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• W2890624193 abstract "To identify differences in the testicular transcriptome of men with non-obstructive azoospermia (NOA) and determine markers to predict the best candidates for a successful surgical sperm retrieval. Over 9 months, surgical samples were collected from NOA men (n=5) undergoing a testicular sperm extraction (TESE). Samples were assessed for differential gene expression by next-generation RNA-sequencing and expression patterns were classified based on a successful (NOA+) (n=2) or failed (NOA-) (n=3) sperm retrieval. Gene expression profiles of these men were compared to a control with acquired obstructive azoospermia (OA). Testicular samples from 5 NOA men were assessed; no Y microdeletions were detected. Samples that did not yield spermatozoa (NOA-) were searched extensively (71 ± 10 minutes) by several embryologists to confirm a failed TESE attempt. About 200uL of tissue from each sample was processed for RNA isolation using a commercially available kit and protocol. RNA isolates were sequenced by Illumina HiSeq at 2x150bp configuration per lane with ∼58M reads per sample. A log fold change of >2 and an FDR of P<0.05 were considered significant. TESE RNA samples yielded a concentration of 41.1 ± 29 ng/μL and an RNA integrity number of 4.6 ± 1. Analysis of differential gene expression grouped by ontology revealed a significant reduction in gene expression related to spermatogenesis in NOA men versus OA. Expression levels of germ cell markers in NOA samples were present yet significantly lower than the control, such as DAZL (P<0.001), indicating a reduced germ cell presence. NOA- patients had 30.8% of spermatogenesis-related genes significantly under-expressed while NOA+ men evidenced a reduction of only 16.7% compared to a control. Interestingly, a subset of genes were significantly under-expressed exclusively in NOA- patients, primarily related to meiosis, and evidenced a reduced expression in 77.8% of genes related to the synaptonemal complex assembly (HORMAD1, SYCE1, SYCE3, SYCP1, SYCP2, and TRIP13; P<0.0001) and regulation of chromosome organization (MEIOB; P<0.00001) and segregation (STAG3; P<0.01). These genes were not significantly under-expressed in NOA+ men. These findings suggest that failure to retrieve spermatozoa was due to a maturation arrest of the germ cells in the extracted tubules. While the etiology of NOA is still unclear, RNA-seq can help gauge the spermatogenetic state and potentially provide the urologist with a noninvasive marker to select best candidates for a successful sperm retrieval, which could be tested on the seminal fluid, sparing the patient a surgical procedure. This information may also be useful for counselling severe male factor patients, pre- and/or post-TESE, and set realistic expectations for reproduction." @default.
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• W2890624193 date "2018-09-01" @default.
• W2890624193 modified "2023-09-25" @default.
• W2890624193 title "Differential expression of testicular function can reveal why some NOA men successfully yield spermatozoa" @default.
• W2890624193 doi "https://doi.org/10.1016/j.fertnstert.2018.07.484" @default.
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