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Publication : The conditional deletion of steroidogenic factor 1 (Nr5a1) in Sox9-Cre mice compromises testis differentiation.

First Author  Ikeda Y Year  2021
Journal  Sci Rep Volume  11
Issue  1 Pages  4486
PubMed ID  33627800 Mgi Jnum  J:303384
Mgi Id  MGI:6512135 Doi  10.1038/s41598-021-84095-y
Citation  Ikeda Y, et al. (2021) The conditional deletion of steroidogenic factor 1 (Nr5a1) in Sox9-Cre mice compromises testis differentiation. Sci Rep 11(1):4486
abstractText  Steroidogenic factor 1 (NR5A1) is essential for gonadal development. To study the importance of NR5A1 during early gonadal sex differentiation, we generated Sox9-Cre-Nr5a1 conditional knockout (cKO) mice: Sox9-Cre;Nr5a1(flox/flox) and Sox9-Cre;Nr5a1(flox/-) mice. Double-immunostaining for NR5A1 and AMH revealed silenced NR5A1 in Sertoli cells and reduced AMH(+) cells in the gonads of XY Sox9-Cre-Nr5a1 cKO mice between embryonic days 12.5 (E12.5) and E14.5. Double-immunostaining for SOX9 and FOXL2 further indicated an early block in Sertoli cells and ectopic granulosa cell differentiation. The number of cells expressing the Leydig cell marker 3betaHSD obviously reduced in the gonads of XY Sox9-Cre;Nr5a1(flox/-) but not Sox9-Cre;Nr5a1(flox/flox) mice at E15.5. The presence of STRA8(+) cells indicated that germ cells entered meiosis in the gonads of XY Sox9-Cre-Nr5a1 cKO mice. The results of qRT-PCR revealed remarkably reduced and elevated levels of testis and ovary markers, respectively, in the gonads of XY Sox9-Cre-Nr5a1 cKO mice at E12.5E13.5. These data suggested that the loss of Nr5a1 abrogates the testicular pathway and induces the ectopic ovarian pathway, resulting in postnatal partial/complete male-to-female gonadal sex reversal. Our findings provide evidence for the critical role of NR5A1 in murine gonadal sex determination in vivo.
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