An asynchronous production line of meiotic prophase I in the mouse fetal ovary

The initiation of meiosis in the female germline of mammals is a gradual process, but there is currently no clear quantitative framework for determining the precise timing of its onset. Here, we attempt to standardize the description of meiotic entry timing through a systematic, quantitative analysis of meiotic entry and progression in the mouse fetal ovary. Using dynamic expression profiling of key regulators Stra8, Sycp1, and Sycp3 alongside proliferation markers, we demonstrate that germ cells enter meiosis asynchronously and continuously between embryonic days E12.5 and E16.5. During this extended period, mitotic proliferation persists, indicating that germ cells are progressively recruited into the meiotic pathway rather than halting division simultaneously. Homologous chromosome synapsis, marked by Sycp1/Sycp3 co-localization, initiates at E14.5 and is completed prenatally by E18.5. Using stage-composition data, we constructed a continuous-time Markov chain model to infer a population-level meiotic stage clock. This model estimates approximately conserved population-level effective intervals from the modeled early-prophase L compartment to pachytene-stage synapsis (∼72 h) and to the late-prophase/dictyate-associated D-state transition (∼91 h) across modeled cohort-start times. Our findings refine the conventional view by quantitatively defining the extended window of meiotic entry and subsequent progression through prophase I.