Partial male-to-female reprogramming of mouse fetal testis by Sertoli cell ablation

Abstract

Temporal transcription profiles of fetal testes with Sertoli cell ablation were examined in 4-day culture using a diphtheria toxin (DT)-dependent cell knockout system in AMH-TRECK transgenic (Tg) mice. RNA analysis revealed that ovarian-specific genes, including Foxl2, were ectopically expressed in DT-treated Tg testis explants initiated at embryonic days 12.5–13.5. FOXL2-positive cells were ectopically observed in two testicular regions—near the testicular surface epithelia and around its adjacent mesonephros. The surface FOXL2-positive cells, together with ectopic expression of Lgr5 and Gng13 (markers of ovarian cords), were derived from the testis epithelia/subepithelia, whereas another FOXL2-positive population was the 3βHSD-negative stroma near the mesonephros. In addition to high expression of Fgfr1/Fgfr2 and heparan sulfate proteoglycan (a reservoir for FGF ligand) in these two sites, exogenous FGF9 additives repressed DT-dependent Foxl2 upregulation in Tg testes. These findings imply retention of Foxl2 inducibility in the surface epithelia and peri-mesonephric stroma of the testicular parenchyma, in which certain paracrine signals, including FGF9 derived from fetal Sertoli cells, repress feminization in these two sites of the early fetal testis.

Single-cell transcriptome unravels spermatogonial stem cells and dynamic heterogeneity of spermatogenesis in seasonal breeding teleost

“…In this study, we found that the specific marker genes for Sertoli cells ( gsdf and fgf2 ) and Leydig cells ( igf2 and bmp4 ) were significantly expressed in a cell cluster from the juvenile testes, suggesting that the Sertoli cells and Leydig cells may be differentiated from the same cell precursor. Although the origin of Sertoli and Leydig cells in fish is not fully understood, the fetal Sertoli cells were well known to induce appearance of Leydig cells in mammals (Imaimatsu et al, 2023; Yao and Rodriguez, 2023). Our findings offer valuable insights for further research into the origin of gonadal somatic cells in fish.…”