Abstract
The ovarian follicle contains several different cell types and separate compartments and undergoes substantial development during its growth and maturation. Extracellular matrix (ECM) could be expected to play a major role in these processes. Most research on ECM in follicles has focused on the follicular basal lamina and its changing composition during folliculogenesis and on the specialised matrix formed at ovulation by the cumulus cells surrounding the oocyte and the zona pellucida. We review these aspects. Few naturally occurring gene mutations have identified unique roles for ECM molecules in follicular function. Presumably, any mutations leading to reduced fertility are eliminated quickly by natural selection and, when mutations are not eliminated, considerable redundancy occurs to ensure successful reproduction. In mice, in which the genome can be easily manipulated, the modification of matrix components associated with cumulus and oocytes has often resulted in partial infertility, suggesting redundancy. We provide an update of basal lamina components focusing on newer discoveries. In addition, we review matrix associated with the occyte and cumulus cells (excluding the zona pellucida) and other components of ECM. Where possible, we examine evidence for the role of the ECM in follicular development and diseases.
Similar content being viewed by others
References
Abrahamson DR (1986) Recent studies on the structure and pathology of basement membranes. J Pathol 149:257–278
Atiomo WU, Hilton D, Fox R, Lee D, Shaw S, Friend J, Wilkin TJ, Prentice AG (2000) Immunohistochemical detection of plasminogen activator inhibitor-1 in polycystic ovaries. Gynecol Endocrinol 14:162–168
Bagavandoss P, Sage EH, Vernon RB (1998) Secreted protein, acidic and rich in cysteine (SPARC) and thrombospondin in the developing follicle and corpus luteum of the rat. J Histochem Cytochem 46:1043–1049
Barber AJ, Lieth E (1997) Agrin accumulates in the brain microvascular basal lamina during development of the blood-brain barrier. Dev Dyn 208:62–74
Bornstein P, Sage EH (2002) Matricellular proteins: extracellular modulators of cell function. Curr Opin Cell Biol 14:608–616
Bradshaw AD, Graves DC, Motamed K, Sage EH (2003a) SPARC-null mice exhibit increased adiposity without significant differences in overall body weight. Proc Natl Acad Sci U S A 100:6045–6050
Bradshaw AD, Puolakkainen P, Dasgupta J, Davidson JM, Wight TN, Helene Sage E (2003b) SPARC-null mice display abnormalities in the dermis characterized by decreased collagen fibril diameter and reduced tensile strength. J Invest Dermatol 120:949–955
Carrette O, Nemade RV, Day AJ, Brickner A, Larsen WJ (2001) TSG-6 is concentrated in the extracellular matrix of mouse cumulus oocyte complexes through hyaluronan and inter-alpha-inhibitor binding. Biol Reprod 65:301–308
Chang RJ, Nakamura RM, Judd HL, Kaplan SA (1983) Insulin resistance in nonobese patients with polycystic ovarian disease. J Clin Endocrinol Metab 57:356–359
Chen L, Zhang H, Powers RW, Russell PT, Larsen WJ (1996) Covalent linkage between proteins of the inter-alpha-inhibitor family and hyaluronic acid is mediated by a factor produced by granulosa cells. J Biol Chem 271:19409–19414
Curry TE Jr, Osteen KG (2003) The matrix metalloproteinase system: changes, regulation, and impact throughout the ovarian and uterine reproductive cycle. Endocr Rev 24:428–465
Davis BJ, Lennard DE, Lee CA, Tiano HF, Morham SG, Wetsel WC, Langenbach R (1999) Anovulation in cyclooxygenase-2-deficient mice is restored by prostaglandin E2 and interleukin-1beta. Endocrinology 140:2685–2695
