P-712 Transcriptomic Prediction of Spermatogenesis in the Ejaculates of Nonobstructive Azoospermic Men and Genomic Characterization of their Embryo Developmental Competence

Abstract Study question Can the genomic assessment of ejaculates from azoospermic men predict successful sperm extraction at testicular biopsy (TESE) and provide information on their reproductive potential? Summary answer RNAseq NOA identified transcriptomic predictors TESE outcome, while DNAseq evidenced gene-related mechanistics linked to performance. What is known already The most puzzling form azoospermia type. chances surgical retrieval for these cases can be unpredictable, even when a benign histopathology has been obtained. ability identify individuals with complete loss spermatogenesis seminiferous tubule level would help eliminate anesthesia risks, as well financial emotional distress. We propose noninvasively assess retrieval. utilize impact germline mutations embryo developmental competence surgically retrieved gametes. design, size, duration Over 4 years, we recruited normal peripheral karyotypes (n = 23), confirmed by absence spermatozoa in extensive semen analyses. performed epigenetic assessments compare profiles according whether were successfully after ((+)Sperm,n=11), or not ((-)Sperm,n=12). then (IRB 1006101085) retrieved, generate pregnancy (fertile) (infertile), controlling maternal age. Participants/materials, setting, methods RNA was isolated seminal fluid (21,855 genes). A > 1 absolute log2fold change P<0.0005 considered significant. Transcriptomic compared between (-)Sperm (+)Sperm cohorts. For genetic assessment, spermatozoal DNA obstructive (OA) control 19) cohorts extracted amplified. Gene mutation profiles, detected CLC Genomic Server 9.0, assessed cohort ICSI outcomes, OA-control. Main results role chance analyses plasma 23 8 imbalanced genes, involved (TMCO5B,C10orf62,SMKR1,SPZ1), function (NEU1,TPTE2), testis development (TRPC1,IGSF11-AS1). TPTE2 almost completely expressed 81.8%(9/11) (paternal age, 37.1±6yrs), IGSF11-AS1 underexpressed all 12 34.3±5yrs). Both genes are implicated spermatogenic defects normally highly testis. Interestingly, NEU1, localized acrosome crucial capacitation, exclusively overexpressed matched OA patients 36.8±7yrs). Spermatozoa study displayed transcription (POLR2L), apoptosis (AP5M1), spermiogenic functions (AP1S2,AP1G2,APOE), unaffected When (maternal 36.8±2yrs, paternal 37.1±6yrs) found that fertile patients, term pregnancies, consistent mild MPIG6B (stem cell lineage differentiation) gametes 3 infertile counterparts carried severe (MBD5,CCAR1,PMEPA1,POLK,REC8,REPIN1,MAPRE3,ARL4C) early embryonic development, therefore failed achieve implantation. Limitations, reasons caution Although predicted, men, presence characterized through profiling, preliminary need validation larger cohort. Moreover, although controlled for, confounding female factor cannot undoubtfully excluded. Wider implications findings Epigenetic biomarkers capable predicting spermatogenesis, sparing unnecessary surgery. profiling supporting laying groundwork precision medicine male infertility screening. Trial registration number n/a