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: Patricia Grasa, Panayiota Ploutarchou, Suzannah A Williams
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 29 Issue 2 Pg. 525-39 (Feb 2015) ISSN: 1530-6860 [Electronic] United States
• PMID: 25416550 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © FASEB.

Chemical References

• Bax protein, mouse
• Bmp15 protein, mouse
• Bone Morphogenetic Protein 15
• Gdf9 protein, mouse
• Growth Differentiation Factor 9
• Polysaccharides
• Proto-Oncogene Proteins c-bcl-2
• bcl-2-Associated X Protein
• Bcl2 protein, mouse
• Follicle Stimulating Hormone

Topics

• Alleles
• Animals
• Apoptosis
• Bone Morphogenetic Protein 15 (metabolism)
• Estrous Cycle
• Female
• Fertility
• Follicle Stimulating Hormone (metabolism)
• Gene Expression Regulation
• Genotype
• Growth Differentiation Factor 9 (metabolism)
• Mice
• Mutation
• Oocytes (cytology)
• Ovarian Follicle (metabolism)
• Ovary (metabolism)
• Phenotype
• Polysaccharides (chemistry)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• bcl-2-Associated X Protein (metabolism)