Sex-specific expression and function of TRIM28 during mouse primordial germ differentiation

Area of Science:

• Developmental Biology
• Genetics
• Reproductive Biology

Background:

• Mammalian primordial germ cells (PGCs) are crucial for transmitting genetic material across generations.
• Transposable elements (TEs) pose a significant risk to genomic stability during embryonic development.
• Tight regulation of TEs is essential for maintaining germline integrity.

Purpose of the Study:

• To investigate the role of tripartite motif-containing 28 (TRIM28) in controlling transposable elements (TEs) during mammalian PGC differentiation.
• To elucidate the sex-specific regulation of TRIM28 and its impact on PGCs.
• To understand how TRIM28-mediated TE repression affects PGC development and fertility.

Main Methods:

• Analysis of TE accessibility during PGC differentiation.
• Investigation of TRIM28 regulation and its targets in both testicular and ovarian PGCs.
• Assessment of PGC differentiation, 2-cell (2C)-associated gene expression, and DAZL activation.

Main Results:

• TRIM28, a master regulator of TEs, is subject to sex-specific regulation and represses sex-specific TEs.
• TRIM28 prevents the upregulation of 2C-associated genes and PGC differentiation defects in both sexes.
• Disruption of TRIM28 function leads to distinct developmental issues: testicular PGCs fail to differentiate, while ovarian PGCs exhibit inefficient meiosis, resulting in a diminished ovarian reserve.

Conclusions:

• TRIM28 plays a critical sex-specific role in safeguarding the mammalian germline against TE-mediated genomic damage.
• Dysregulation of TRIM28 impacts PGC development and function differently in males and females, with significant consequences for fertility.
• Understanding TRIM28's function is vital for comprehending germline development and potential causes of infertility.