Duffy DM, Stouffer RL (2001) The ovulatory gonadotrophin surge stimulates cyclooxygenase expression and prostaglandin production by the monkey follicle. Mol Hum Reprod 7:731–739
Dunaif A (1995) Hyperandrogenic anovulation (PCOS): a unique disorder of insulin action associated with an increased risk of non-insulin-dependent diabetes mellitus. Am J Med 98:33S–39S
Dziadek M, Paulsson M, Timpl R (1985) Identification and interaction repertoire of large forms of the basement membrane protein nidogen. EMBO J 4:2513–2518
Eggli PS, Graber W (1993) Ultrastructural distribution of hyaluronan in rat cornea. Exp Eye Res 56:693–699
Elvin JA, Clark AT, Wang P, Wolfman NM, Matzuk MM (1999) Paracrine actions of growth differentiation factor-9 in the mammalian ovary. Mol Endocrinol 13:1035–1048
Fries E, Kaczmarczyk A (2003) Inter-alpha-inhibitor, hyaluronan and inflammation. Acta Biochim Pol 50:735–742
Fulop C, Salustri A, Hascall VC (1997) Coding sequence of a hyaluronan synthase homologue expressed during expansion of the mouse cumulus-oocyte complex. Arch Biochem Biophys 337:261–266
Fulop C, Szanto S, Mukhopadhyay D, Bardos T, Kamath RV, Rugg MS, Day AJ, Salustri A, Hascall VC, Glant TT, Mikecz K (2003) Impaired cumulus mucification and female sterility in tumor necrosis factor-induced protein-6 deficient mice. Development 130:2253–2261
Gilmour DT, Lyon GJ, Carlton MB, Sanes JR, Cunningham JM, Anderson JR, Hogan BL, Evans MJ, Colledge WH (1998) Mice deficient for the secreted glycoprotein SPARC/osteonectin/BM40 develop normally but show severe age-onset cataract formation and disruption of the lens. EMBO J 17:1860–1870
Groffen AJ, Ruegg MA, Dijkman H, van de Velden TJ, Buskens CA, van den Born J, Assmann KJ, Monnens LA, Veerkamp JH, van den Heuvel LP (1998) Agrin is a major heparan sulfate proteoglycan in the human glomerular basement membrane. J Histochem Cytochem 46:19–27
Hasan S, Hosseini G, Princivalle M, Dong JC, Birsan D, Cagide C, de Agostini AI (2002) Coordinate expression of anticoagulant heparan sulfate proteoglycans and serine protease inhibitors in the rat ovary: a potent system of proteolysis control. Biol Reprod 66:144–158
Hay E (1991) Cell biology of extracellular matrix. Plenum, New York
Holland PW, Harper SJ, McVey JH, Hogan BL (1987) In vivo expression of mRNA for the Ca++−binding protein SPARC (osteonectin) revealed by in situ hybridization. J Cell Biol 105:473–482
Huynh MH, Sodek K, Lee H, Ringuette M (2004) Interaction between SPARC and tubulin in Xenopus. Cell Tissue Res 317:313–317
Iozzo RV (1999) The biology of the small leucine-rich proteoglycans. Functional network of interactive proteins. J Biol Chem 274:18843–18846
Irving-Rodgers HF, Rodgers RJ (2000) Ultrastructure of the basal lamina of bovine ovarian follicles and its relationship to the membrana granulosa. J Reprod Fertil 118:221–228
Irving-Rodgers HF, Mussard ML, Kinder JE, Rodgers RJ (2002) Composition and morphology of the follicular basal lamina during atresia of bovine antral follicles. Reproduction 123:97–106
Irving-Rodgers HF, Harland ML, Rodgers RJ (2004) A novel basal lamina matrix of the stratified epithelium of the ovarian follicle. Matrix Biol 23:207–217
Ishiguro K, Kojima T, Taguchi O, Saito H, Muramatsu T, Kadomatsu K (1999) Syndecan-4 expression is associated with follicular atresia in mouse ovary. Histochem Cell Biol 112:25–33
Joyce IM, Pendola FL, O'Brien M, Eppig JJ (2001) Regulation of prostaglandin-endoperoxide synthase 2 messenger ribonucleic acid expression in mouse granulosa cells during ovulation. Endocrinology 142:3187–3197
Kobayashi H, Sun GW, Terao T (1999) Immunolocalization of hyaluronic acid and inter-alpha-trypsin inhibitor in mice. Cell Tissue Res 296:587–597
