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Sox9 and Sox8 protect the adult testis from male-to-female genetic reprogramming and complete degeneration

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Item Type:Article
Title:Sox9 and Sox8 protect the adult testis from male-to-female genetic reprogramming and complete degeneration
Creators Name:Barrionuevo, F.J. and Hurtado, A. and Kim, G.J. and Real, F.M. and Bakkali, M. and Kopp, J.L. and Sander, M. and Scherer, G. and Burgos, M. and Jiménez, R.
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.
Keywords:Sox8, Sox9, Developmental Biology, Male-to-Female Genetic Reprogramming, Stem Cells, Testis Degeneration, Animals, Mice
Publisher:eLife Sciences Publications
Page Range:e15635
Date:21 June 2016
Official Publication:https://doi.org/10.7554/eLife.15635
PubMed:View item in PubMed

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