ECEESPE2025 Poster Presentations Reproductive and Developmental Endocrinology (93 abstracts)
1Copenhagen University Hospital - Rigshospitalet, Blegdamsvej 9, DK-2100, Copenhagen, Denmark, Department of Growth & Reproduction, Copenhagen, Denmark; 2Faculty of Health and Medical Sciences, University of Copenhagen, Department of Cellular and Molecular Medicine, Copenhagen, Denmark; 3International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health, Denmark, Department of Growth & Reproduction, Copenhagen, Denmark; 4Department of Urology, Copenhagen University Hospital Herlev and Gentofte, Herlev, Denmark; 5Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
JOINT1057
Background: Small non-coding RNAs (sncRNAs) are found in circulation and are effective disease biomarkers. Some sncRNAs are actively secreted into circulation and may carry an endocrine signal to target tissues. Here, we identify circulating sncRNAs originating from the testis by mapping circulating sncRNAs before and after castration.
Methods: A cohort of 57 men with prostate cancer were randomised to either subcapsular orchiectomy (O-arm, n = 28) or GnRH-analogue (G-arm, n = 29) as part of a previous study. Blood samples were taken at baseline (W0), 12 weeks (W12), and 24 weeks (W24). RNA from 169 longitudinally paired serum samples was isolated and sequenced using the RealSeq-Biofluids Small RNA library preparation kit and sequenced on an Illumina NextSeq 550. Data from samples of suboptimal quality (n = 5) were excluded.
Results: JOINT analysis of sncRNA reads at W12 and W24 in contrast to W0 identified 81 and 175 circulating sncRNAs that were present at significantly different levels in the O-arm and G-arm, respectively. Most sncRNAs were found in lower levels (67 and 150 in the O- and G-arm, respectively) and only a few at higher levels (14 and 25 in the O- and G-arm, respectively). The most prevalent type of sncRNA identified to be differentially present after castration was piRNAs contributing to 44% (36 piRNAs) in the O-arm and 58% (101 piRNAs) in the G-arm. We identified 16 sncRNAs that were differentially present in both the O- and G-arm. Of the 16 overlapping sncRNAs, 5 have previously been reported in RNAseq from the testes and 8 (50%) were piRNAs, indicating that a testicular origin is likely.
Discussion: We identified several circulating sncRNAs that were significantly altered in serum from men after castration. The sncRNAs likely originate from the testis and could be novel markers of testicular function that potentially carry an endocrine message. However, the study was based on older men with prostate cancer who likely did not possess optimal testicular function at baseline, and we cannot rule out confounding effects from the treatment of prostate cancer.