| First Author | Grasa P | Year | 2015 |
| Journal | FASEB J | Volume | 29 |
| Issue | 2 | Pages | 525-39 |
| PubMed ID | 25416550 | Mgi Jnum | J:218520 |
| Mgi Id | MGI:5617874 | Doi | 10.1096/fj.14-253757 |
| Citation | Grasa P, et al. (2015) Oocytes lacking O-glycans alter follicle development and increase fertility by increasing follicle FSH sensitivity, decreasing apoptosis, and modifying GDF9:BMP15 expression. FASEB J 29(2):525-39 |
| abstractText | 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 approximately 40-50% more eggs than Controls. Here we analyze the basis of this phenotype using Mutant [core 1 beta1,3-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.-Grasa, P., Ploutarchou, P., Williams, S. A. Oocytes lacking O-glycans alter follicle development and increase fertility by increasing follicle FSH sensitivity, decreasing apoptosis, and modifying GDF9:BMP15 expression. |