Kroger S, Schroder JE (2002) Agrin in the developing CNS: new roles for a synapse organizer. News Physiol Sci 17:207–212
Langenbach R, Morham SG, Tiano HF, Loftin CD, Ghanayem BI, Chulada PC, Mahler JF, Lee CA, Goulding EH, Kluckman KD, et al (1995) Prostaglandin synthase 1 gene disruption in mice reduces arachidonic acid-induced inflammation and indomethacin-induced gastric ulceration. Cell 83:483–492
Lees GE, Helman RG, Kashtan CE, Michael AF, Homco LD, Millichamp NJ, Ninomiya Y, Sado Y, Naito I, Kim Y (1998) A model of autosomal recessive Alport syndrome in English cocker spaniel dogs. Kidney Int 54:706–719
Li Q, Olsen BR (2004) Increased angiogenic response in aortic explants of collagen XVIII/endostatin-null mice. Am J Pathol 165:415–424
Lim H, Paria BC, Das SK, Dinchuk JE, Langenbach R, Trzaskos JM, Dey SK (1997) Multiple female reproductive failures in cyclooxygenase 2-deficient mice. Cell 91:197–208
Liu J, Carriere PD, Dore M, Sirois J (1997) Prostaglandin G/H synthase-2 is expressed in bovine preovulatory follicles after the endogenous surge of luteinizing hormone. Biol Reprod 57:1524–1531
Liu YX, Liu K, Feng Q, Hu ZY, Liu HZ, Fu GQ, Li YC, Zou RJ, Ny T (2004) Tissue-type plasminogen activator and its inhibitor plasminogen activator inhibitor type 1 are coordinately expressed during ovulation in the rhesus monkey. Endocrinology 145:1767–1775
Martinez-Hernandez A, Amenta PS (1983) The basement membrane in pathology. Lab Invest 48:656–677
McArthur ME, Irving-Rodgers HF, Byers S, Rodgers RJ (2000) Identification and immunolocalization of decorin, versican, perlecan, nidogen, and chondroitin sulfate proteoglycans in bovine small-antral ovarian follicles. Biol Reprod 63:913–924
Mittaz L, Russell DL, Wilson T, Brasted M, Tkalcevic J, Salamonsen LA, Hertzog PJ, Pritchard MA (2004) Adamts-1 is essential for the development and function of the urogenital system. Biol Reprod 70:1096–1105
Mukhopadhyay D, Asari A, Rugg MS, Day AJ, Fulop C (2004) Specificity of the tumor necrosis factor-induced protein 6-mediated heavy chain transfer from inter-alpha-trypsin inhibitor to hyaluronan: implications for the assembly of the cumulus extracellular matrix. J Biol Chem 279:11119–11128
Norose K, Clark JI, Syed NA, Basu A, Heber-Katz E, Sage EH, Howe CC (1998) SPARC deficiency leads to early-onset cataractogenesis. Investig Ophthalmol Vis Sci 39:2674–2680
Ny T, Peng XR, Ohlsson M, Hsueh AJ (1993) Hormonal regulation of the fibrinolytic components in the ovary. Transient and cell-specific expression of tissue-type plasminogen activator and plasminogen-activator-inhibitor type 1 results in controlled and directed proteolysis during gonadotropin-induced ovulation. Thromb Res 71:1–45
Ochsner SA, Russell DL, Day AJ, Breyer RM, Richards JS (2003) Decreased expression of tumor necrosis factor-alpha-stimulated gene 6 in cumulus cells of the cyclooxygenase-2 and EP2 null mice. Endocrinology 144:1008–1019
Odum L, Jessen TE, Andersen CY (2001) Glycosaminoglycan-bound and free inter-alpha-trypsin inhibitor components of follicular fluid. Zygote 9:283–288
Oksjoki S, Sallinen S, Vuorio E, Anttila L (1999) Cyclic expression of mRNA transcripts for connective tissue components in the mouse ovary. Mol Hum Reprod 5:803–808
Paulsson M (1992) Basement membrane proteins: structure, assembly, and cellular interactions. Crit Rev Biochem Mol Biol 27:93–127
Pienimaki JP, Rilla K, Fulop C, Sironen RK, Karvinen S, Pasonen S, Lammi MJ, Tammi R, Hascall VC, Tammi MI (2001) Epidermal growth factor activates hyaluronan synthase 2 in epidermal keratinocytes and increases pericellular and intracellular hyaluronan. J Biol Chem 276:20428–20435
