ILP8 serves as a mature follicle sensor to prevent excessive accumulation of mature follicles in Drosophila ovaries and oocyte aging

Excessive mature follicle accumulation in ovaries harms oocyte health and offspring viability. The mechanism by which females count mature follicles in their ovaries remains a mystery. Recent work demonstrated that Drosophila insulin-like peptide 8 (ILP8) is expressed in mature follicle cells but not in younger follicles. Here, we found that ILP8 is not essential for mating-induced ovulation but plays a crucial role in inducing ovulation in virgin females and preventing excessive accumulation of mature follicles. Excessive accumulation of mature follicles in ilp8-knockdown females leads to poor oocyte quality. In addition, knockdown of Lgr3 (Leucine-rich repeat-containing G protein-coupled receptor 3), encoding a previously identified ILP8 receptor, globally or neuronally showed similar ovulation/egg laying defects, accumulation of mature follicles and poor oocyte quality in virgin females. Therefore, ILP8 functions as a mature follicle sensor to prevent excessive accumulation of mature follicles and maintain oocyte quality, likely through the neuronal Lgr3 receptor in virgin females. Our findings suggest that ILP8/Lgr3 is likely essential for maintaining the optimal reproductive fitness of virgin females and for species survival in the wild, where mating success is not guaranteed.