• PMID: 23935527
• Gene Name: WT1
• Condition: Non-obstructive azoospermia(NOA)
• Association: The findings suggest that Wt1 is important in spermatogenesis by regulating the polarity of SCs via Wnt signaling pathway and that WT1 mutation is one of the genetic causes of NOA in humans.
• Population size: 529
• Population details: 529 human patients with non-obstructive azoospermia(NOA), indicating a strong association between WT1 mutation and NOA
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Non-obstructive azoospermia(NOA)

The Wilms tumor gene, Wt1, is critical for mouse spermatogenesis via regulation of sertoli cell polarity and is associated with non-obstructive azoospermia in humans

Wang XN, Li ZS, Ren Y, Jiang T, Wang YQ, Chen M, Zhang J, Hao JX, Wang YB, Sha RN, Huang Y, Liu X, Hu JC, Sun GQ, Li HG, Xiong CL, Xie J, Jiang ZM, Cai ZM, Wang J, Wang J, Huff V, Gui YT, Gao F.

Azoospermia is one of the major reproductive disorders which cause male infertility in humans; however, the etiology of this disease is largely unknown. In the present study, six missense mutations of WT1 gene were detected in 529 human patients with non-obstructive azoospermia (NOA), indicating a strong association between WT1 mutation and NOA. The Wilms tumor gene, Wt1, is specifically expressed in Sertoli cells (SCs) which support spermatogenesis. To examine the functions of this gene in spermatogenesis, Wt1 was deleted in adult testis using Wt1(flox) and Cre-ER(TM) mice strains. We found that inactivation of Wt1 resulted in massive germ cell death and only SCs were present in most of the seminiferous tubules which was very similar to NOA in humans. In investigating the potential mechanism for this, histological studies revealed that the blood-testis barrier (BTB) was disrupted in Wt1 deficient testes. In vitro studies demonstrated that Wt1 was essential for cell polarity maintenance in SCs. Further studies found that the expression of cell polarity associated genes (Par6b and E-cadherin) and Wnt signaling genes (Wnt4, Wnt11) were downregulated in Wt1 deficient SCs, and that the expression of Par6b and E-cadherin was regulated by Wnt4. Our findings suggest that Wt1 is important in spermatogenesis by regulating the polarity of SCs via Wnt signaling pathway and that WT1 mutation is one of the genetic causes of NOA in humans. FAU - Wang, Xiao Na AU - Wang XN AD - State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China. FAU - Li, Ze Song AU - Li ZS FAU - Ren, Yu AU - Ren Y FAU - Jiang, Tao AU - Jiang T FAU - Wang, Ya Qing AU - Wang YQ FAU - Chen, Min AU - Chen M FAU - Zhang, Jun AU - Zhang J FAU - Hao, Jian Xiu AU - Hao JX FAU - Wang, Yan Bo AU - Wang YB FAU - Sha, Ri Na AU - Sha RN FAU - Huang, Yi AU - Huang Y FAU - Liu, Xiao AU - Liu X FAU - Hu, Jing Chu AU - Hu JC FAU - Sun, Guang Qing AU - Sun GQ FAU - Li, Hong Gang AU - Li HG FAU - Xiong, Cheng Liang AU - Xiong CL FAU - Xie, Jun AU - Xie J FAU - Jiang, Zhi Mao AU - Jiang ZM FAU - Cai, Zhi Ming AU - Cai ZM FAU - Wang, Jun AU - Wang J FAU - Wang, Jian AU - Wang J FAU - Huff, Vicki AU - Huff V FAU - Gui, Yao Ting AU - Gui YT