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

30 Dec

Size-Selective in Mice

The developing ovarian follicle is composed of an avascular fluid-filled antrum containing the oocyte, and a highly vascularized thecal compartment located external to the follicular basement membrane (membrana propria). The follicular fluid contributes to an environment within the avascular compartment that supports follicular development. The specialized antral environment is created not only by secretions from membrana granulosa but by serum proteins, which enter the follicular fluid in the avascular antrum by passing from the vasculature through the membrana propria.

The entrance of these proteins and the creation of the follicular environment are dependent on the regulation of a proposed blood-follicle barrier. Over thirty years ago several studies demonstrated the presence of a blood-follicle barrier in the mammalian ovary. Microscopic analysis with nonphysiological tracers (i.e., colloidal gold and Evan’s Blue dye) as well as comparative analysis of protein concentrations in follicular fluid and serum led to the suggestion that the barrier acted like a molecular sieve. The barrier was found to be permeable only to proteins under 500 kDa in size, and anything larger remained in the serum. Recently, our laboratory has provided physiological evidence for the existence and regulation of this barrier. We have found that serum glycoproteins of the inter-a-trypsin-inhibitor family are present in the follicular fluid only after an ovulatory surge (i.e., a natural gonadotropic surge or hCG administration). buy asthma inhaler
Inter-а inhibitor (lal, 220 kDa) and pre-a trypsin inhibitor (Pal, 130 kDa) possess a net negative charge and are synthesized in the liver and found in high concentrations in human blood (0.5 mg/ml). The charge of these and other proteins is determined by the pi, which is defined as the pH value of the isoelectric point (i.e., lal ~6.2). Within minutes after an ovulatory surge, a nitric oxide-triggered vasodilation increases blood flow and allows these proteins to enter the nonvascularized follicular compartment. Once inside the developing follicle, lal and Pal are covalently linked to newly synthesized hyaluronic acid, resulting in stabilization of the cumulus extracellular matrix. This stabilization leads to cumulus expansion and eventually to normal extrusion of the cumulus oocyte complex at ovulation.