P-027 Absence of perinuclear theca ACTRT1 protein induces sperm head deformation and primary male infertility in humans

Abstract Study question Given that Actrt1 knockout induces teratospermia, fertilization failure and severe male infertility in mice, will ACTRT1 deficiency affect sperm morphology fertility humans? Summary answer The ∼110 kb microdeletion of X chromosome only including gene was identified inducing head deformation an infertile Chinese man. What is known already actin-related proteins, ACTRT1, ACTRT2, ACTL7A, ACTL9, interact to form a multimeric complex the subacrosomal region vital for attachment acrosome nucleus. disruption ACTL7A or ACTL9 have been cause acrosomal detachment, total humans mice. Actrt1-knockout mice are severely subfertile also because malformed heads with detached acrosomes partial fertilization. Loss/reduced expression and/or abnormal localization PLCζ, well-known sperm-borne activating factor, ACTL7A/ACTL9 mutant patients as well Actrt1-, Actl7a-, Actl9-deficient design, size, duration We recruited cohort 85 men teratospermia which characterized by deformed center reproductive medicine from August 2019 June 2022. Genomic DNA (gDNA) extracted peripheral blood, then whole-exome sequencing silico analyses were performed identify mutations. Morphological analysis, functional assays, assisted therapy Participants/materials, setting, methods confirmed whole-genome sequencing, PCR qPCR. Family members’ gDNA collected define hereditary mode. Papanicolaou-staining, scanning transmission electronic microscopy reveal morphologies. Western blot immunostaining spermatozoa conducted explore pathological mechanism deficiency. Intracytoplasmic injection (ICSI) combined artificial oocyte activation (AOA) applied ACTRT1-deletion patient. Main results role chance whole-gene deletion mutation on Chromosome inherited his mother. microscopy, showed owing mimicked previously reported phenotype western suggested induced down-regulated PLCζ but not human samples. both patient, could be effectively rescued ICSI AOA. Limitations, reasons caution Additional cases needed confirm genetic contribution mutations failure. In addition, proband oligozoospermia mild asthenozoospermia. effect count motility still need more investigation. Wider implications findings Our gene–disease relationship between This report describe good outcome AOA ACTRT1-deficient Trial registration number applicable