X chromosome-wide identification of SNVs in microRNA genes and non-obstructive azoospermia risk in Han Chinese population.
Human X chromosome has higher densities of microRNAs (miRNAs) compared to the average densities on autosomes. Given that numbers of X-linked miRNAs can escape from meiotic sex chromosome inactivation (MSCI) silencing, it is proposed that X-linked miRNAs may play critical roles in the process of spermatogenesis. To test the hypothesis, we performed DNA capture sequencing of human X-linked miRNAs, which was followed by a two-stage case-control study to identify the non-obstructive azoospermia (NOA) related single nucleotide variants (SNVs) in 1107 NOA cases and 1191 fertile healthy controls. Eventually, we found rs5951785, located near hsa-miRNA-506/507, increased the risk of NOA, while rs1447393, near hsa-miRNA-510, decreased the risk of NOA. Functional analysis revealed that rs5951785 significantly inhibited cell proliferation and induced cell apoptosis. Taken together, our results demonstrated that X-linked miRNAs played important roles in the pathogenesis of NOA.
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
Juan
J
Ji
Epigenetics & Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Yufeng
Y
Qin
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
Ran
R
Zhou
Department of Pediatric Surgery, State Key Laboratory of Reproductive Medicine, Nanjing Children's Hospital Affiliated Nanjing Medical University, Nanjing 210008, China.
Rujin
R
Zang
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
Zhenyao
Z
Huang
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
Yan
Y
Zhang
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
Minjian
M
Chen
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
Wei
W
Wu
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
Ling
L
Song
Department of Children Health Care, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing 210029, China.
Xiufeng
X
Ling
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.|Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Hongbing
H
Shen
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.|Department of Epidemiology and Biostatistics and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Zhibin
Z
Hu
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
Yankai
Y
Xia
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
Chuncheng
C
Lu
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.|Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
Xinru
X
Wang
D017209:Apoptosis; D053713:Azoospermia / Q000208:ethnology / Q000235:genetics*; D016022:Case-Control Studies; D049109:Cell Proliferation; D002681:China; D041321:Chromosomes, Human, X; D015331:Cohort Studies; D020868:Gene Silencing; D050172:Genes, X-Linked; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D017422:Sequence Analysis, DNA; D013091:Spermatogenesis / Q000235:genetics*
D035683:MicroRNAs
X-linked miRNAs; non-obstructive azoospermia