The Ovarian Blood Follicle Barrier Is Both Charge- and Size-Selective in Mice1

This report characterizes the permeability and selectivity properties of the ovarian blood-follicle barrier. Proteins of similar size but opposite net charge possess strikingly different permeabilities with respect to this barrier. Inter-alpha-inhibitor (I alpha I, 220 kDa, pI approximately 6.2) is excluded from the follicle until an ovulatory stimulus, whereas immunoglobulin G (IgG, 155 kDa, pI approximately 6.5-7.0) passes into the follicle without an ovulatory stimulus. However, cationization of I alpha I results in its influx into the follicle in the absence of an ovulatory signal. Conversely, anionization of IgG results in its exclusion from the follicle unless an ovulatory stimulus (hCG administration) is provided. Molecular size also plays a role in blood-follicle barrier selectivity. For example, cationization of alpha 2-macroglobulin (pI approximately 8.5; 700 kDa) fails to facilitate its entry into unstimulated follicles. Conversely, negatively charged BSA (pl approximately 4.5; 66 kDa) passes freely into unstimulated follicles. These studies support the hypothesis that the blood-follicle barrier is size-selective but that charge sign and density play a role in the permeability of this barrier to proteins within an intermediate size range.