Abstract
The new concept of mammalian sex maintenance establishes that particular key genes must remain active in the differentiated gonads to avoid genetic sex reprogramming, as described in adult ovaries after Foxl2 ablation. Dmrt1 plays a similar role in postnatal testes, but the mechanism of adult testis maintenance remains mostly unknown. Sox9 and Sox8 are required for postnatal male fertility, but their role in the adult testis has not been investigated. Here we show that after ablation of Sox9 in Sertoli cells of adult, fertile Sox8(-/-) mice, testis-to-ovary genetic reprogramming occurs and Sertoli cells transdifferentiate into granulosa-like cells. The process of testis regression culminates in complete degeneration of the seminiferous tubules, which become acellular, empty spaces among the extant Leydig cells. DMRT1 protein only remains in non-mutant cells, showing that SOX9/8 maintain Dmrt1 expression in the adult testis. Also, Sox9/8 warrant testis integrity by controlling the expression of structural proteins and protecting Sertoli cells from early apoptosis. Concluding, this study shows that, in addition to its crucial role in testis development, Sox9, together with Sox8 and coordinately with Dmrt1, also controls adult testis maintenance.
Highlights
Sox genes encode an important group of transcription factors with relevant roles in many aspects of pre- and post-natal development of vertebrates and other animal taxa
Sox8/9 double homozygous Sox9/8 knockout (DKO) mice fed with a TX-supplemented diet for a maximun of 30 days starting at postnatal day 60 (P60) (Figure 1A) showed EYFP expression in a reduced number of Sertoli cells already 10 days after the beginning of TX administration (10 datx, P70) in the two CreERT2 lines
The number of SOX9+ cells per seminiferous tubule cross section decreased to 15.39 ± 3.36 (37% reduction) in the testes of the Wt1-CreERT2; Sox9f/f; Sox8-/- [Sox9/8 DKO (Wt1)] mice and to 7.49 ± 3.61 (69% reduction) in those of the Sox9-CreERT2; Sox9f/f; Sox8-/- [Sox9/8 DKO (Sox9)] mice, when compared to controls (24.31 ± 2.94) (Figure 1Bd, Figure 1—source data 1)
Summary
Sox genes encode an important group of transcription factors with relevant roles in many aspects of pre- and post-natal development of vertebrates and other animal taxa. There are 20 Sox genes in vertebrates, which are classified into 9 groups. Sox, and Sox (SoxE group) are involved in many developmental processes (reviewed in Lefebvre et al, 2007). All three SoxE genes are expressed during testis development, Sox being essential for testis determination and Sox9/Sox necessary for subsequent embryonic differentiation (Chaboissier, 2004, Barrionuevo et al, 2006, Barrionuevo et al, 2009). Sox can substitute for Sox during testis determination (Polanco et al, 2010). The Y-linked, mammalian sex-determining factor, SRY, upregulates SOX9 which triggers testis differentiation, whereas in the female, the WNT/b -catenin
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
