Remodeling of extracellular matrix at ovulation of the bovine ovarian follicle

Abstract

Using immunohistochemistry and RNA analyses we examined the fate of components of a newly identified matrix that develops between granulosa cells (focimatrix, abbreviated from focal intraepithelial matrix) and of the follicular basal lamina in ovulating bovine ovarian follicles. Pre- and postovulatory follicles were generated by treatment with estradiol (Day 1), progesterone (Days 1-10), and prostaglandin analogue (Day 9) with either no further treatment (Group 1, n = 6) and or with 25 mg porcine LH (Day 11, Group 2, n = 8 or Day 10, Group 3, n = 8) and ovariectomy on Day 12 (12-14 hr post LH in Group 2, 38-40.5 hr in Group 3). In the time frame examined no loss of follicular basal lamina laminin chains beta2 and gamma1 or nidogen 1 was observed. In the follicular basal lamina collagen type IV alpha1 and perlecan were present prior to ovulation; after ovulation collagen type IV alpha1 was discontinuously distributed and perlecan was absent. Versican in the theca interna adjacent to the follicular basal lamina in preovulatory follicles was not observed post ovulation, however, the granulosa cells then showed strong cytoplasmic staining for versican. Expression of versican isoforms V0, V1, and V3 was detected at all stages. Focimatrix was observed in preovulatory follicles. It contained collagen type IV alpha1, laminins beta2 and gamma1, nidogen 1 and perlecan and underwent changes in composition similar to that of the follicular basal lamina. In conclusion focimatrix and the follicular basal lamina are degraded at ovulation. Individual components are lost at different times.

Angiogenesis and vascular function in the ovary

“…Heparanase is an endoglycosidase that cleaves polymeric heparan sulphate molecules from large HSPG. It was recently demonstrated that LH stimulated a rapid increase in heparanase mRNA and protein concentrations in the bovine granulosa cells (Klipper et al 2009) and this could explain the disappearance of perlecan from collapsed follicles shortly after ovulation (Irving-Rodgers et al 2006). This would then stimulate the release of sequestered factors such as FGF2 and heparan sulphates, thereby facilitating endothelial invasion.…”

“…It is curious that the accumulation of VEGFA in the granulosa is unable to stimulate protease activity and enable the migration of endothelial cells into the granulosa layer. This is presumably due to the more complex composition of the follicular basement membrane (mainly collagen type IV, laminin a1, b1 and b2 as well as nidogen, perlecan and focimatrix), while the ECM associated with the vasculature is principally composed of collagen IV and laminin b2 (Irving- Rodgers et al 2006).…”

“…Perlecan is a large heparan sulphate proteoglycan (HSPG) that is a major constituent of both the follicular basal lamina and focimatrix that has been located between granulosa cells (Irving-Rodgers et al 2006). It can sequester a number of angiogenic growth factors including FGF2.…”

Studies of granulosa cell maturation in dominant and subordinate bovine follicles: novel extracellular matrix focimatrix is co-ordinately regulated with cholesterol side-chain cleavage CYP11A1

“…Focimatrix in the cow is composed of aggregates of basal lamina material (collagen type IV a-1 (COL4A1) and a-2, laminin chains a-1, b-2 (LAMB2) and g-1, perlecan (HSPG2), and nidogens 1 and 2 (NID1 and -2). It is degraded at ovulation (Irving- Rodgers et al 2006a) as granulosa cells commence terminal differentiation into luteal cells and hence does not exist in human or bovine corpora lutea (Irving- Rodgers et al 2004Rodgers et al , 2006b. Thus, focimatrix is developmentally regulated and is present before, and then during, the follicular phase when granulosa cells mature to produce progesterone and oestradiol and at the same time when follicles become dominant or subordinate.…”

Review on Ovarian Cryopreservation in Large Animals and Non-Human Primates

“…The function (Yang&Fortune, 2006) and the structure (Rodgers&Irving- Rodgers, 2010) of the bovine ovary has been extensively studied. Also, the granulosa cells and the extracellular matrix of bovine follicles of various developmental stages are well described (Lavranos et al, 1994;Irving-Rodgers et al, 2006).…”