NCBI Summary:
This gene encodes one of the six subunits of type IV collagen, the major structural component of basement membranes. Mutations in this gene are associated with X-linked Alport syndrome, also known as hereditary nephritis. Like the other members of the type IV collagen gene family, this gene is organized in a head-to-head conformation with another type IV collagen gene so that each gene pair shares a common promoter. Three transcript variants have been identified for this gene.
General function
Cell adhesion molecule
Comment
Cellular localization
Extracellular Matrix, Secreted
Comment
Ovarian function
Comment
Collagens in the human ovary and their changes in the perifollicular stroma during ovulation. Lind AK et al. BACKGROUND: Remodeling of the collagens around the follicle is a major event in ovulation. The aim of the present study was to investigate the distribution of collagen I, III, and IV in the human ovary. METHODS: Biopsies of the perifollicular stroma were obtained at sterilization during the preovulatory phase (follicle size >14 mm) or at any of three intervals (12-18 h after human chorionic gonadotrophin: early ovulatory phase; >18-24 h: late ovulatory phase; 44-77 h: postovulatory phase) after human chorionic gonadotrophin. Excised dominant follicles and whole ovarian sections were also obtained. Immunohistochemistry using antibodies against collagen I, III, IV, vimentin, and CD 45 was performed. RESULTS AND CONCLUSIONS: Collagens I and III were distributed in concentric layers in the capsular stroma with bundles of collagens connecting these layers to form a mesh. Collagen I was present in larger quantities in the outer layers and collagen III showed the inverse distribution. In the theca, collagen I was present in the externa and collagen III in the entire layer. The staining intensity of collagens I and III in the perifollicular stroma decreased from the preovulatory stage. Collagen IV was present in the basal lamina separating granulosa and theca cells. This study shows that collagen I and III are abundant in and around the ovulating human follicle with typical patterns of distribution. Collagen IV is present in the basal membrane that separates the granulosa from the theca cells. Taking into account the abundance of collagens in the follicular wall and their specific localization, major site-directed degradation of collagens seems to be necessary for follicular rupture to occur.
Expression regulated by
FSH
Comment
This gene is FSH induced. Identification of differential gene expression in in vitro FSH treated pig granulosa cells using suppression subtractive hybridization. Bonnet A et al. ABSTRACT: FSH, which binds to specific receptors on granulosa cells in mammals, plays a key role in folliculogenesis. Its biological activity involves stimulation of intercellular communication and upregulation of steroidogenesis, but the entire spectrum of the genes regulated by FSH has yet to be fully characterized. In order to find new regulated transcripts, however rare, we have used a Suppression Subtractive Hybridization approach (SSH) on pig granulosa cells in primary culture treated or not with FSH. Two SSH libraries were generated and 76 clones were sequenced after selection by differential screening. Sixty four different sequences were identified, including 3 novel sequences. Experiments demonstrated the presence of 25 regulated transcripts. A gene ontology analysis of these 25 genes revealed (1) catalytic; (2) transport; (3) signal transducer; (4) binding; (5) anti-oxidant and (6) structural activities. These findings may deepen our understanding of FSH's effects. Particularly, they suggest that FSH is involved in the modulation of peroxidase activity and remodelling of chromatin.
Ovarian localization
Theca
Comment
Distribution of extracellular matrix proteins type I collagen, type IV collagen, fibronectin, and laminin in mouse folliculogenesis. Berkholtz CB et al. 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.
Follicle stages
Comment
The distribution of type IV collagen alpha chains in the mouse ovary and its correlation with follicular development. Nakano K et al. The present study aims to identify alpha chains of type IV collagen in the basement membrane of the mouse ovarian follicle and examine their changes during follicular development using immunofluorescence microscopy with specific monoclonal antibodies. The basement membrane of the serous mesothelium enveloping the ovary contained all alpha chains of type IV collagen, alpha1(IV) through alpha6(IV) chains. Primordial follicles showed a distinct immunoreactivity against all six alpha chains in their basement membranes. Immunolabeling for alpha3(IV) and alpha4(IV) chains was almost eliminated in the primary follicles. In basement membranes of secondary and Graafian follicles, the immunofluorescent reaction of alpha3(IV) and alpha4(IV) chains disappeared in Graafian follicles, a partial reduction in fluorescent immunostaining intensity to alpha5(IV) and alpha6(IV) chains was observed; only alpha1(IV) and alpha2(IV) chains were not degraded throughout follicular development. On atretic follicles, in addition to alpha1(IV) and alpha2(IV) chains, alpha3(IV), alpha4(IV), alpha5(IV) and alpha6(IV) chains frequently persisted. A basement membrane-like matrix within the follicular granulosa cell layer, such as the focimatrix (focal intraepithelial matrix) and/or Call-Exner body, was also recognized in mouse secondary and Graafian follicles and contained alpha1(IV), alpha2(IV), alpha5(IV) and alpha6(IV) chains but not alpha3(IV) and alpha4(IV) chains. We expect that the decrease in alpha(IV) chains prompts follicular development and is a prerequisite condition for follicular maturation.