Princivalle M, Hasan S, Hosseini G, de Agostini AI (2001) Anticoagulant heparan sulfate proteoglycans expression in the rat ovary peaks in preovulatory granulosa cells. Glycobiology 11:183–194
Reed CC, Waterhouse A, Kirby S, Kay P, Owens RT, McQuillan DJ, Iozzo RV (2005) Decorin prevents metastatic spreading of breast cancer. Oncogene 24:1104–1110
Reist NE, Magill C, McMahan UJ (1987) Agrin-like molecules at synaptic sites in normal, denervated, and damaged skeletal muscles. J Cell Biol 105:2457–2469
Robker RL, Russell DL, Espey LL, Lydon JP, O'Malley BW, Richards JS (2000) Progesterone-regulated genes in the ovulation process: ADAMTS-1 and cathepsin L proteases. Proc Natl Acad Sci U S A 97:4689–4694
Rodgers RJ, Irving-Rodgers HF (2002) Extracellular matrix of the bovine ovarian membrana granulosa. Mol Cell Endocrinol 191:57–64
Rodgers RJ, Lavranos TC, van Wezel IL, Irving-Rodgers HF (1999) Development of the ovarian follicular epithelium. Mol Cell Endocrinol 151:171–179
Rodgers RJ, Irving-Rodgers HF, van Wezel IL (2000) Extracellular matrix in ovarian follicles. Mol Cell Endocrinol 163:73–79
Rodgers RJ, Irving-Rodgers HF, van Wezel IL, Krupa M, Lavranos TC (2001) Dynamics of the membrana granulosa during expansion of the ovarian follicular antrum. Mol Cell Endocrinol 171:41–48
Rodgers RJ, Irving-Rodgers HF, Russell DL (2003) Extracellular matrix of the developing ovarian follicle. Reproduction 126:415–424
Ruegg MA, Bixby JL (1998) Agrin orchestrates synaptic differentiation at the vertebrate neuromuscular junction. Trends Neurosci 21:22–27
Russell DL, Ochsner SA, Hsieh M, Mulders S, Richards JS (2003) Hormone-regulated expression and localization of versican in the rodent ovary. Endocrinology 144:1020–1031
Sado Y, Kagawa M, Naito I, Ueki Y, Seki T, Momota R, Oohashi T, Ninomiya Y (1998) Organization and expression of basement membrane collagen IV genes and their roles in human disorders. J Biochem (Tokyo) 123:767–776
Salier JP, Rouet P, Raguenez G, Daveau M (1996) The inter-alpha-inhibitor family: from structure to regulation. Biochem J 315:1–9
Salustri A, Yanagishita M, Hascall VC (1989) Synthesis and accumulation of hyaluronic acid and proteoglycans in the mouse cumulus cell-oocyte complex during follicle-stimulating hormone-induced mucification. J Biol Chem 264:13840–13847
Salustri A, Yanagishita M, Underhill CB, Laurent TC, Hascall VC (1992) Localization and synthesis of hyaluronic acid in the cumulus cells and mural granulosa cells of the preovulatory follicle. Dev Biol 151:541–551
Salustri A, Garlanda C, Hirsch E, De Acetis M, Maccagno A, Bottazzi B, Doni A, Bastone A, Mantovani G, Beck Peccoz P, Salvatori G, Mahoney DJ, Day AJ, Siracusa G, Romani L, Mantovani A (2004) PTX3 plays a key role in the organization of the cumulus oophorus extracellular matrix and in in vivo fertilization. Development 131:1577–1586 (Erratum in Development 131:2235)
Schonherr E, Sunderkotter C, Schaefer L, Thanos S, Grassel S, Oldberg A, Iozzo RV, Young MF, Kresse H (2004) Decorin deficiency leads to impaired angiogenesis in injured mouse cornea. J Vasc Res 41:499–508
Shimada H, Kasakura S, Shiotani M, Nakamura K, Ikeuchi M, Hoshino T, Komatsu T, Ihara Y, Sohma M, Maeda Y, Matsuura R, Nakamura S, Hine C, Ohkura N, Kato H (2001) Hypocoagulable state of human preovulatory ovarian follicular fluid: role of sulfated proteoglycan and tissue factor pathway inhibitor in the fluid. Biol Reprod 64:1739–1745
Shindo T, Kurihara H, Kuno K, Yokoyama H, Wada T, Kurihara Y, Imai T, Wang Y, Ogata M, Nishimatsu H, Moriyama N, Oh-hashi Y, Morita H, Ishikawa T, Nagai R, Yazaki Y, Matsushima K (2000) ADAMTS-1: a metalloproteinase-disintegrin essential for normal growth, fertility, and organ morphology and function. J Clin Invest 105:1345–1352
