The Functional Study Of SUN3 In Mice Sperm Head Shaping

Mammalian male gametes are produced through spermatogenesis.The basic process of spermatogenesis is:Spermatogonial stem cells in testis undergo self-renewal and asymmetric mitosis to differentiate into spermatogonial cells.Spermatogonial cells gradually differentiate into spermatocytes via multiple rounds of mitotic proliferation.By meiosis spermatocytes give rise to haploid spermatids,which are finally transformed into sperm by spermiogenesis.It is estimated that more than 2,300 genes are involved in spermatogenesis,but the specific molecular mechanisms of spermatogenesis have not been fully elucidated.To disclose the new genes'function and reveal the molecular mechanisems of spermatogenesis by study new genes implicated in spermatogenesis are important for deepening the understanding of mammalian spermatogenesis and even to male reproductive health.During spermatogenesis in mice,the haploid spermatids will go through a series of complex changes thoroughly,including acrosome formation,sperm head shaping,nucleus condensation and flagellum formation.This process is called spermiogenesis.The elongated spermatozoa then leave the lumen of seminiferous tubule passing through the efferent ductules,the epididymis,finally arrive and store at the epididymis cauda.During mouse spermiogenesis,one of the most obvious changes of spermatids is the transformation of nucleus from a rounnd spherical shape to an elongated hook-liked shape.It has been reported that a variety of mouse models with abnormal head morphology are infertile,suggesting that normal head morphology is an important prerequisite for normal sperm function.However,the specific molecular mechanisms of sperm head shaping are still unclear.CRISPR/Cas9 technology was applied in this study to generate a mouse model that affects sperm head shaping:the Sun3(Sad-1/UNC-84 domain containing 3)knockout mouse.Deletion of Sun3 resulted in male infertility because of reduction in sperm counting and abnormal sperm morphology while female mice was fertile.Most of the acrosome displayed abnormal shape with some were even went missing.The tail of sperm also showed defects in midpiece.When the round spermatids were transformed into the elonaged spermatids,the nuclei were deformed without a typical h ook-like structure which resembles the globozoospermia phenotype.The occurrence of apoptosis increased and the manchette could not assemble in Sun3 knockout mice spermatids.In summary,these results showed that SUN3 is implicated in the regulation of sperm head shaping by controlling the assembly of manchette.These findings provide a new explanation for the production of abnormal sperm.