Distribution of extracellular matrix proteins type I collagen, type IV collagen, fibronectin, and laminin in mouse folliculogenesis

Abstract

The extracellular matrix (ECM) plays a prominent role in ovarian function by participating in processes such as cell migration, proliferation, growth, and development. Although some of these signaling processes have been characterized in the mouse, the relative quantity and distribution of ECM proteins within developing follicles of the ovary have not been characterized. This study uses immunohistochemistry and real-time PCR to characterize the ECM components type I collagen, type IV collagen, fibronectin, and laminin in the mouse ovary according to follicle stage and cellular compartment. Collagen I was present throughout the ovary, with higher concentrations in the ovarian surface epithelium and follicular compartments. Collagen IV was abundant in the theca cell compartment with low-level expression in the stroma and granulosa cells. The distribution of collagen was consistent throughout follicle maturation. Fibronectin staining in the stroma and theca cell compartment increased throughout follicle development, while staining in the granulosa cell compartment decreased. Heavy staining was also observed in the follicular fluid of antral follicles. Laminin was localized primarily to the theca cell compartment, with a defined ring at the exterior of the follicular granulosa cells marking the basement membrane. Low levels of laminin were also apparent in the stroma and granulosa cell compartment. Taken together, the ECM content of the mouse ovary changes during follicular development and reveals a distinct spatial and temporal pattern. This understanding of ECM composition and distribution can be used in the basic studies of ECM function during follicle development, and could aid in the development of in vitro systems for follicle growth.

Oestrogen formation and connective tissue growth factor expression in rat granulosa cells

“…We previously proposed that granulosa-derived CTGF is one of the main signals for formation of the thecal compartment when follicles form and begin to grow. A continuing role for CTGF in the extensive thecal remodelling required during antral stages of follicular development seems equally likely, particularly in light of the recent finding that key ECM markers, such as collagen IV and fibronectin appear to be developmentally regulated in the mouse follicle (Berkholtz et al 2006). In this connection, CTGF is implicated in the deposition of collagen, through its role in modulating lysyl oxidase (Hong et al 1999), a crucial enzyme required for cross-linking of collagen monomers (Smith-Mungo & Kagan 1998).…”

“…Ovarian CTGF immunoreactivity has previously only been observed in the pig (Wandji et al 2000), where it paralleled mRNA expression in granulosa, theca and vascular endothelial cells of the theca and corpus luteum. Several ECM components have been characterised during mouse follicular development (Berkholtz et al 2006). For example, fibronectin and type IV collagen are detectable in theca, stroma and basement membrane of small preantral (SP) follicles and increase as the follicle size increases (Berkholtz et al 2006).…”

“…Several ECM components have been characterised during mouse follicular development (Berkholtz et al 2006). For example, fibronectin and type IV collagen are detectable in theca, stroma and basement membrane of small preantral (SP) follicles and increase as the follicle size increases (Berkholtz et al 2006). Thus, based on the pattern of CTGF expression during folliculogenesis in rat (Slee et al 2001, Harlow et al 2002, luteal development in pig (Wandji et al 2000) and ECM component expression during mouse follicle development (Berkholtz et al 2006), granulosa cell-derived CTGF likely plays a critical role in theca cell recruitment, follicle growth and corpus luteum vascularisation.…”

Live births from isolated primary/early secondary follicles following a multistep culture without organ culture in mice

“…Naturally occurring extracellular matrices such as fibronectin, laminin, and collagen are deposited in ovarian follicles during follicle development. These matrices have important functions in a stage-specific manner (Berkholtz et al 2006). In this study, we focused on collagen gel, because collagen has been reported to stimulate cell growth and development in various mammalian cell culture systems (Wicha et al 1979, Yang et al 1980, Yang & Nandi 1983.…”

Formation of multiple-oocyte follicles in culture

“…This discriminatory divider is comprised mainly of collagen and laminin (Rodgers et al 1999;Berkholtz et al 2006) and allows only molecules of a certain size and charge to cross (Hess et al 1998). The FBL changes with the developing follicle, adapting its permeability and constituent molecules.…”