RT Journal Article
T1 Sox9 and Sox8 protect the adult testis from male-to-female genetic reprogramming and complete degeneration
A1 Barrionuevo, Francisco J.
A1 Hurtado, Alicia
A1 Kim, Gwang-Jin
A1 Real, Francisca M.
A1 Bakkali, Mohammed
A1 Kopp, Janel L.
A1 Sander, Maike
A1 Scherer, Gerd
A1 Burgos, Miguel
A1 Jimenez, Rafael
K1 Autosomal sex reversal
K1 Sry-related gene
K1 Campomelic dysplasia
K1 Mammalian testis
K1 Sertoli-cells
K1 Transcription factors
K1 Male-fertility
K1 Beta-catenin
K1 Iberian mole
K1 Expression
AB 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.
PB Elife sciences publications ltd
SN 2050-084X
YR 2016
FD 2016-06-07
LK http://hdl.handle.net/10668/19394
UL http://hdl.handle.net/10668/19394
LA en
NO Barrionuevo FJ, Hurtado A, Kim GJ, Real FM, Bakkali M, Kopp JL, et al. Sox9 and Sox8 protect the adult testis from male-to-female genetic reprogramming and complete degeneration. Elife. 2016 Jun 21;5:e15635.
DS RISalud
RD Apr 7, 2025