The cause of asthenozoospermia(AZS)is not well understood because of its complexity and heterogeneity.Although some gene mutations have been identified as contributing factors,they are only responsible for a small num...The cause of asthenozoospermia(AZS)is not well understood because of its complexity and heterogeneity.Although some gene mutations have been identified as contributing factors,they are only responsible for a small number of cases.Radial spokes(RSs)are critical for adenosine triphosphate-driven flagellar beating and axoneme stability,which is essential for flagellum motility.In this study,we found novel compound heterozygous mutations in leucine-rich repeat-containing protein 23(LRRC23;c.1018C>T:p.Q340X and c.881_897 Del:p.R295Gfs*32)in a proband from a nonconsanguineous family with AZS and male infertility.Diff-Quik staining and scanning electron microscopy revealed no abnormal sperm morphology.Western blotting and immunofluorescence staining showed that these mutations suppressed LRRC23 expression in sperm flagella.Additionally,transmission electron microscopy showed the absence of RS3 in sperm flagella,which disrupts stability of the radial spoke complex and impairs motility.Following in vitro fertilization and embryo transfer,the proband’s spouse achieved successful pregnancy and delivered a healthy baby.In conclusion,our study indicates that two novel mutations in LRRC23 are associated with AZS,but successful fertility outcomes can be achieved by in vitro fertilization-embryo transfer techniques.展开更多
基金supported by the National Key Research and Development Program of China(No.2022YFC2702702)National Natural Science Foundation of China(No.32270899 and No.32070842)+2 种基金the Natural Science Foundation of Jiangsu Province(No.BK20230004)Young and Middle-Aged Key Personnel Training Project of the Fujian Provincial Health Commission(2019-ZQN-62)Fujian Provincial Finance Project(BPB-TSX2021).
文摘The cause of asthenozoospermia(AZS)is not well understood because of its complexity and heterogeneity.Although some gene mutations have been identified as contributing factors,they are only responsible for a small number of cases.Radial spokes(RSs)are critical for adenosine triphosphate-driven flagellar beating and axoneme stability,which is essential for flagellum motility.In this study,we found novel compound heterozygous mutations in leucine-rich repeat-containing protein 23(LRRC23;c.1018C>T:p.Q340X and c.881_897 Del:p.R295Gfs*32)in a proband from a nonconsanguineous family with AZS and male infertility.Diff-Quik staining and scanning electron microscopy revealed no abnormal sperm morphology.Western blotting and immunofluorescence staining showed that these mutations suppressed LRRC23 expression in sperm flagella.Additionally,transmission electron microscopy showed the absence of RS3 in sperm flagella,which disrupts stability of the radial spoke complex and impairs motility.Following in vitro fertilization and embryo transfer,the proband’s spouse achieved successful pregnancy and delivered a healthy baby.In conclusion,our study indicates that two novel mutations in LRRC23 are associated with AZS,but successful fertility outcomes can be achieved by in vitro fertilization-embryo transfer techniques.
