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

Author:

Barrionuevo Francisco J12ORCID,Hurtado Alicia12,Kim Gwang-Jin3,Real Francisca M12,Bakkali Mohammed4ORCID,Kopp Janel L5ORCID,Sander Maike5,Scherer Gerd3,Burgos Miguel12ORCID,Jiménez Rafael12ORCID

Affiliation:

1. Departamento de Genética e Instituto de Biotecnología, Universidad de Granada, Granada, Spain

2. Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain

3. Institute of Human Genetics, University of Freiburg, Freiburg, Germany

4. Departamento de Genética, Facultad de Ciencias, Universidad de Granada, Granada, Spain

5. Department of Pediatrics and Cellular and Molecular Medicine, University of California, San Diego, San Diego, United States

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.

Funder

Ministerio de Ciencia e Innovación

National Institute of Diabetes and Digestive and Kidney Diseases

Deutsche Forschungsgemeinschaft

Andalussian Government, Junta de Andalucía

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3