Essential role for SUN5 in anchoring sperm head to the tail

Abstract

SUN (Sad1 and UNC84 domain containing)-domain proteins are reported to reside on the nuclear membrane playing distinct roles in nuclear dynamics. SUN5 is a new member of the SUN family, with little knowledge regarding its function. Here, we generated Sun5−/− mice and found that male mice were infertile. Most Sun5-null spermatozoa displayed a globozoospermia-like phenotype but they were actually acephalic spermatozoa. Additional studies revealed that SUN5 was located in the neck of the spermatozoa, anchoring sperm head to the tail, and without functional SUN5 the sperm head to tail coupling apparatus was detached from nucleus during spermatid elongation. Finally, we found that healthy heterozygous offspring could be obtained via intracytoplasmic injection of Sun5-mutated sperm heads for both male mice and patients. Our studies reveal the essential role of SUN5 in anchoring sperm head to the tail and provide a promising way to treat this kind of acephalic spermatozoa-associated male infertility.

Loss‐of‐function mutations in centrosomal protein 112 is associated with human acephalic spermatozoa phenotype

“…Deletion of SUN5 did not impact the formation of HTCA, but HTCA was separated from implantation fossa at the beginning of sperm deformation, resulting in acephalic spermatozoa. 23,29 Zhu et al reported that 72.00% (18/25) of their acephalic spermatozoa cohort is caused by SUN5 and PMFBP1 mutations, suggesting that other gene mutations are also involved in the development of acephalic spermatozoa. 16 In previous studies, we have reported that the mutations in SUN5, TSGA10 and BRDT may result in acephalic spermatozoa in human.…”

The dynamics of gene expression during and post meiosis sets the sperm agenda

“…Rapgef6‐KO mice have small, atrophied, hypospermatogenic testes, and their epididymal sperm have low‐motility with inhibited fertilizing ability (K. Okada et al, ). Sun5 anchors sperm head to the tail and Sun −/− male mice are infertile with sperm having heads separated from tails and without chromatin and acrosome (Y. Shang et al, ). On the other hand, Setd2 (SET domain–containing 2) is the major histone methyltransferase that has important function in embryonic stem cell differentiation and in spermiogenesis.…”

“…. Sun5 anchors sperm head to the tail and Sun −/− male mice are infertile with sperm having heads separated from tails and without chromatin and acrosome (Y Shang et al, 2017)…”

Nuclear envelope dynamics during mammalian spermatogenesis: new insights on male fertility

“…Furthermore, there is growing evidence that mutations in human genes encoding NE proteins can have deleterious effects on the development of fertilization‐competent spermatozoa and lead to severe infertility phenotypes in men (Zhu et al ., , ). A correlation between spermatogenesis‐specific NE dynamics and male fertility is also supported by several knockout mouse models (Alsheimer et al ., ; Ding et al ., ; Pierre et al ., ; Horn et al ., ; Link et al ., ; Pasch et al ., ; Chen et al ., ; Shang et al ., ). Despite considerable advances in the field, an integrative analysis of the available scientific data regarding the involvement of NE proteins in the successful progression of male meiosis and spermiogenesis has never been presented.…”

“…In recent decades, numerous studies have demonstrated that spermatogenesis requires extensive rearrangement of the NE network, including the composition of its specific proteome and the localization of these proteins. Interestingly, the list of NE proteins restricted to or highly enriched in mammalian male germline cells is rapidly increasing, comprising a total of 10 NE components at present (Furukawa, Inagaki & Hotta, ; Schutz et al ., ; Gob et al ., ; Morimoto et al ., ; Pierre et al ., ; Pasch et al ., ; Chen et al ., ; Shang et al ., ; Elkhatib et al ., ). Furthermore, there is growing evidence that mutations in human genes encoding NE proteins can have deleterious effects on the development of fertilization‐competent spermatozoa and lead to severe infertility phenotypes in men (Zhu et al ., , ).…”