OR26-08 Temporal Expression and Cellular Localization of DHX37 in Human Gonadal Development: Insights from Single-Cell RNA Sequencing

Abstract Disclosure: J.M. Marques: None. R.L. Batista: None. S. Domenice: None. B.B. Mendonca: None. The DEAD-box helicase 37 (DHX37) is implicated in various cellular processes, including RNA metabolism and ribosome biogenesis. DHX37 pathogenic allelic variants have been associated with differences of sexual development, 46, XY DSD, however, its role in human gonadal development remains unexplored. This study investigates the temporal expression patterns and cellular localization of DHX37 in human gonads during development, utilizing publicly available single-cell RNA sequencing datasets (scRNA). We analyzed scRNA from public datasets: GSE256162, GSE86146, and GSE167860, comprising human gonadal tissues. Data processing and analysis were conducted using R software, version 2023.12.1+402. Temporal expression of DHX37 was assessed across different early developmental stages (4 to 37 weeks of gestational age) and later stages (5 to 12 years old), with a focus on identifying the peak expression period. Cell clustering analysis was performed to determine the specific gonadal cell types expressing DHX37. Additionally, differential gene expression analysis was conducted on DHX37-positive cells to identify enriched biological processes. DHX37 expression peaked at the fourth week of human gonadal development (16.87-fold higher than all other time points) and was subsequently downregulated after 21 weeks. Clustering analysis revealed that DHX37 is expressed in Leydig and Sertoli cells, with the highest expression observed in supporting and myoid cells of the testis. Differential expression analysis of DHX37-positive cells identified significant enrichment in biological processes such as male meiotic nuclear division, piRNA processing, retrotransposon silencing, cellular processes involved in reproduction in multicellular organisms, positive regulation of reproductive processes, retrotransposition, and transposition. Our findings suggest that DHX37 plays a critical role in early human gonadal development, particularly in supporting and myoid cells. The enrichment of DHX37 in processes related to meiosis and transposon silencing indicates its potential involvement in maintaining genomic integrity during germ cell development. Further studies are warranted to elucidate the specific mechanisms by which DHX37 contributes to human reproductive development. Presentation: Monday, July 14, 2025