A Novel Mutation of DAX-1 Associated with Secretory Azoospermia

Lisha Mou; Nie Xie; Lihua Yang; Yuchen Liu; Ruiying Diao; Zhiming Cai; Honggang Li; Yaoting Gui

doi:10.1371/journal.pone.0133997

A Novel Mutation of DAX-1 Associated with Secretory Azoospermia

PLoS One. 2015 Jul 24;10(7):e0133997. doi: 10.1371/journal.pone.0133997. eCollection 2015.

Authors

Lisha Mou¹, Nie Xie¹, Lihua Yang², Yuchen Liu³, Ruiying Diao³, Zhiming Cai³, Honggang Li⁴, Yaoting Gui²

Affiliations

¹ Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Domesticated Organ Medical Engineering Research and Development Center, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, China; Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Biomedical Research Institute, Shenzhen PKU-HKUST Medical Center, Shenzhen, 518036, China.
² Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Biomedical Research Institute, Shenzhen PKU-HKUST Medical Center, Shenzhen, 518036, China.
³ Shenzhen Key Laboratory of Genitourinary Tumor, Shenzhen Domesticated Organ Medical Engineering Research and Development Center, Shenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, China.
⁴ The Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Abstract

Secretory azoospermia is a severe form of male infertility caused by unknown factors. DAX-1 is predominantly expressed in mammalian reproductive tissues and plays an important role in spermatogenesis because Dax-1 knockout male mice show spermatogenesis defects. To examine whether DAX-1 is involved in the pathogenesis of secretory azoospermia in humans, we sequenced all of the exons of DAX-1 in 776 patients diagnosed with secretory azoospermia and 709 proven fertile men. A number of coding mutations unique to the patient group, including two synonymous mutations and six missense mutations, were identified. Of the missense mutations, our functional assay demonstrated that the V385L mutation caused the reduced functioning of DAX-1. This novel mutation (p. V385L) of DAX-1 is the first to be identified in association with secretory azoospermia, thereby highlighting the important role of DAX-1 in spermatogenesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Animals
Azoospermia / genetics*
DAX-1 Orphan Nuclear Receptor / genetics*
Genetic Association Studies
Genetic Predisposition to Disease
Humans
Infertility, Male / genetics*
Male
Middle Aged
Mutation*
Spermatogenesis / genetics*
Young Adult

Substances

DAX-1 Orphan Nuclear Receptor

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (grant number 31271244 to YG, 81200465 to LM) and the Shenzhen Foundation of Science and Technology (grant number GJHZ20140414170821192 to NX, JCYJ20140414170821337 to NX, GJHZ20130412153906740 to NX). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.