• PMID: 29531833
• Gene Name: ZCCHC13
• Condition: Non-obstructive azoospermia
• Association: Associated
• Population size: 4
• Population details: 4 with Non Obstructive Azoospermia
• Sex: Male
• Infertility type: Male infertility
• Associated genes: NGS

Novel biomarker ZCCHC13 revealed by integrating DNA methylation and mRNA expression data in non-obstructive azoospermia

Li Z, Chen S, Yang Y, Zhuang X, Tzeng CM.

The objective of this study was to identify genes regulated by methylation that were involved in spermatogenesis failure in non-obstructive azoospermia (NOA). Testis biopsies of patients with NOA and OA (with normal spermatogenesis) were evaluated by microarray analysis to examine DNA methylation and mRNA expression using our established integrative approach. Of the coordinately hypermethylated and down-regulated gene list, zinc-finger CCHC-type containing 13 (ZCCHC13) was present within the nuclei of germ cells of testicular tissues according immunohistochemistry, and there was decreased protein expression in men with NOA compared with OA controls. Mechanistic analyses indicated that ZCCHC13 increased c-MYC expression through the p-AKT and p-ERK pathways. To confirm the changes in ZCCHC13 expression in response to methylation, 5-aza-2'-deoxycitidine (5-Aza), a hypomethylating agent, was administered to mouse spermatogonia GC-1 cells. We demonstrated that 5-Aza enhanced protein and mRNA expression of ZCCHC13 epigenetically, which was accompanied by activation of p-AKT and p-ERK signaling. Our data, for the first time, demonstrate that ZCCHC13 is an important signaling molecule that positively regulates the AKT/MAPK/c-MYC pathway and that methylation aberrations of ZCCHC13 may cause defects in testis development in human disease, such as NOA. FAU - Li, Zhiming AU - Li Z AD - 1Translational Medicine Research Center-Key Laboratory for Cancer T-Cell Theranostics and Clinical Translation, School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian China. ISNI: 0000 0001 2264 7233. GRID: grid.12955.3a AD - 2Department of Urology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian China. GRID: grid.412625.6 FAU - Chen, Shuai AU - Chen S AD - 1Translational Medicine Research Center-Key Laboratory for Cancer T-Cell Theranostics and Clinical Translation, School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian China. ISNI: 0000 0001 2264 7233. GRID: grid.12955.3a FAU - Yang, Yufeng AU - Yang Y AD - 2Department of Urology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian China. GRID: grid.412625.6 FAU - Zhuang, Xuan AU - Zhuang X AD - 2Department of Urology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian China. GRID: grid.412625.6 AD - 3Department of Urology, The First Clinical Medical College of Fujian Medical University, Fuzhou, Fujian China. ISNI: 0000 0004 1797 9307. GRID: grid.256112.3