Sirois J, Dore M (1997) The late induction of prostaglandin G/H synthase-2 in equine preovulatory follicles supports its role as a determinant of the ovulatory process. Endocrinology 138:4427–4434
Smith WL, Meade EA, DeWitt DL (1994) Interactions of PGH synthase isozymes-1 and -2 with NSAIDs. Ann N Y Acad Sci 744:50–57
Smith GW, Gentry PC, Long DK, Smith MF, Roberts RM (1996) Differential gene expression within the ovine corpus luteum: identification of secreted protein acidic and rich in cysteine as a major secretory product of small but not large luteal cells. Endocrinology 137:755–762
Suzuki M, Kobayashi H, Tanaka Y, Kanayama N, Terao T (2004) Reproductive failure in mice lacking inter-alpha-trypsin inhibitor (ITI)-ITI target genes in mouse ovary identified by microarray analysis. J Endocrinol 183:29–38
Tasheva ES, Ke A, Conrad GW (2004) Analysis of the expression of chondroadherin in mouse ocular and non-ocular tissues. Mol Vis 10:544–554
Timpl R, Brown JC (1996) Supramolecular assembly of basement membranes. Bioessays 18:123–132
Varani S, Elvin JA, Yan C, DeMayo J, DeMayo FJ, Horton HF, Byrne MC, Matzuk MM (2002) Knockout of pentraxin 3, a downstream target of growth differentiation factor-9, causes female subfertility. Mol Endocrinol 16:1154–1167
Veugelers M, De Cat B, Ceulemans H, Bruystens AM, Coomans C, Durr J, Vermeesch J, Marynen P, David G (1999) Glypican-6, a new member of the glypican family of cell surface heparan sulfate proteoglycans. J Biol Chem 274:26968–26977
Weber M (1992) Basement membrane proteins. Kidney Int 41:620–628
Whitelock JM, Murdoch AD, Iozzo RV, Underwood PA (1996) The degradation of human endothelial cell-derived perlecan and release of bound basic fibroblast growth factor by stromelysin, collagenase, plasmin, and heparanases. J Biol Chem 271:10079–10086
Wisniewski HG, Snitkin ES, Mindrescu C, Sweet MH, Vilcek J (2005) TSG-6 protein binding to glycosaminoglycans: formation of stable complexes with hyaluronan and binding to chondroitin sulfates. J Biol Chem 280:14476–14484
Yiu GK, Chan WY, Ng SW, Chan PS, Cheung KK, Berkowitz RS, Mok SC (2001) SPARC (secreted protein acidic and rich in cysteine) induces apoptosis in ovarian cancer cells. Am J Pathol 159:609–622
Yurchenco PD, Schittny JC (1990) Molecular architecture of basement membranes. FASEB J 4:1577–1590
Zhuo L, Yoneda M, Zhao M, Yingsung W, Yoshida N, Kitagawa Y, Kawamura K, Suzuki T, Kimata K (2001) Defect in SHAP-hyaluronan complex causes severe female infertility. A study by inactivation of the bikunin gene in mice. J Biol Chem 276:7693–7696
Zhuo L, Hascall VC, Kimata K (2004) Inter-alpha-trypsin inhibitor, a covalent protein-glycosaminoglycan-protein complex. J Biol Chem 279:38079–38082
Acknowledgements
The following website http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM was used to seek evidence for roles of ECM in follicular diseases.
Author information
Authors and Affiliations
Corresponding author
Additional information
Research in the authors' laboratories has been supported by the National Health and Medical Research Council of Australia, The University of Adelaide, Wellcome Foundation, and the Clive and Vera Ramaciotti Foundation.
Rights and permissions
About this article
Cite this article
Irving-Rodgers, H.F., Rodgers, R.J. Extracellular matrix in ovarian follicular development and disease. Cell Tissue Res 322, 89–98 (2005). https://doi.org/10.1007/s00441-005-0042-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00441-005-0042-y