Germ Cell Proliferation-Growth Balance in Fish – PROBA

One of the most compelling questions in reproductive biology, both from a fundamental and applied perspective, is how adult fish maintain their exceptionally high long-term fecundity. Female fish can produce from a few dozen to several million eggs per season, according to species. But how is such fecundity sustained throughout successive reproductive cycles?
This question raises a fundamental issue: could germline stem cells play an active role in sustaining egg formation during adulthood? If so, the whole process of egg formation (oogenesis) would remain active throughout the female’s life, including the earliest stages of germ cell proliferation, which give rise to immature oocytes. These immature oocytes then enter a growth phase, ultimately leading to the formation of eggs (i.e., unfertilized oocytes ready for spawning). Although the presence of early germ cells in the adult fish ovary was clearly established nearly twenty years ago, their actual contribution to oocyte renewal in adult remains largely unknown.
Building on preliminary data and modeling of oocyte growth dynamics across the female lifespan, we hypothesize in PROBA (Germ Cell Proliferation–Growth Balance in fish) that germ cell proliferation and oocyte growth both contribute to sustaining long-term female fecundity. We propose that these two processes are tightly coordinated, maintaining a functional balance governed by inverse dynamics: when oocyte growth is active, germ cell proliferation is reduced, and vice versa. This balance is further hypothesized to be modulated by photoperiod; a seasonal environmental cue known to regulate oocyte growth.
The goal of PROBA is to test this hypothesis and to decipher the core cellular mechanisms that regulate germ cells activity in adult female fish. Designed as an interdisciplinary project, PROBA combines state-of-the-art approaches such as 3D imaging, single-cell RNA sequencing, and mathematical modeling, using medaka (Oryzias latipes) as a model organism. The project will explore how photoperiod modulates the germ cell lineage and will integrate experimental data into a mathematical model (including hormonal regulations) to provide a precise analysis of the delicate balance between germ cell proliferation and oocyte growth.
By addressing this question, PROBA will shed new light on adult germline stem cells, a topic still largely unexplored in fish. It will establish a functional link between photoperiod and germ cells activity, and propose a novel conceptual and methodological framework applicable to other biological systems at the intersection of reproductive biology, adult stem cell regulation, and tissue remodeling. PROBA is thus positioned at the forefront of reproductive biology. Beyond reproductive biology, the knowledge generated by PROBA will open new perspectives for aquaculture, where the control of female fecundity represents a major challenge for broodstock management, for both wild and farmed species. The resulting model, with its broad applicability, could be adapted to other species and used to explore the effects of additional environmental factors, such as temperature, a key challenge in aquaculture in the context of climate change.