No Female Germline Stem Cells Were Identified by Advanced Dual Recombinase-Based Lineage Tracing System

Whether female germline stem cells (fGSCs) exist in postnatal mammalian ovaries has been debated for decades. Since the fGSCs were first reported in 2004, a large number of studies have been conducted using different approaches. However, the persistent controversy surrounding the results has caused confusion among many researchers and clinicians. To clearly clarify this question, we developed advanced tracing system to label any possible fGSCs in adult female mice. Our results showed that no Stra8-expressing germ cells were detected in the ovaries of adult female mice using a long-term uninterrupted lineage tracing system under both physiological and pathological conditions. Furthermore, we adopted the interleaved reporter tracing system that allows mutually exclusive labelling of germ cells and non-germ cell populations while preventing potential secondary recombination. This approach revealed no evidence of de novo germ cell formation during postnatal life. Together, our findings provide the evidence that fGSCs and postnatal oogenesis do not exist under both physiological and pathological conditions in mouse models, therefore reinforcing the notion that the primordial follicle pool established perinatally serves as the primary source of oocytes through the entire reproductive lifespan.