title: Oocytes lacking O-glycans alter follicle development and increase fertility by increasing follicle FSH sensitivity, decreasing apoptosis, and modifying GDF9:BMP15 expression.
abstract: The number of eggs ovulated varies within and between species and is influenced by many variables. However, the regulatory mechanisms remain poorly understood. We previously demonstrated a key role for the oocyte because mice generating oocytes deficient in core 1-derived O-glycans ovulate ∼40-50% more eggs than Controls. Here we analyze the basis of this phenotype using Mutant [core 1 β1,3-galactosyltransferase 1 (C1galt1)(FF):zona pellucida glycoprotein 3 Cre (ZP3Cre)] and Control (C1galt1(FF)) female mice. In culture, Mutant follicles exhibited delayed antrum formation [indicative of follicle stimulant hormone (FSH) dependence] and increased sensitivity to FSH. Although the Mutant estrous cycle was extended, comprehensive endocrine changes were not observed; rather FSH, LH, inhibin B, and anti-Mullerian hormone were temporally altered, revealing estrous cycle stage-specific modifications to the hypothalamic-pituitary-gonadal axis. At proestrus, when FSH levels were decreased in Mutants, ovaries contained more, smaller, preantral follicles. Mutant follicles exhibited reduced levels of apoptosis, and both B-cell lymphoma 2 (Bcl-2) and BCL-2-associated X protein (Bax) were altered compared with Controls. Mutant ovaries also had an increase in the expression ratio of growth differentiation factor 9 (GDF9):bone morphogenetic protein 15 (BMP15) at diestrus. On the basis of these data, we propose that modified oocyte glycoproteins alter GDF9:BMP15 expression modifying follicle development resulting in the generation of more follicles. Thus, the oocyte is a key regulator of follicle development and has a crucial role in determining ovulation rate.
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Patricia
authors.initials: P
authors.lastname: Grasa
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Panayiota
authors.initials: P
authors.lastname: Ploutarchou
authors.affiliation: Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford, United Kingdom suzannah.williams@obs-gyn.ox.ac.uk.
authors.forename: Suzannah A
authors.initials: SA
authors.lastname: Williams
mesh_terms: D000483:Alleles; D000818:Animals; D017209:Apoptosis; D055430:Bone Morphogenetic Protein 15 / Q000378:metabolism*; D030762:Estrous Cycle; D005260:Female; D005298:Fertility; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D005786:Gene Expression Regulation; D005838:Genotype; D055429:Growth Differentiation Factor 9 / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D009865:Oocytes / Q000166:cytology*; D006080:Ovarian Follicle / Q000378:metabolism; D010053:Ovary / Q000378:metabolism; D010641:Phenotype; D011134:Polysaccharides / Q000737:chemistry*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; C525902:Bmp15 protein, mouse; D055430:Bone Morphogenetic Protein 15; C525898:Gdf9 protein, mouse; D055429:Growth Differentiation Factor 9; D011134:Polysaccharides; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C052617:Bcl2 protein, mouse; D005640:Follicle Stimulating Hormone
keywords: C1galt1; T-syn; endocrine profile; ovary; ovulation rate