MAEL promoter hypermethylation is associated with de-repression of LINE-1 in human hypospermatogenesis.

摘要: Study question Does the hypermethylation of maelstrom spermatogenic transposon silencer (MAEL) promoter and subsequent de-repression transposable elements represent one causes failure in infertile men? Summary answer Experimental a specific region (-131 to +177) MAEL leads decreased expression with increased element LINE-1 (L1) men methylation is associated severity failure. What known already induces repression male germline required for mammalian meiotic progression post-meiotic spermiogenesis. Patients non-obstructive azoospermia (NOA), defined as no sperm ejaculate due failure, histopathologically proven hypospermatogenesis (HS) not uncommon its etiology largely unknown. design, size, duration Luciferase reporter assay targeted DNA model were used explore effects on gene expression. Germ cell-enriched testicular cells from patients determine levels expressions L1. Participants/materials, setting, methods Twenty-six NOA HS 12 obstructive normal spermatogenesis (NS) enrolled this study. Demographic clinical information obtained. The was determined by scoring system. 26 CpGs measured, quantitative real-time RT-PCR expressional Main results role chance Targeted suppressed de-repressed L1 activity vitro. had significantly higher mean consecutive promoter, compared NS. negatively correlated transcript level severe defect. HS. No differences age, frequency insults genetic anomalies noted between high or low levels. Large scale data N/A. Limitations, reasons caution Because difficulty use human germ study, vitro performed using NCI-H358 activity. isolated sample relatively few, purity cell populations determined. Wider implications findings Measurement may be feasible predict outcome retrieval. funding/competing interests This work supported through grants Ministry Science Technology Taiwan (100-2314-B-006-017) National Cheng Kung University Hospital, Tainan, (NCKUH 20120266). authors declare conflicts interest.