Mouse fertility is enhanced by oocyte-specific loss of core 1-derived O-glycans.

Regulation of the number of eggs ovulated by different mammalian species remains poorly understood. Here we show that oocyte-specific deletion at the primary follicle stage of core 1 beta1,3-galactosyltransferase (T-synthase; generates core 1-derived O-glycans), leads to a sustained increase in fertility. T-syn mutant females ovulated 30-50% more eggs and had a sustained increase in litter size compared to controls. Ovarian weights and follicle numbers were greater in mutants, but follicular apoptosis was not decreased. The number of follicles entering the growing pool was unaltered, but 3-wk mutants ovulated fewer eggs, suggesting that increased fertility results from prolonged follicle development. T-syn mutant ovaries also contained numerous multiple-oocyte follicles (MOFs) that appeared to form by adjacent, predominantly preantral, follicles joining--a new mechanism for MOF generation. Ovulation of multiple eggs from MOFs was not the reason for increased fertility based on ovulated egg and corpora lutea numbers. Thus, the absence of T-synthase caused modified follicular development, leading to the maturation and ovulation of more follicles, to MOF formation at late stages of folliculogenesis, and to increased fertility. These results identify novel roles for glycoproteins from the oocyte as suppressors of fertility and regulators of follicular integrity in the mouse.