title: Molecular analysis of the cumulus matrix: insights from mice with O-glycan-deficient oocytes.
abstract: During follicle development, oocytes secrete factors that influence the development of granulosa and cumulus cells (CCs). In response to oocyte and somatic cell signals, CCs produce extracellular matrix (ECM) molecules resulting in cumulus expansion, which is essential for ovulation, fertilisation, and is predictive of oocyte quality. The cumulus ECM is largely made up of hyaluronan (HA), TNF-stimulated gene-6 (TSG-6, also known as TNFAIP6), pentraxin-3 (PTX3), and the heavy chains (HCs) of serum-derived inter-α-inhibitor proteins. In contrast to other in vivo models where modified expansion impairs fertility, the cumulus mass of C1galt1 Mutants, which have oocyte-specific deletion of core 1-derived O-glycans, is modified without impairing fertility. In this report, we used C1galt1 Mutant (C1galt1(FF):ZP3Cre) and Control (C1galt1(FF)) mice to investigate how cumulus expansion is affected by oocyte-specific deletion of core 1-derived O-glycans without adversely affecting oocyte quality. Mutant cumulus-oocyte complexes (COCs) are smaller than Controls, with fewer CCs. Interestingly, the CCs in Mutant mice are functionally normal as each cell produced normal levels of the ECM molecules HA, TSG-6, and PTX3. However, HC levels were elevated in Mutant COCs. These data reveal that oocyte glycoproteins carrying core 1-derived O-glycans have a regulatory role in COC development. In addition, our study of Controls indicates that a functional COC can form provided all essential components are present above a minimum threshold level, and thus some variation in ECM composition does not adversely affect oocyte development, ovulation or fertilisation. These data have important implications for IVF and the use of cumulus expansion as a criterion for oocyte assessment.
authors: Nuffield Department of Obstetrics and GynaecologyWomen's Centre, Level 3, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UKFaculty of Life SciencesUniversity of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UKWellcome Trust Centre for Cell-Matrix ResearchFaculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
authors: Panayiota
authors: P
authors: Ploutarchou
authors: Nuffield Department of Obstetrics and GynaecologyWomen's Centre, Level 3, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UKFaculty of Life SciencesUniversity of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UKWellcome Trust Centre for Cell-Matrix ResearchFaculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
authors: Pedro
authors: P
authors: Melo
authors: Nuffield Department of Obstetrics and GynaecologyWomen's Centre, Level 3, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UKFaculty of Life SciencesUniversity of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UKWellcome Trust Centre for Cell-Matrix ResearchFaculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK Nuffield Department of Obstetrics and GynaecologyWomen's Centre, Level 3, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UKFaculty of Life SciencesUniversity of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UKWellcome Trust Centre for Cell-Matrix ResearchFaculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
authors: Anthony J
authors: AJ
authors: Day
authors: Nuffield Department of Obstetrics and GynaecologyWomen's Centre, Level 3, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UKFaculty of Life SciencesUniversity of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UKWellcome Trust Centre for Cell-Matrix ResearchFaculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK.
authors: Caroline M
authors: CM
authors: Milner
authors: Nuffield Department of Obstetrics and GynaecologyWomen's Centre, Level 3, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DU, UKFaculty of Life SciencesUniversity of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UKWellcome Trust Centre for Cell-Matrix ResearchFaculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, UK suzannah.williams@obs-gyn.ox.ac.uk.
authors: Suzannah A
authors: SA
authors: Williams
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D054885:Cumulus Cells / Q000166:cytology / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D005306:Fertilization; D005700:Galactosyltransferases / Q000502:physiology*; D007124:Immunoenzyme Techniques; D051379:Mice; D018345:Mice, Knockout; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D006080:Ovarian Follicle / Q000166:cytology / Q000378:metabolism*; D010060:Ovulation / Q000502:physiology; D011134:Polysaccharides / Q000172:deficiency*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D011134:Polysaccharides; D012333:RNA, Messenger; C515597:C1galt1 protein, mouse; D005700:Galactosyltransferases