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

Development. 2025 Nov 15;152(22):dev204827. doi: 10.1242/dev.204827. Epub 2025 Nov 24.

Abstract

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.

Keywords: Ilp8; Lgr3; Mature follicle sensor; Oocyte aging; Virgin ovulation.

MeSH terms

  • Aging
  • Animals
  • Cellular Senescence*
  • Drosophila Proteins* / genetics
  • Drosophila Proteins* / metabolism
  • Drosophila melanogaster* / metabolism
  • Female
  • Intercellular Signaling Peptides and Proteins* / genetics
  • Intercellular Signaling Peptides and Proteins* / metabolism
  • Oocytes* / cytology
  • Oocytes* / metabolism
  • Oocytes* / physiology
  • Ovarian Follicle* / cytology
  • Ovarian Follicle* / metabolism
  • Ovary* / metabolism
  • Ovulation / genetics
  • Ovulation / physiology
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism

Substances

  • Drosophila Proteins
  • Receptors, G-Protein-Coupled
  • insulin-like peptide 8, Drosophila
  • Lgr3 protein, Drosophila
  • Intercellular Signaling Peptides and Proteins