title: Oocyte glycoproteins regulate the form and function of the follicle basal lamina and theca cells.
abstract: Maintaining follicle integrity during development, whereby each follicle is a functional unit containing a single oocyte, is essential for the generation of healthy oocytes. However, the mechanisms that regulate this critical function have not been determined. In this paper we investigate the role of the oocyte in maintaining follicle development. To investigate this role, we use a mouse model with oocyte-specific deletion of C1galt1 which is required for the generation of core 1-derived O-glycans. The loss of oocyte-generated O-glycans results in the joining of follicles and the generation of Multiple-Oocyte Follicles (MOFs). The aim was to determine how Mutant follicle development is modified thus enabling follicles to join. Extracellular matrix and follicle permeability were studied using histology, immunohistochemistry and electron microscopy (EM). In ovaries containing Mutant Oocytes, the Follicle basal lamina (FBL) is altered both functionally and structurally from the primary stage onwards with Mutant follicles possessing unexpectedly thicker FBL. In Mutant ovaries, the theca cell layer is also modified with intermingling of theca between adjacent follicles. MOF function was analysed but despite increased numbers of preantral MOFs in Mutants, these do not reach the preovulatory stage after gonadotrophin stimulation. We propose a model describing how oocyte initiated changes in FBL and theca cells result in follicles joining. These data reveal new and important roles for the oocyte in follicle development and follicle integrity.
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women׳s Centre, Level 3, John Radcliffe Hospital, Oxford OX3 9DU, UK.
authors.forename: Alice P
authors.initials: AP
authors.lastname: Christensen
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women׳s Centre, Level 3, John Radcliffe Hospital, Oxford OX3 9DU, UK.
authors.forename: Saloni H
authors.initials: SH
authors.lastname: Patel
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women׳s Centre, Level 3, John Radcliffe Hospital, Oxford OX3 9DU, UK.
authors.forename: Patricia
authors.initials: P
authors.lastname: Grasa
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
authors.forename: Helen C
authors.initials: HC
authors.lastname: Christian
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women׳s Centre, Level 3, John Radcliffe Hospital, Oxford OX3 9DU, UK. Electronic address: suzannah.williams@obs-gyn.ox.ac.uk.
authors.forename: Suzannah A
authors.initials: SA
authors.lastname: Williams
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000166:cytology / Q000196:embryology*; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005700:Galactosyltransferases / Q000235:genetics*; D006023:Glycoproteins / Q000378:metabolism; D006062:Gonadotropins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009865:Oocytes / Q000378:metabolism*; D006080:Ovarian Follicle / Q000166:cytology / Q000196:embryology*; D010539:Permeability; D011134:Polysaccharides / Q000235:genetics; D013799:Theca Cells / Q000166:cytology*
chemical_list: D006023:Glycoproteins; D006062:Gonadotropins; D011134:Polysaccharides; D003094:Collagen; C515597:C1galt1 protein, mouse; D005700:Galactosyltransferases
keywords: Basal lamina; C1galt1; Collagen; Core 1 O-glycans; Electron microscopy; Extracellular matrix; Floxed; Follicle; Laminin; LoxP; Multiple-oocyte follicle; Oocyte; Ovary; T-synthase; ZP3 Cre recombinase