Decreased oocyte DAZL expression in mice results in increased litter size by modulating FSH-induced follicular growth Short title-Oocyte DAZL expression affects follicular FSH sensitivity Summary sentence-Decreased oocyte DAZL expression alters the response of follicles to FSH allowing earlier follicular maturation and survival in low plasma FSH concentrations, resulting in increased litter size.

While the germ cell specific RNA binding protein, DAZL, is essential for oocytes to survive meiotic arrest, DAZL heterozygous (het) mice have an increased ovulation rate which is associated with elevated inhibin B and decreased plasma FSH. The relationship between decreased oocyte DAZL expression and enhanced follicular development in het mice was investigated using in vitro follicle cultures and in vivo modulation of endogenous FSH by treating mice with inhibin and exogenous FSH. In vitro, follicles from het mice are more sensitive to FSH than wild-type (wt) and can grow in FSH concentrations which are deleterious to wt follicles. In vivo, despite no differences between genotypes in follicle population profiles, analysis of granulosa cell areas in antral follicles identified a significantly greater number of antral follicles with increased granulosa cell area in het ovaries. Modulation of FSH in vivo using decreasing doses of FSH or ovine follicular fluid (oFF) as a source of inhibin confirmed the increased responsiveness of het antral follicles to FSH. Significantly more follicles expressing aromatase protein confirmed the earlier maturation of granulosa cells in het mice. In conclusion, it is suggested that DAZL represses specific unknown genes which regulate the response of granulosa cells to FSH. If this repression is reduced as in DAZL het mice, then follicles can grow to the late follicular stage despite declining levels of circulating FSH, thus leading to more follicles ovulating and increased litter size.