The extracellular matrix (ECM) promotes and/or inhibits many cellular processes, including but not limited to proliferation, differentiation, and survival, which must occur for follicle growth and oocyte maturation. The ECM regulation of cellular processes in ovarian cells is being investigated in many animal models, including avian, rat, bovine, porcine, rabbit, sheep, human, and mouse. Granulosa cells are more frequently employed; however, the culture of intact follicles and ovaries has been developed and enables ECM functions in folliculogenesis to be studied. ECMcomponents that have been examined are used individually (collagen, laminin, fibronectin) or collectively (Matrigel, isolated basal lamina, and ECM produced by cell lines) in both two-and three-dimensional model systems. In granulosa cell cultures, ECM affects morphology, aggregation and communication, survival, proliferation, and steroidogenesis; whereas follicle and ovary cultures demonstrate a regulation of folliculogenesis. This article describes the ECM functionality on ovarian cells throughout development, and highlights the potential of developing technologies to identify structure-function relationships in follicle maturation.
KeywordsExtracellular matrix; granulosa cells; morphology; proliferation; survival Ovarian follicle development is regulated by endocrine, paracrine, and autocrine factors in a spatially and temporally regulated manner, and is characterized by dramatic changes throughout maturation. The ovary contains a large reserve of inactive primordial follicles arrested in prophase I, with a small cohort activated daily. Prior to activation, these immature follicles contain nongrowing oocytes and nondividing, flattened (squamous) pregranulosa cells surrounded by a basal lamina. Following activation, follicle growth begins with the transformation of squamous pregranulosa cells into a single layer of cuboidal granulosa cells surrounding a growing oocyte. Granulosa cells proliferate to form multiple layers, requiring expansion of the basal lamina, and leading to two-layered and multilayered follicle stages. At this time, an outer layer of cells, termed the theca layer, is recruited (or differentiated from existing stroma 1 ) and surrounds the basal lamina. A fluid-filled antral cavity, or antrum, forms in the granulosa cell compartment of the follicle later in folliculogenesis. Small antral follicles develop into mature preovulatory follicles in the presence of follicle-stimulating hormone