyte oxygen-ation and development (Van Blerkom, 2000).…”

“…When the growing follicle reaches a size at which supply from theca capillaries could be compromised, because of the thickening and nutritional requirements of the GC layer, the follicular fluid acts as a source of oxygen and nutrients (Redding et al, 2007). Mathematical modeling was used to study the mean oxygen concentration in human follicles; and predicted a low oxygen concentration within large preantral follicles, yet sufficient to reach the oocyte (Redding et al, 2007).…”

“…Mathematical modeling was used to study the mean oxygen concentration in human follicles; and predicted a low oxygen concentration within large preantral follicles, yet sufficient to reach the oocyte (Redding et al, 2007). Other studies in the human (Redding et al, 2008) and bovine (Clark and Stokes, 2011) predict a sharp rise in intrafollicular oxygen with antrum formation, peaking at the end of the early antral stage before decreasing through the antral to preovulatory stages, and to finally increase around the time of ovulation.…”