DMRT1 prevents female reprogramming in the postnatal mammalian testis
View abstract on PubMed
Summary
This summary is machine-generated.Mammalian sex determination is maintained by competing gene networks. Loss of DMRT1 in adult male mice reprograms Sertoli cells into granulosa cells, revealing gonadal sex plasticity.
Area Of Science
- Developmental Biology
- Genetics
- Reproductive Biology
Background
- Mammalian sex determination is controlled by the SRY gene, initiating differentiation of bipotential gonadal precursors into Sertoli (male) or granulosa (female) cells.
- Sex determination involves a balance between male (SRY-SOX9) and female (WNT/β-catenin) regulatory networks.
- The female sex determination pathway is plastic; loss of FOXL2 in adult granulosa cells can lead to reprogramming into Sertoli cells.
Purpose Of The Study
- To investigate the plasticity of sexual fate in adult mammalian testes.
- To determine if loss of the DMRT1 transcription factor in adult Sertoli cells can reprogram testicular cells.
- To explore the conserved mechanisms of gonadal sex determination and their implications for human health.
Main Methods
- Genetic manipulation in adult mice to induce the loss of DMRT1 in Sertoli cells.
- Analysis of gonadal cell fate, gene expression (FOXL2 activation), and tissue morphology.
- Comparative analysis of conserved sex-determining genes across vertebrates and metazoans.
Main Results
- Loss of DMRT1 in adult mouse Sertoli cells triggered reprogramming into granulosa cells.
- Reprogrammed testes exhibited theca cell formation, estrogen production, and feminized germ cells.
- DMRT1 is essential for maintaining male sex determination in adult mammals, highlighting competing regulatory networks.
Conclusions
- Gonadal sex in mammals is surprisingly labile, maintained by antagonistic interactions between DMRT1 and FOXL2.
- These findings suggest that the DMRT1-FOXL2 antagonism may be conserved across vertebrates and metazoans.
- Understanding DMRT1's role in reprogramming may elucidate the etiology of human disorders of sexual differentiation and testicular cancer.