Germ stem cells are active in postnatal mouse ovary under physiological conditions

Area of Science:

• Reproductive Biology
• Developmental Biology
• Stem Cell Research

Background:

• The existence of active ovarian germ stem cells in postnatal mammalian ovaries remains controversial, with conflicting in vitro and in vivo evidence.
• Previous studies suggested germ stem cells in mouse, pig, and human ovaries, but in vivo data challenged their presence in mice.

Purpose of the Study:

• To investigate the presence and function of active ovarian germ stem cells in postnatal mouse ovaries under physiological conditions.
• To resolve the controversy regarding the in vivo existence and activity of ovarian germ stem cells.

Main Methods:

• Utilized a tamoxifen-inducible tracing system in Octamer-binding transcription factor 4 (Oct4)-MerCreMer transgenic mice crossed with R26R-enhanced yellow fluorescent protein (EYFP) mice.
• Labeled Oct4-expressing germ cells and traced their fate for up to 4 months, assessing DNA replication, mitotic division, meiosis entry, and primordial follicle formation.
• Employed immunofluorescent staining, EYFP-labeled single-cell RT-PCR, and 5-bromodeoxyuridine triphosphate incorporation assay to analyze germ cell activity.

Main Results:

• Demonstrated persistent meiosis entry and primordial follicle replenishment by labeled germ cells over 4 months.
• Captured evidence of mitotic DNA replication and division in marked germ cells.
• Identified Oct4(+) deleted in azoospermia-like (Dazl)(-) cells as containing a population of ovarian germ stem cells.

Conclusions:

• Unambiguously supports the presence and function of active germ stem cells in postnatal mouse ovaries.
• These stem cells play a crucial role in replenishing the primordial follicle pool under physiological conditions.
• Further research is needed to identify specific markers and evaluate the significance of these stem cells in normal ovarian function.