P-028 Loss of the m6A methyltransferase METTL5 impairs spermiogenesis and male fertility

Abstract Study question Whether and how METTL5 regulates germ cell development during spermatogenesis. Summary answer is required for spermiogenesis. Loss of resulted in teratozoospermia male infertility via reduced translation acrosome flagellum formation proteins. What known already The roles m6A modifications on mRNA spermatogenesis have been extensively studied. It was reported that knockout mice showed the brain defect sterility 16-week mice. However, detailed mechanism affecting fertility remains elusive. design, size, duration Mettl5 KO were kindly gifted from Prof. Shuibin Lin First Affiliated Hospital Sun Yat-sen University. Heterozygotes used to generate homozygous phenotype assessed. Ribosomal sequencing, proteomics analysis further validation protein performed explore mechanism. Participants/materials, setting, methods Fertility assessment, sperm parameter analyses, nuclear morphology analysis, Transmission electron microscopy (TEM), tissue Collection histological extraction western blot immunofluorescence studies, cDNA synthesis qRT-PCR, vitro fertilization (IVF) this study. Main results role chance Here we methyltransferase-like 5 (METTL5) involved spermiogenesis as a methyltransferase mediating modification rRNA. infertile with teratozoospermia. head absent motility. Furthermore, ability IVF experiment failed. Mechanistically, level rRNA significantly decreased testes translational efficiency levels proteins such FSIP2, ODF2, GK2, PGK2, AKAP4 when depleted. Limitations, reasons caution mutation patient not examined present study Wider implications findings also regulating by METTL5. This highlights critical epigenetic provides novel theoretical explanations modifications. Trial registration number Not applicable